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Tang SS, Zhao XF, An XD, Sun WJ, Kang XM, Sun YT, Jiang LL, Gao Q, Li ZH, Ji HY, Lian FM. Classification and identification of risk factors for type 2 diabetes. World J Diabetes 2025; 16:100371. [PMID: 39959280 PMCID: PMC11718467 DOI: 10.4239/wjd.v16.i2.100371] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Revised: 10/24/2024] [Accepted: 11/26/2024] [Indexed: 12/30/2024] Open
Abstract
The risk factors for type 2 diabetes mellitus (T2DM) have been increasingly researched, but the lack of systematic identification and categorization makes it difficult for clinicians to quickly and accurately access and understand all the risk factors, which are categorized in this paper into five categories: Social determinants, lifestyle, checkable/testable risk factors, history of illness and medication, and other factors, which are discussed in a narrative review. Meanwhile, this paper points out the problems of the current research, helps to improve the systematic categorisation and practicality of T2DM risk factors, and provides a professional research basis for clinical practice and industry decision-making.
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Affiliation(s)
- Shan-Shan Tang
- College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130117, Jilin Province, China
| | - Xue-Fei Zhao
- Department of Endocrinology, Guang’anmen Hospital, Beijing 100053, China
| | - Xue-Dong An
- Department of Endocrinology, Guang’anmen Hospital, Beijing 100053, China
| | - Wen-Jie Sun
- Department of Endocrinology, Guang’anmen Hospital, Beijing 100053, China
| | - Xiao-Min Kang
- Department of Endocrinology, Guang’anmen Hospital, Beijing 100053, China
| | - Yu-Ting Sun
- Department of Endocrinology, Guang’anmen Hospital, Beijing 100053, China
| | - Lin-Lin Jiang
- Department of Endocrinology, Guang’anmen Hospital, Beijing 100053, China
| | - Qing Gao
- Department of Endocrinology, Guang’anmen Hospital, Beijing 100053, China
| | - Ze-Hua Li
- Department of Endocrinology, Guang’anmen Hospital, Beijing 100053, China
| | - Hang-Yu Ji
- Department of Endocrinology, Guang’anmen Hospital, Beijing 100053, China
| | - Feng-Mei Lian
- Department of Endocrinology, Guang’anmen Hospital, Beijing 100053, China
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Hwang HB, Yoon S, Hong KY. Nevus lipomatosus superficialis mimicking ectopic breast tissue: A rare case report. Medicine (Baltimore) 2025; 104:e41339. [PMID: 39928803 PMCID: PMC11813040 DOI: 10.1097/md.0000000000041339] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Revised: 12/31/2024] [Accepted: 01/07/2025] [Indexed: 02/12/2025] Open
Abstract
RATIONALE Diagnosis of solitary superficial lipomatous mass may vary depending on circumstances. Although preliminary diagnosis can be made through clinical symptoms and imaging studies, final diagnosis can change through histological examination. This is the first reported case of nevus lipomatosus superficialis (NLS) resembling ectopic breast tissue which may provide valuable insights for clinicians managing similar lesions. PATIENT CONCERNS A 41-year-old female had a solitary mass on her left lower flank, lasting more than 10 years with cyclic pain corresponding to her menstrual cycle. DIAGNOSES A computed tomography scan suggested benign subcutaneous lipoma, but histopathological examination after surgery confirmed the diagnosis of NLS. INTERVENTIONS Surgical excision was performed without complications. OUTCOMES No regrowth of the lipomatous mass was observed at the 6-month follow-up, and there was no recurrence of cyclic pain. LESSONS This report aims to discuss an unusual presentation of NLS that mimics ectopic breast tissue and causes cyclic pain related to the menstrual cycle. Understanding this case provides insights into the potential hormonal influence on focal adipose tumors and the challenges in differential diagnosis.
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Affiliation(s)
- Hui Beom Hwang
- Department of Plastic and Reconstructive Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Sehoon Yoon
- Department of Plastic and Reconstructive Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Ki Yong Hong
- Department of Plastic and Reconstructive Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
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Tondo P, Meschi C, Mantero M, Scioscia G, Siciliano M, Bradicich M, Stella GM. Sex and gender differences during the lung lifespan: unveiling a pivotal impact. Eur Respir Rev 2025; 34:240121. [PMID: 39971394 PMCID: PMC11836673 DOI: 10.1183/16000617.0121-2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2024] [Accepted: 10/29/2024] [Indexed: 02/21/2025] Open
Abstract
Sex and gender differences significantly influence lung parenchyma development, beginning as early as the embryonic stages of human life. Although this association is well known in the clinical manifestations of some relevant pulmonary diseases, there is less data available regarding their effects on cell biological programmes across different stages of body development. A deep understanding of these mechanisms could help in defining preventive strategies tailored to a fully personalised approach to respiratory medicine. From this perspective, this review aims to analyse the influence of sex and gender on bronchoalveolar and vascular compartments from embryonic and neonatal stages through to adolescence, adulthood and elder age.
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Affiliation(s)
- Pasquale Tondo
- Department of Medical and Surgical Sciences, University of Foggia; Respiratory and Critical Care Unit, Polyclinic Foggia University-Hospital, Foggia, Italy
| | - Claudia Meschi
- Department of Surgical, Medical, Molecular and Critical Area Pathology, University of Pisa, Pisa, Italy
- Pulmonary Unit, Cardiothoracic and Vascular Department, Pisa University Hospital, Pisa, Italy
| | - Marco Mantero
- Department of Health Sciences, Respiratory Unit, ASST Santi Paolo e Carlo, San Paolo Hospital, University of Milan, Milan, Italy
| | - Giulia Scioscia
- Department of Medical and Surgical Sciences, University of Foggia; Respiratory and Critical Care Unit, Polyclinic Foggia University-Hospital, Foggia, Italy
| | - Matteo Siciliano
- Catholic University of the Sacred Heart, Rome Campus; Agostino Gemelli IRCCS University Polyclinic Foundation, Rome, Italy
| | - Matteo Bradicich
- Department of Pulmonology, University Hospital Zurich, Zurich, Switzerland
| | - Giulia M. Stella
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia, Italy
- Cardiothoracic and Vascular Department, Unit of Respiratory Diseases, IRCCS San Matteo Polyclinic Hospital, Pavia, Italy
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Güçlü-Geyik F, Erginel T, Güleç Ç, Köseoğlu-Büyükkaya P, Erginel-Ünaltuna N. Methylation of the ESR1 promoters in visceral adipose tissue and its relationship with obesity. Mol Biol Rep 2024; 51:1144. [PMID: 39531130 DOI: 10.1007/s11033-024-10091-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Accepted: 11/01/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND Obesity is associated with decreased ESR1 expression level in visceral adipose tissue. However, it is unclear exactly what mechanisms are responsible for this decline. The aim of this study was to investigate the impact of aberrant methylation of the ESR1 alternative promoters on decreased ESR1 expression and its connection to obesity. METHODS Visceral adipose tissues and peripheral blood cells were obtained from 21 patients (non-obese and obese) undergoing inguinal hernia or gallbladder removal. Alternative promoter regions, C, E2 and F of the ESR1 gene, were analyzed by Methylation-Specific PCR (MSP) and mRNA levels were measured by quantitative real-time PCR (qPCR) in both visceral adipose tissue and peripheral blood cells. All statistical analyses were performed by SPSS (23.0). RESULTS The methylation percentage in the three promoter regions of ESR1 was not different in obese individuals compared to non-obese individuals. We observed that promoter C had the highest methylation frequency in obese patients, although it was not statistically significant. Additionally, we observed that the hypermethylation of ESR1's promoter C was significantly associated with lower mRNA expression level in obesity (p = 0.020). CONCLUSION This study suggests that methylation of ESR1 promoter C may be a factor in the development of obesity or a consequence of obesity. Further studies with advanced methods and larger study groups are needed to clarify this issue.
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Affiliation(s)
- Filiz Güçlü-Geyik
- Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.
- Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Vakif Gureba Cad, 34080, Sehremini, Istanbul, Turkey.
| | - Turgay Erginel
- Department of General Surgery, Istanbul Training and Research Hospital, Istanbul, Turkey
| | - Çağrı Güleç
- Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey
| | - Pınar Köseoğlu-Büyükkaya
- Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey
| | - Nihan Erginel-Ünaltuna
- Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey
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Ledesma-Aparicio J, Mailloux-Salinas P, Arias-Chávez DJ, Campos-Pérez E, Calixto-Tlacomulco S, Cruz-Rangel A, Reyes-Grajeda JP, Bravo G. Transcriptomic Analysis of the Protective Effect of Piperine on Orlistat Hepatotoxicity in Obese Male Wistar Rats. J Biochem Mol Toxicol 2024; 38:e70040. [PMID: 39503200 DOI: 10.1002/jbt.70040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Revised: 05/17/2024] [Accepted: 10/18/2024] [Indexed: 11/08/2024]
Abstract
Obesity is a risk factor for the development of noncommunicable diseases that impair the quality of life. Orlistat is one of the most widely used drugs in the management of obesity due to its accessibility and low cost. However, cases of hepatotoxicity have been reported due to the consumption of this drug. On the other hand, piperine is an alkaloid found in black pepper that has demonstrated antiobesity, antihyperlipidemic, antioxidant, prebiotic, and hepatoprotective effects. The aim of this study was to evaluate the protective effect of piperine on the toxicity of orlistat in liver tissue. Obese male rats were administered piperine (30 mg/kg), orlistat (60 mg/kg), and the orlistat-piperine combination (30 mg/kg + 60 mg/kg) daily for 6 weeks. It was observed that the orlistat-piperine treatment resulted in greater weight loss, decreased biochemical markers (lipid profile, liver enzymes, pancreatic lipase activity), and histopathological analysis showed decreased hepatic steatosis and reduction of duodenal inflammation. Transcriptomic analysis revealed that the administration of piperine with orlistat increased the expression of genes related to the beta-oxidation of fatty acids, carbohydrate metabolism, detoxification of xenobiotics, and response to oxidative stress. Therefore, the results suggest that the administration of orlistat-piperine activates signaling pathways that confer a hepatoprotective effect, reducing the toxic impact of this drug.
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Affiliation(s)
- Jessica Ledesma-Aparicio
- Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados del IPN, Mexico City, Mexico
| | - Patrick Mailloux-Salinas
- Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados del IPN, Mexico City, Mexico
| | - David Julian Arias-Chávez
- Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados del IPN, Mexico City, Mexico
| | - Elihu Campos-Pérez
- Departamento de Patología, Hospital General Dra Matilde Petra Montoya Lafragua, ISSSTE, Mexico City, Mexico
| | - Sandra Calixto-Tlacomulco
- Laboratorio de Estructura de Proteínas, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico
| | - Armando Cruz-Rangel
- Laboratorio de Estructura de Proteínas, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico
| | - Juan Pablo Reyes-Grajeda
- Laboratorio de Estructura de Proteínas, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico
| | - Guadalupe Bravo
- Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados del IPN, Mexico City, Mexico
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Jiang Y, Yu T, Fan J, Guo X, Hua H, Xu D, Wang Y, Yan CH, Xu J. Longitudinal associations of social jetlag with obesity indicators among adolescents - Shanghai adolescent cohort. Sleep Med 2024; 121:171-178. [PMID: 38991425 DOI: 10.1016/j.sleep.2024.07.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Revised: 06/17/2024] [Accepted: 07/03/2024] [Indexed: 07/13/2024]
Abstract
OBJECTIVE To explore the longitudinal association between social-jetlag (SJL) and obesity development among adolescents, sex-difference and related modifying factors in the association. METHODS Based on Shanghai-Adolescent-Cohort during 2017-2021, a total of 609 students were investigated. In grade 6, 7 and 9, the information on SJL was collected using questionnaires, and anthropometric measures were conducted. The fingernail cortisol and progesterone levels in grade 6 (using LC-MS/MS) and body composition in grade 9 (using Inbody-S10) were measured. By the latent-class-mixture-modeling, two trajectories for SJL (high-level vs. low-level) throughout 4 years were developed. The prospective associations of SJL trajectories and weight/fat gains were analyzed by sex and under different (high/moderate/low) cortisol/progesterone stratifications. RESULTS In grades 6-9, 39.00%-44.50 % of adolescents experienced at least 1 h of SJL. Compared with the low-level SJL trajectory, the high-level SJL trajectory was associated with greater differences in body-mass-index Z-scores and waist-to-height ratios across 4 years, higher levels of body-fat-percentage and fat-mass-index in grade 9 (P-values<0.05), and such associations were stronger among girls and under moderate-to-high (vs. low) baseline cortisol and progesterone levels. However, no significant associations among boys were observed. CONCLUSIONS High-level SJL in adolescents may be associated with the development of obesity, especially among adolescent girls and under relatively high baseline cortisol and progesterone levels.
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Affiliation(s)
- Yining Jiang
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China
| | - Ting Yu
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China
| | - Jue Fan
- Department of Children's Healthcare, MOE-Shanghai Key Lab of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Changning Maternity & Infant Health Institute, Shanghai, China
| | - Xiangrong Guo
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China
| | - Hui Hua
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China
| | - Dongqing Xu
- Institute of Higher Education, Fudan University, Shanghai, China
| | - Yuefen Wang
- Shanghai Municipal Education Commission Department, Shanghai, China
| | - Chong-Huai Yan
- Department of Children's Healthcare, MOE-Shanghai Key Lab of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jian Xu
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China; Department of Children's Healthcare, MOE-Shanghai Key Lab of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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Lu W, Li S, Li Y, Zhou J, Wang K, Chen N, Li Z. Associations of sex-related and thyroid-related hormones with risk of metabolic dysfunction-associated fatty liver disease in T2DM patients. BMC Endocr Disord 2024; 24:84. [PMID: 38849804 PMCID: PMC11161932 DOI: 10.1186/s12902-024-01618-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Accepted: 05/31/2024] [Indexed: 06/09/2024] Open
Abstract
BACKGROUND We aimed to examine sex-specific associations between sex- and thyroid-related hormones and the risk of metabolic dysfunction-associated fatty liver disease (MAFLD) in patients with type 2 diabetes mellitus (T2DM). METHODS Cross-sectional analyses of baseline information from an ongoing cohort of 432 T2DM patients (185 women and 247 men) in Xiamen, China were conducted. Plasma sex-related hormones, including estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), progesterone, and total testosterone (TT), and thyroid-related hormones, including free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), and parathyroid hormone (PTH), were measured using chemiluminescent immunoassays. MAFLD was defined as the presence of hepatic steatosis (diagnosed by either hepatic ultrasonography scanning or fatty liver index (FLI) score > 60) since all subjects had T2DM in the present study. RESULTS Prevalence of MAFLD was 65.6% in men and 61.1% in women with T2DM (P = 0.335). For men, those with MAFLD showed significantly decreased levels of FSH (median (interquartile range (IQR)):7.2 (4.9-11.1) vs. 9.8 (7.1-12.4) mIU/ml) and TT (13.2 (10.4-16.5) vs. 16.7 (12.8-21.6) nmol/L) as well as increased level of FT3 (mean ± standard deviation (SD):4.63 ± 0.68 vs. 4.39 ± 0.85 pmol/L) than those without MAFLD (all p-values < 0.05). After adjusting for potential confounding factors, FSH and LH were negative, while progesterone was positively associated with the risk of MAFLD in men, and the adjusted odds ratios (ORs) (95% confidence intervals (CIs)) were 0.919 (0.856-0.986), 0.888 (0.802-0.983), and 8.069 (2.019-32.258) (all p-values < 0.05), respectively. In women, there was no statistically significant association between sex- or thyroid-related hormones and the risk of MAFLD. CONCLUSION FSH and LH levels were negative, whereas progesterone was positively associated with the risk of MAFLD in men with T2DM. Screening for MAFLD and monitoring sex-related hormones are important for T2DM patients, especially in men.
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Affiliation(s)
- Weihong Lu
- Department of Gynecology, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China
- Xiamen Clinical Research Center for Cancer Therapy, Xiamen, China
| | - Shangjian Li
- Department of Endocrinology, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China
| | - Yuhua Li
- School of Mechanics and Civil Engineering, China University of Mining & Technology- Beijing, Beijing, China
| | - Jingqi Zhou
- Department of Endocrinology, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China
| | - Kai Wang
- Department of Endocrinology, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China
| | - Ning Chen
- Department of Endocrinology, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China.
| | - Zhibin Li
- Epidemiology Research Unit Translational Medicine Research Center, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, No.55 Zhenhai Road, Xiamen, 361003, China.
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Toubon G, Butel MJ, Rozé JC, Delannoy J, Ancel PY, Aires J, Charles MA. Association between gut microbiota at 3.5 years of age and body mass index at 5 years: results from two French nationwide birth cohorts. Int J Obes (Lond) 2024; 48:503-511. [PMID: 38097759 DOI: 10.1038/s41366-023-01442-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Revised: 11/26/2023] [Accepted: 12/01/2023] [Indexed: 04/02/2024]
Abstract
BACKGROUND/OBJECTIVES The relationship between gut microbiota and changes in body mass index (BMI) or pediatric overweight in early life remains unclear, and information regarding the preterm population is scarce. This study aimed to investigate how the gut microbiota at 3.5 years of age is associated with (1) later BMI at 5 years, and (2) BMI z-score variations between 2 and 5 years in children from two French nationwide birth cohorts. SUBJECTS/METHODS Bacterial 16S rRNA gene sequencing was performed to profile the gut microbiota at 3.5 years of age in preterm children (n = 143, EPIPAGE 2 cohort) and late preterm/full-term children (n = 369, ELFE cohort). The predicted abundances of metabolic functions were computed using PICRUSt2. Anthropometric measurements were collected at 2 and 5 years of age during medical examinations or retrieved from children's health records. Statistical analyses included multivariable linear and logistic regressions, random forest variable selection, and MiRKAT. RESULTS The Firmicutes to Bacteroidetes (F/B) ratio at 3.5 years was positively associated with the BMI z-score at 5 years. Several genera were positively ([Eubacterium] hallii group, Fusicatenibacter, and [Eubacterium] ventriosum group) or negatively (Eggerthella, Colidextribacter, and Ruminococcaceae CAG-352) associated with the BMI z-scores at 5 years. Some genera were also associated with variations in the BMI z-scores between 2 and 5 years of age. Predicted metabolic functions, including steroid hormone biosynthesis, biotin metabolism, glycosaminoglycan degradation, and amino sugar and nucleotide sugar metabolism, were associated with lower BMI z-scores at 5 years. The unsaturated fatty acids biosynthesis pathway was associated with higher BMI z-scores. CONCLUSIONS These findings indicate that the gut microbiota at 3.5 years is associated with later BMI during childhood, independent of preterm or term birth, suggesting that changes in the gut microbiota that may predispose to adult obesity begin in early childhood.
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Affiliation(s)
- Gaël Toubon
- Université Paris Cité et Université Sorbonne Paris Nord, Inserm, INRAE, Centre de Recherche en Épidémiologie et StatistiqueS (CRESS), F-75004, Paris, France
- Université Paris Cité, INSERM, UMR-S 1139, Physiopathologie et Pharmacotoxicologie Placentaire Humaine Microbiote Pré & Postnatal (3PHM), F-75006, Paris, France
- FHU PREMA, « Fighting Prematurity », F-75006, Paris, France
| | - Marie-José Butel
- Université Paris Cité, INSERM, UMR-S 1139, Physiopathologie et Pharmacotoxicologie Placentaire Humaine Microbiote Pré & Postnatal (3PHM), F-75006, Paris, France
- FHU PREMA, « Fighting Prematurity », F-75006, Paris, France
| | - Jean-Christophe Rozé
- INRAE, UMR 1280, Physiologie des Adaptations Nutritionnelles (PhAN), Centre d'investigation clinique 1413, Centre hospitalo-universitaire de Nantes, F-44300, Nantes, France
| | - Johanne Delannoy
- Université Paris Cité, INSERM, UMR-S 1139, Physiopathologie et Pharmacotoxicologie Placentaire Humaine Microbiote Pré & Postnatal (3PHM), F-75006, Paris, France
- FHU PREMA, « Fighting Prematurity », F-75006, Paris, France
| | - Pierre-Yves Ancel
- Université Paris Cité et Université Sorbonne Paris Nord, Inserm, INRAE, Centre de Recherche en Épidémiologie et StatistiqueS (CRESS), F-75004, Paris, France
- FHU PREMA, « Fighting Prematurity », F-75006, Paris, France
| | - Julio Aires
- Université Paris Cité, INSERM, UMR-S 1139, Physiopathologie et Pharmacotoxicologie Placentaire Humaine Microbiote Pré & Postnatal (3PHM), F-75006, Paris, France.
- FHU PREMA, « Fighting Prematurity », F-75006, Paris, France.
| | - Marie-Aline Charles
- Université Paris Cité et Université Sorbonne Paris Nord, Inserm, INRAE, Centre de Recherche en Épidémiologie et StatistiqueS (CRESS), F-75004, Paris, France.
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Zhang J, Gu W, Zhai S, Liu Y, Yang C, Xiao L, Chen D. Phthalate metabolites and sex steroid hormones in relation to obesity in US adults: NHANES 2013-2016. Front Endocrinol (Lausanne) 2024; 15:1340664. [PMID: 38524635 PMCID: PMC10957739 DOI: 10.3389/fendo.2024.1340664] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2023] [Accepted: 02/19/2024] [Indexed: 03/26/2024] Open
Abstract
Background Obesity and metabolic syndrome pose significant health challenges in the United States (US), with connections to disruptions in sex hormone regulation. The increasing prevalence of obesity and metabolic syndrome might be associated with exposure to phthalates (PAEs). Further exploration of the impact of PAEs on obesity is crucial, particularly from a sex hormone perspective. Methods A total of 7780 adult participants in the National Health and Nutrition Examination Survey (NHANES) from 2013 to 2016 were included in the study. Principal component analysis (PCA) coupled with multinomial logistic regression was employed to elucidate the association between urinary PAEs metabolite concentrations and the likelihood of obesity. Weighted quartiles sum (WQS) regression was utilized to consolidate the impact of mixed PAEs exposure on sex hormone levels (total testosterone (TT), estradiol and sex hormone-binding globulin (SHBG)). We also delved into machine learning models to accurately discern obesity status and identify the key variables contributing most to these models. Results Principal Component 1 (PC1), characterized by mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) as major contributors, exhibited a negative association with obesity. Conversely, PC2, with monocarboxyononyl phthalate (MCNP), monocarboxyoctyl phthalate (MCOP), and mono(3-carboxypropyl) phthalate (MCPP) as major contributors, showed a positive association with obesity. Mixed exposure to PAEs was associated with decreased TT levels and increased estradiol and SHBG. During the exploration of the interrelations among obesity, sex hormones, and PAEs, models based on Random Forest (RF) and eXtreme Gradient Boosting (XGBoost) algorithms demonstrated the best classification efficacy. In both models, sex hormones exhibited the highest variable importance, and certain phthalate metabolites made significant contributions to the model's performance. Conclusions Individuals with obesity exhibit lower levels of TT and SHBG, accompanied by elevated estradiol levels. Exposure to PAEs disrupts sex hormone levels, contributing to an increased risk of obesity in US adults. In the exploration of the interrelationships among these three factors, the RF and XGBoost algorithm models demonstrated superior performance, with sex hormones displaying higher variable importance.
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Affiliation(s)
- Jiechang Zhang
- Department of Cardiology, Zhuhai People's Hospital (Zhuhai Clinical Medical College of Jinan University), Zhuhai, Guangdong, China
| | - Wen Gu
- Department of Biostatistics, School of Public Health, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Shilei Zhai
- Department of Biostatistics, School of Public Health, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Yumeng Liu
- Department of Biostatistics, School of Public Health, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Chengcheng Yang
- Department of Ophthalmology, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, Guangdong, China
| | - Lishun Xiao
- Department of Biostatistics, School of Public Health, Xuzhou Medical University, Xuzhou, Jiangsu, China
- Center for Medical Statistics and Data Analysis, Xuzhou Medical University, Xuzhou, Jiangsu, China
- Key Laboratory of Human Genetics and Environmental Medicine, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Ding Chen
- School of Medical Information and Engineering, Xuzhou Medical University, Xuzhou, Jiangsu, China
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Rehman A, Lathief S, Charoenngam N, Pal L. Aging and Adiposity-Focus on Biological Females at Midlife and Beyond. Int J Mol Sci 2024; 25:2972. [PMID: 38474226 DOI: 10.3390/ijms25052972] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 02/10/2024] [Accepted: 02/20/2024] [Indexed: 03/14/2024] Open
Abstract
Menopause is a physiological phase of life of aging women, and more than 1 billion women worldwide will be in menopause by 2025. The processes of global senescence parallel stages of reproductive aging and occur alongside aging-related changes in the body. Alterations in the endocrine pathways accompany and often predate the physiologic changes of aging, and interactions of these processes are increasingly being recognized as contributory to the progression of senescence. Our goal for this review is to examine, in aging women, the complex interplay between the endocrinology of menopause transition and post-menopause, and the metabolic transition, the hallmark being an increasing tendency towards central adiposity that begins in tandem with reproductive aging and is often exacerbated post menopause. For the purpose of this review, our choice of the terms 'female' and 'woman' refer to genetic females.
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Affiliation(s)
- Amna Rehman
- Department of Internal Medicine, Berkshire Medical Center, Pittsfield, MA 02101, USA
| | - Sanam Lathief
- Division of Endocrinology, Mount Auburn Hospital, Cambridge, MA 02138, USA
- Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
| | - Nipith Charoenngam
- Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
- Department of Medicine, Mount Auburn Hospital, Cambridge, MA 02138, USA
- Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
| | - Lubna Pal
- Division of Reproductive Endocrinology & Infertility, Department of Obstetrics, Gynecology & Reproductive Sciences, Yale School of Medicine, New Haven, CT 06510, USA
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Abbasi K, Zarezadeh R, Valizadeh A, Mehdizadeh A, Hamishehkar H, Nouri M, Darabi M. White-brown adipose tissue interplay in polycystic ovary syndrome: Therapeutic avenues. Biochem Pharmacol 2024; 220:116012. [PMID: 38159686 DOI: 10.1016/j.bcp.2023.116012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Accepted: 12/22/2023] [Indexed: 01/03/2024]
Abstract
This study highlights the therapeutic potential of activating brown adipose tissue (BAT) for managing polycystic ovary syndrome (PCOS), a prevalent endocrine disorder associated with metabolic and reproductive abnormalities. BAT plays a crucial role in regulating energy expenditure and systemic insulin sensitivity, making it an attractive target for the treatment of obesity and metabolic diseases. Recent research suggests that impaired BAT function and mass may contribute to the link between metabolic disturbances and reproductive issues in PCOS. Additionally, abnormal white adipose tissue (WAT) can exacerbate these conditions by releasing adipokines and nonesterified fatty acids. In this review, we explored the impact of WAT changes on BAT function in PCOS and discussed the potential of BAT activation as a therapeutic strategy to improve PCOS symptoms. We propose that BAT activation holds promise for managing PCOS; however, further research is needed to confirm its efficacy and to develop clinically feasible methods for BAT activation.
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Affiliation(s)
- Khadijeh Abbasi
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Reza Zarezadeh
- Women's Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Amir Valizadeh
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Amir Mehdizadeh
- Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hamed Hamishehkar
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Nouri
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Masoud Darabi
- Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran; Division of Experimental Oncology, Department of Hematology and Oncology, University Medical Center Schleswig-Holstein, Campus Lübeck, Germany.
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Perez-Diaz C, Uriz-Martínez M, Ortega-Rico C, Leno-Duran E, Barrios-Rodríguez R, Salcedo-Bellido I, Arrebola JP, Requena P. Phthalate exposure and risk of metabolic syndrome components: A systematic review. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2024; 340:122714. [PMID: 37844863 DOI: 10.1016/j.envpol.2023.122714] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Revised: 09/13/2023] [Accepted: 10/07/2023] [Indexed: 10/18/2023]
Abstract
Metabolic syndrome is a cluster of conditions that increase the risk of cardiovascular disease, i.e. obesity, insulin resistance, hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL-c) levels and arterial hypertension. Phthalates are environmental chemicals which might influence the risk of the aforementioned disturbances, although the evidence is still controversial. The objective of this work was to synthesize the evidence on the association between human phthalate exposure and metabolic syndrome or any of its components. In this systematic review, the PRISMA guidelines were followed and the literature was search in PubMed, Web of Science and Scopus. Longitudinal and cross-sectional studies were included, the later only if a subclinical marker of disease was evaluated. The methodological quality was assessed with the Newcastle Ottawa Scale and a checklist for Analytical Cross-Sectional Studies developed in the Joanna Briggs Institute. A total of 58 articles were identified that showed high heterogenicity in the specific phthalates assessed, time-window of exposure and duration of follow-up. The quality of the studies was evaluated as high (n = 46, score >7 points) or medium (n = 12, score 4-6). The most frequently studied phthalates were DEHP-MEHP, MBzP and MEP. The evidence revealed a positive association between prenatal (in utero) exposure to most phthalates and markers of obesity in the offspring, but contradictory results when postnatal exposure and obesity were assessed. Moreover, postnatal phthalate exposure showed positive and very consistent associations with markers of diabetes and, to a lesser extent, with triglyceride levels. However, fewer evidence and contradictory results were found for HDL-c levels and markers of hypertension. The suggested mechanisms for these metabolic effects include transcription factor PPAR activation, antagonism of thyroid hormone function, antiandrogenic effects, oxidative stress and inflammation, and epigenetic changes. Nevertheless, as the inconsistency of some results could be related to differences in the study design, future research should aim to standardise the exposure assessment.
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Affiliation(s)
- Celia Perez-Diaz
- Universidad de Granada. Department of Preventive Medicine and Public Health, Pharmacy School. Campus de Cartuja S/n, 18071, Granada, Spain; Instituto de Investigación Biosanitaria (ibs.GRANADA). Avda. de Madrid, 15. Pabellón de Consultas Externas 2, 2(a) Planta, 18012, Granada, Spain
| | - Maialen Uriz-Martínez
- Universidad de Granada. Department of Preventive Medicine and Public Health, Pharmacy School. Campus de Cartuja S/n, 18071, Granada, Spain
| | - Carmen Ortega-Rico
- Universidad de Granada. Department of Preventive Medicine and Public Health, Pharmacy School. Campus de Cartuja S/n, 18071, Granada, Spain
| | - Ester Leno-Duran
- Universidad de Granada. Department of Obstetrics and Gynaecology, Medicine School. Parque Tecnologico de La Salud, Av. de La Investigación, 11, 18016, Granada, Spain.
| | - Rocío Barrios-Rodríguez
- Universidad de Granada. Department of Preventive Medicine and Public Health, Pharmacy School. Campus de Cartuja S/n, 18071, Granada, Spain; Instituto de Investigación Biosanitaria (ibs.GRANADA). Avda. de Madrid, 15. Pabellón de Consultas Externas 2, 2(a) Planta, 18012, Granada, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Instituto de Salud Carlos III, C/ Monforte de Lemos 3-5, Pabellón 11. Planta 0, 28029 Madrid, Spain
| | - Inmaculada Salcedo-Bellido
- Universidad de Granada. Department of Preventive Medicine and Public Health, Pharmacy School. Campus de Cartuja S/n, 18071, Granada, Spain; Instituto de Investigación Biosanitaria (ibs.GRANADA). Avda. de Madrid, 15. Pabellón de Consultas Externas 2, 2(a) Planta, 18012, Granada, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Instituto de Salud Carlos III, C/ Monforte de Lemos 3-5, Pabellón 11. Planta 0, 28029 Madrid, Spain
| | - Juan Pedro Arrebola
- Universidad de Granada. Department of Preventive Medicine and Public Health, Pharmacy School. Campus de Cartuja S/n, 18071, Granada, Spain; Instituto de Investigación Biosanitaria (ibs.GRANADA). Avda. de Madrid, 15. Pabellón de Consultas Externas 2, 2(a) Planta, 18012, Granada, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Instituto de Salud Carlos III, C/ Monforte de Lemos 3-5, Pabellón 11. Planta 0, 28029 Madrid, Spain
| | - Pilar Requena
- Universidad de Granada. Department of Preventive Medicine and Public Health, Pharmacy School. Campus de Cartuja S/n, 18071, Granada, Spain; Instituto de Investigación Biosanitaria (ibs.GRANADA). Avda. de Madrid, 15. Pabellón de Consultas Externas 2, 2(a) Planta, 18012, Granada, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Instituto de Salud Carlos III, C/ Monforte de Lemos 3-5, Pabellón 11. Planta 0, 28029 Madrid, Spain
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13
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Mitsuno R, Kaneko K, Nakamura T, Kojima D, Mizutani Y, Azegami T, Yamaguchi S, Yamada Y, Jinzaki M, Kinouchi K, Yoshino J, Hayashi K. Association Between Renal Sinus Fat and Cardiometabolic and Renin-Angiotensin System Parameters in Primary Aldosteronism. J Endocr Soc 2023; 8:bvad154. [PMID: 38116128 PMCID: PMC10729860 DOI: 10.1210/jendso/bvad154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Indexed: 12/21/2023] Open
Abstract
Context Renal sinus fat (RSF) accumulation is associated with cardiometabolic diseases, such as obesity, diabetes, hypertension, and chronic kidney disease. However, clinical implications of RSF in primary aldosteronism (PA) remain unclear. Objective We aimed to investigate relationships between RSF volume and key cardiometabolic and renin-angiotensin system (RAS) parameters in PA patients and clarify the differences in these relationships between unilateral and bilateral subtypes. Methods We analyzed data obtained from well-characterized PA patients that involved 45 unilateral (median age: 52 years; 42.2% men) and 92 bilateral patients (51 years; 42.4% men). Results RSF volume normalized by renal volume (RSF%) was greater in the unilateral group than in the bilateral group (P < .05). RSF% was greater in men than in women (P < .05). RSF% positively correlated with parameters related to cardiometabolic risk, including age, body mass index, visceral fat volume, creatinine, triglycerides/high-density lipoprotein cholesterol ratio, uric acid, fasting glucose, and C-reactive protein regardless of PA subtypes (all P < .05). Intriguingly, RSF% positively correlated with plasma aldosterone concentration (PAC), aldosterone-to-renin ratio, and intact parathyroid hormone (iPTH) (all P < .05) in bilateral patients but did not correlate with RAS parameters and even showed an opposite trend in unilateral patients. In subgroup analyses by sex, these distinctions became more evident in women. After adjustment for potential confounders, RSF% remained positively correlated with PAC and iPTH in bilateral patients. Conclusion Our results indicate that RSF accumulation is involved in cardiometabolic dysfunction associated with PA. However, there were distinct correlations between RSF volume and RAS parameters according to sex and PA subtypes.
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Affiliation(s)
- Ryunosuke Mitsuno
- Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Kenji Kaneko
- Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Toshifumi Nakamura
- Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Daiki Kojima
- Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Yosuke Mizutani
- Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Tatsuhiko Azegami
- Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Shintaro Yamaguchi
- Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Yoshitake Yamada
- Department of Radiology, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Masahiro Jinzaki
- Department of Radiology, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Kenichiro Kinouchi
- Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Jun Yoshino
- Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Kaori Hayashi
- Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
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Cao X, He L, Sun R, Chen S. Gender-specific associations between abdominal adipose mass and bone mineral density in the middle-aged US population. BMC Musculoskelet Disord 2023; 24:715. [PMID: 37684622 PMCID: PMC10485967 DOI: 10.1186/s12891-023-06844-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Accepted: 08/30/2023] [Indexed: 09/10/2023] Open
Abstract
OBJECTIVES The relationship between abdominal adipose tissue and osteoporosis is poorly understood. The purpose of this study was to examine the associations of abdominal adipose tissue with bone mineral density (BMD) among a nationally representative sample of US middle-aged adults. MATERIAL AND METHODS This study included 1498 participants from the National Health and Nutrition Examination Survey 2013-2014 and 2017-2018. Dual-energy x-ray absorptiometry was used to measure BMD at the lumbar spine and femoral neck, as well as to assess abdominal adipose mass by categorizing total adipose tissue (TAT) into visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Linear regression was used to assess the relationship between abdominal adipose tissue and BMD, and logistic regression and generalized additive model were used to assess the associations of abdominal adipose tissue with the development of low BMD. RESULTS In our study, men accounted for 51.3%, and the mean age and body mass index for men and women were 49.3 and 49.6 years, and 23.9 and 28.3 kg/m2, respectively. In the univariate model, we found that abdominal adipose mass was positively associated with BMD at femoral neck and spine in both genders. In the multivariate model, among men, a negative correlation was observed between TAT and SAT and BMD at the femoral neck. Additionally, higher masses of TAT, SAT, and VAT were found to significantly increase the risk of low BMD at both the femoral neck and lumbar spine. In contrast, there was no significant association between abdominal adipose mass and BMD in middle-aged women, regardless of menopausal status. CONCLUSIONS Our finding suggested that abdominal adipose tissue, regardless of its location (SAT or VAT), may have a negative impact on BMD in middle-aged men independently of body weight, but this relationship was not observed in women. Further research is needed to confirm these findings and investigate potential mechanisms underlying these associations.
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Affiliation(s)
- Xueqin Cao
- Department of Endocrinology, The Dushu Lake Hospital Affiliated to Soochow University, Chongwen Road No. 9, Suzhou, 215000, Jiangsu, China
| | - Leilei He
- Department of Obstetrics and Gynecology, The Dushu Lake Hospital Affiliated to Soochow University, Chongwen Road No. 9, Suzhou, 215000, Jiangsu, China
| | - Rong Sun
- Department of Endocrinology, The Dushu Lake Hospital Affiliated to Soochow University, Chongwen Road No. 9, Suzhou, 215000, Jiangsu, China
| | - Siyu Chen
- Department of Endocrinology, The Dushu Lake Hospital Affiliated to Soochow University, Chongwen Road No. 9, Suzhou, 215000, Jiangsu, China.
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15
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Zhou R, Chen H, Lin Y, Li F, Zhong Q, Huang Y, Wu X. Total and Regional Fat/Muscle Mass Ratio and Risks of Incident Cardiovascular Disease and Mortality. J Am Heart Assoc 2023; 12:e030101. [PMID: 37642038 PMCID: PMC10547339 DOI: 10.1161/jaha.123.030101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Accepted: 08/03/2023] [Indexed: 08/31/2023]
Abstract
Background To evaluate the sex-specific associations of total and regional fat/muscle mass ratio (FMR) with cardiovascular disease (CVD) incidence and mortality, and to explore the underlying mechanisms driven by cardiometabolites and inflammatory cells. We compared the predictive value of FMRs to body mass index. Methods and Results This population-based, prospective cohort study included 468 885 UK Biobank participants free of CVD at baseline. Fat mass and muscle mass were estimated using a bioelectrical impedance assessment device. FMR was calculated as fat mass divided by muscle mass in corresponding body parts (total body, trunk, arm, and leg). Multivariable Cox proportional hazards models and mediation analyses were used. During 12.5 years of follow-up, we documented 49 936 CVD cases and 4158 CVD deaths. Higher total FMR was associated with an increased risk of incident CVD (hazard ratios [HRs] were 1.63 and 1.83 for men and women, respectively), ischemic heart disease (men: HR, 1.61; women: HR, 1.81), myocardial infarction (men: HR, 1.72; women: HR, 1.49), and congestive heart failure (men: HR, 2.25; women: HR, 2.57). The positive associations of FMRs with mortality from total CVD or its subtypes were significant mainly in trunk and arm for male patients (P for trend <0.05). We also identified 8 cardiometabolites and 5 inflammatory cells that partially mediated FMR-CVD associations. FMRs were modestly better at discriminating cardiovascular mortality risk. Conclusions Higher total and regional FMRs were associated with an increased risk of CVD and mortality, partly mediated through cardiometabolites and inflammatory cells. Early monitoring of FMR should be considered to alleviate CVD risk. FMRs were superior to body mass index in predicting CVD mortality.
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Affiliation(s)
- Rui Zhou
- Department of Epidemiology, School of Public Health (Guangdong Provincial Key Laboratory of Tropical Disease Research)Southern Medical UniversityGuangzhouChina
| | - Hao‐Wen Chen
- Department of Epidemiology, School of Public Health (Guangdong Provincial Key Laboratory of Tropical Disease Research)Southern Medical UniversityGuangzhouChina
| | - Yang Lin
- Center for Disease Control and Prevention of Chaoyang District of BeijingBeijingChina
| | - Fu‐Rong Li
- School of MedicineSouthern University of Science and TechnologyShenzhenChina
| | - Qi Zhong
- Department of Epidemiology, School of Public Health (Guangdong Provincial Key Laboratory of Tropical Disease Research)Southern Medical UniversityGuangzhouChina
| | - Yi‐Ning Huang
- Department of Epidemiology, School of Public Health (Guangdong Provincial Key Laboratory of Tropical Disease Research)Southern Medical UniversityGuangzhouChina
| | - Xian‐Bo Wu
- Department of Epidemiology, School of Public Health (Guangdong Provincial Key Laboratory of Tropical Disease Research)Southern Medical UniversityGuangzhouChina
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Aitzetmüller-Klietz ML, Busch L, Hamatschek M, Paul M, Schriek C, Wiebringhaus P, Aitzetmüller-Klietz M, Kückelhaus M, Hirsch T. Understanding the Vicious Circle of Pain, Physical Activity, and Mental Health in Lipedema Patients-A Response Surface Analysis. J Clin Med 2023; 12:5319. [PMID: 37629361 PMCID: PMC10455654 DOI: 10.3390/jcm12165319] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 08/11/2023] [Accepted: 08/14/2023] [Indexed: 08/27/2023] Open
Abstract
Lipedema is a widespread disease with painful accumulations of subcutaneous fat in the legs and arms. Often, obesity co-occurs. Many patients suffer from impairment in mobility and mental health. Obesity and mental health in turn can be positively influenced by physical activity. In this study, we aimed to examine the interrelations between pain and physical activity on mental health in lipedema patients. In total, 511 female lipedema patients (age M = 40.16 ± 12.45 years, BMI M = 33.86 ± 7.80 kg/m2) filled in questionnaires measuring pain, physical activity, and mental health (PHQ-9; WHOQOL-BREF with subscales mental, physical, social, environmental, and overall health). Response surface analyses were calculated via R statistics. The explained variance was high for the model predicting depression severity (R2 = 0.18, p < 0.001) and physical health (R2 = 0.30, p < 0.001). Additive incongruence effects of pain and physical activity on depression severity, mental, physical, and overall health were found (all p < 0.001). In our study, physical activity and pain synergistically influenced physical, mental, and overall health. The pain not only led to low mental health but also interfered with the valuable potential of engaging in physical activity in lipedema patients.
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Affiliation(s)
- Marie-Luise Aitzetmüller-Klietz
- Department of Plastic, Reconstructive and Aesthetic Surgery, Hand Surgery, Fachklinik Hornheide, 48157 Muenster, Germany
- Plastic and Reconstructive Surgery, Institute of Musculoskeletal Medicine, Westfalian Wilhelms-University, 48149 Muenster, Germany
- Division of Plastic and Reconstructive Surgery, Department of Trauma, Hand and Reconstructive Surgery, University Hospital Muenster, 48149 Muenster, Germany
| | - Lena Busch
- Department of Plastic, Reconstructive and Aesthetic Surgery, Hand Surgery, Fachklinik Hornheide, 48157 Muenster, Germany
- Plastic and Reconstructive Surgery, Institute of Musculoskeletal Medicine, Westfalian Wilhelms-University, 48149 Muenster, Germany
- Academy for Diagnostics and Prevention, 48149 Muenster, Germany
| | - Matthias Hamatschek
- Department of Plastic, Reconstructive and Aesthetic Surgery, Hand Surgery, Fachklinik Hornheide, 48157 Muenster, Germany
- Plastic and Reconstructive Surgery, Institute of Musculoskeletal Medicine, Westfalian Wilhelms-University, 48149 Muenster, Germany
| | - Matthias Paul
- Academy for Diagnostics and Prevention, 48149 Muenster, Germany
- Department of Cardiovascular Medicine, Division Steinfurt, University Hospital Muenster, 48565 Steinfurt, Germany
| | - Carsten Schriek
- Academy for Diagnostics and Prevention, 48149 Muenster, Germany
| | - Philipp Wiebringhaus
- Department of Plastic, Reconstructive and Aesthetic Surgery, Hand Surgery, Fachklinik Hornheide, 48157 Muenster, Germany
- Plastic and Reconstructive Surgery, Institute of Musculoskeletal Medicine, Westfalian Wilhelms-University, 48149 Muenster, Germany
- Division of Plastic and Reconstructive Surgery, Department of Trauma, Hand and Reconstructive Surgery, University Hospital Muenster, 48149 Muenster, Germany
| | - Matthias Aitzetmüller-Klietz
- Department of Plastic, Reconstructive and Aesthetic Surgery, Hand Surgery, Fachklinik Hornheide, 48157 Muenster, Germany
- Plastic and Reconstructive Surgery, Institute of Musculoskeletal Medicine, Westfalian Wilhelms-University, 48149 Muenster, Germany
- Division of Plastic and Reconstructive Surgery, Department of Trauma, Hand and Reconstructive Surgery, University Hospital Muenster, 48149 Muenster, Germany
| | - Maximilian Kückelhaus
- Department of Plastic, Reconstructive and Aesthetic Surgery, Hand Surgery, Fachklinik Hornheide, 48157 Muenster, Germany
- Plastic and Reconstructive Surgery, Institute of Musculoskeletal Medicine, Westfalian Wilhelms-University, 48149 Muenster, Germany
- Division of Plastic and Reconstructive Surgery, Department of Trauma, Hand and Reconstructive Surgery, University Hospital Muenster, 48149 Muenster, Germany
| | - Tobias Hirsch
- Department of Plastic, Reconstructive and Aesthetic Surgery, Hand Surgery, Fachklinik Hornheide, 48157 Muenster, Germany
- Plastic and Reconstructive Surgery, Institute of Musculoskeletal Medicine, Westfalian Wilhelms-University, 48149 Muenster, Germany
- Division of Plastic and Reconstructive Surgery, Department of Trauma, Hand and Reconstructive Surgery, University Hospital Muenster, 48149 Muenster, Germany
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17
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Ma W, Zhu H, Yu X, Zhai X, Li S, Huang N, Liu K, Shirai K, Sheerah HA, Cao J. Association between android fat mass, gynoid fat mass and cardiovascular and all-cause mortality in adults: NHANES 2003-2007. Front Cardiovasc Med 2023; 10:1055223. [PMID: 37273879 PMCID: PMC10233278 DOI: 10.3389/fcvm.2023.1055223] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Accepted: 04/14/2023] [Indexed: 06/06/2023] Open
Abstract
Objectives Evidence of the relationship between android fat mass and gynoid fat mass with the mortality prediction is still limited. Current study analyzed the NHANES database to investigate the relationship between android fat mass, gynoid fat mass and CVD, with all-cause mortality. Method The study subjects were NHANES participants over 20 years old, two indicators of regional body composition, android fat and gynoid fat were measured by Dual Energy x-ray Absorptiometry (DEXA). The other various covariates data obtained from the NHANES questionnaire and laboratory measurements, including age, gender, education, race/ethnicity, uric acid, total serum cholesterol, albumin, Vitamin C, folate, alcohol drinking, smoking status, history of diabetes, and hypertension. Mortality status was ascertained from a linked mortality file prepared by the National Center for Health Statistics. The study population was divided quartiles based on the distribution of android fat mass and gynoid fat mass. The relationship between these two indicators with cardiovascular and all-cause mortality was investigated by using Cox regression. The covariates age, gender, smoking status, drinking status, history of diabetes, and history of hypertension were stratified. Results In the fully adjusted model, Q3 had the lowest HR in android fat mass and gynoid fat mass. When examining the relationship between android fat mass and CVD mortality, current smokers and drinkers had the lowest CVD risk in Q2 [smoking: 0.21 (0.08, 0.52), drinking: 0.14 (0.04, 0.50)]. In diabetic patients, compared with Q1, other groups with increased android fat mass can significantly reduce the risk of CVD [Q4: 0.17 (0.04, 0.75), Q3: 0.18 (0.03, 1.09), Q2: 0.27 (0.09, 0.83)]. In ≥60 years old and female, the greater the gynoid fat mass, the smaller the HR of all-cause mortality [Q4 for ≥60 years old: 0.57 (0.33, 0.96), Q4 for female: 0.37 (0.23, 0.58)]. People <60 years old had a lower risk of all-cause mortality with gynoid fat mass in Q3 than those ≥60 years old [<60 years: 0.50 (0.27, 0.91), ≥60 years: 0.65 (0.45, 0.95)]. Among subjects without hypertension, the group with the largest android fat mass had the lowest risk of CVD mortality, and the group with the largest gynoid fat mass had the lowest risk of all-cause mortality [Android fat mass: 0.36 (0.16, 0.81), gynoid fat mass: 0.57 (0.39, 0.85)]. Conclusion Moderate android fat mass and gynoid fat mass (Q3) had the most protective effect. Smokers and drinkers need to control their body fat. Being too thin is harmful to people with diabetes. Increased gynoid fat mass is a protective factor for all-cause mortality in older adults and females. Young people's gynoid fat mass is more protective in the moderate range than older people's. If no high blood pressure exists, people with more android and gynoid fat mass have a lower risk of CVD or all-cause mortality.
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Affiliation(s)
- Wenzhi Ma
- School of Public Health, Wuhan University, Wuhan, China
| | - Huiping Zhu
- School of Public Health, Capital Medical University, Beijing, China
| | - Xinyi Yu
- School of Public Health, Capital Medical University, Beijing, China
| | - Xiaobing Zhai
- Center for Artificial Intelligence Driven Drug Discovery, Faculty of Applied Sciences, Macao Polytechnic University, Macao, China
| | - Shiyang Li
- School of Public Health, Wuhan University, Wuhan, China
| | - Nian Huang
- School of Public Health, Wuhan University, Wuhan, China
| | - Keyang Liu
- Public Health, Department of Social Medicine, Osaka University Graduate School of Medicine, Suita-shi, Japan
| | - Kokoro Shirai
- Public Health, Department of Social Medicine, Osaka University Graduate School of Medicine, Suita-shi, Japan
| | - Haytham A. Sheerah
- Assistant Deputyship for International Collaborations, Ministry of Health, Riyadh, Saudi Arabia
| | - Jinhong Cao
- School of Management, Hubei University of Chinese Medicine, Wuhan, China
- Research Center for the Development of Chinese Medicine, Hubei Province Project of Key Research Institute of Humanities and Social Sciences at Universities, Wuhan, China
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Yang L, Huang H, Liu Z, Ruan J, Xu C. Association of the android to gynoid fat ratio with nonalcoholic fatty liver disease: a cross-sectional study. Front Nutr 2023; 10:1162079. [PMID: 37255941 PMCID: PMC10226647 DOI: 10.3389/fnut.2023.1162079] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Accepted: 04/27/2023] [Indexed: 06/01/2023] Open
Abstract
Background Nonalcoholic fatty liver disease (NAFLD) is becoming a severe global public health problem, and can developed into fibrotic nonalcoholic steatohepatitis (NASH), but its risk factors have not been fully identified. The objective of this study was to investigate the association between the android-to-gynoid fat ratio (A/G ratio) and the prevalence of NAFLD. Methods This cross-sectional study is based on the 2003-2006 and 2011-2018 cycles of the National Health and Nutrition Examination Survey and included 10,989 participants. Participants aged 20 and older without viral hepatitis or significant alcohol consumption were included. Dual-energy X-ray absorptiometry was used to assess body composition. NAFLD was diagnosed using the United States fatty liver index (US FLI). Multivariable logistic regression models were used to evaluate the association between the A/G ratio and NAFLD. Results The prevalence of NAFLD was 32.15% among the study population. Android percent fat and the A/G ratio were significantly higher in patients with NAFLD than in those without NAFLD [41.68% (0.25) vs. 32.80% (0.27), p < 0.001; 1.14 ± 0.01 vs. 0.94 ± 0.00, p < 0.001, respectively]. Logistic regression analysis showed that android percent fat was positively correlated to NAFLD (OR: 1.15, 95% CI: 1.11-1.18), while gynoid percent fat was negatively correlated to NAFLD (OR: 0.92, 95% CI: 0.90-0.94), and the A/G ratio was significantly associated with the prevalence of NAFLD (OR: 1.59, 95% CI: 1.38-1.82) and fibrotic NASH (OR: 2.01, 95% CI: 1.71-2.38). We also found that females had a notably diminished A/G ratio compared with males (0.91 vs. 1.12, p < 0.001). In addition, the female population proportion was negatively correlated with the A/G ratio, which may partly explain the lower prevalence of NAFLD in females. What is more, the OR value of the A/G ratio in the female subgroup was much higher than that in the male subgroup in all adjusted models. Conclusion A/G ratio is significantly associated with NAFLD and fibrotic NASH. Women have a lower A/G ratio than men, which may explain the sex difference in NAFLD prevalence. Furthermore, with a higher A/G ratio, the association between females and NAFLD are greatly elevated.
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Affiliation(s)
- Ling Yang
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Hangkai Huang
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Zhening Liu
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jiaqi Ruan
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Chengfu Xu
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang Provincial Clinical Research Center for Digestive Diseases, Hangzhou, China
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Lu Y, Qin L, Wei Y, Mo X, Tang X, Liu Q, Liu S, Zhang J, Xu M, Wei C, Huang S, Lin Y, Luo T, Mai T, Gou R, Zhang Z, Cai J, Qin J. Association between barium exposed, CYP19A1 and central obesity: A cross-sectional study in rural China. J Trace Elem Med Biol 2023; 78:127170. [PMID: 37075568 DOI: 10.1016/j.jtemb.2023.127170] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Revised: 03/04/2023] [Accepted: 04/03/2023] [Indexed: 04/21/2023]
Abstract
BACKGROUND obesity is a major risk factor for many metabolic diseases such as diabetes and cardiometabolic diseases. This study aimed to evaluate the association of plasma and urinary barium concentrations, CYP19A1 gene polymorphisms, and their interaction with central obesity in a rural Chinese population. METHODS restricted cubic spline model was used to explore the dose-response relationship between barium and the risk of developing central obesity and waist circumference; logistic regression model was used to assess the association between barium, CYP19A1 gene polymorphisms and their interaction with central obesity. RESULTS the results of the restricted cubic spline model showed that plasma barium concentration was linearly associated with the risk of developing central obesity and non-linearly associated with waist circumference. Logistic regression analysis showed that participants with Q4 plasma barium concentration exhibited a higher risk of central obesity compared to participants with Q1 barium concentration; participants carrying the rs10046-AA gene exhibited a lower risk of central obesity than those carrying the rs10046-G(GG+GA) gene; participants carrying the rs10046-GA genotype showed 1.754 times higher risk of central obesity than those carrying rs10046-GG+AA genotype. There was a significant interaction between plasma barium and CYP19A1 gene polymorphism on central obesity. CONCLUSION the development of central obesity was associated with plasma barium and CYP19A1.
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Affiliation(s)
- Yufu Lu
- School of Public Health, Guangxi Medical University, Shuangyong Road No.22, Nanning 530021, Guangxi, China
| | - Lidong Qin
- School of Public Health, Guangxi Medical University, Shuangyong Road No.22, Nanning 530021, Guangxi, China
| | - Yanfei Wei
- School of Public Health, Guangxi Medical University, Shuangyong Road No.22, Nanning 530021, Guangxi, China
| | - Xiaoting Mo
- School of Public Health, Guangxi Medical University, Shuangyong Road No.22, Nanning 530021, Guangxi, China
| | - Xu Tang
- School of Public Health, Guangxi Medical University, Shuangyong Road No.22, Nanning 530021, Guangxi, China
| | - Qiumei Liu
- School of Public Health, Guangxi Medical University, Shuangyong Road No.22, Nanning 530021, Guangxi, China
| | - Shuzhen Liu
- School of Public Health, Guangxi Medical University, Shuangyong Road No.22, Nanning 530021, Guangxi, China
| | - Junling Zhang
- School of Public Health, Guangxi Medical University, Shuangyong Road No.22, Nanning 530021, Guangxi, China
| | - Min Xu
- School of Public Health, Guangxi Medical University, Shuangyong Road No.22, Nanning 530021, Guangxi, China
| | - Chunmei Wei
- School of Public Health, Guangxi Medical University, Shuangyong Road No.22, Nanning 530021, Guangxi, China
| | - Shenxiang Huang
- School of Public Health, Guangxi Medical University, Shuangyong Road No.22, Nanning 530021, Guangxi, China
| | - Yinxia Lin
- School of Public Health, Guangxi Medical University, Shuangyong Road No.22, Nanning 530021, Guangxi, China
| | - Tingyu Luo
- School of Public Health, Guilin Medical University, 20 Lequn Road, Guilin, Guangxi, China
| | - Tingyu Mai
- School of Public Health, Guilin Medical University, 20 Lequn Road, Guilin, Guangxi, China
| | - Ruoyu Gou
- School of Public Health, Guilin Medical University, 20 Lequn Road, Guilin, Guangxi, China
| | - Zhiyong Zhang
- School of Public Health, Guilin Medical University, 20 Lequn Road, Guilin, Guangxi, China; Guangxi key laboratory of Environmental Exposomics and Entire Lifecycle Health, China
| | - Jiansheng Cai
- School of Public Health, Guilin Medical University, 20 Lequn Road, Guilin, Guangxi, China; Guangxi Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin, Guangxi, China.
| | - Jian Qin
- Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education, Guangxi Medical University, Nanning 530021, China; Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, School of Public Health, Guangxi Medical University, Nanning 530021, China; Guangxi Key Laboratory of Environment and Health Research, Guangxi Medical University, Nanning 530021, China.
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Xing W, Gu W, Liang M, Wang Z, Fan D, Zhang B, Wang L. Association between aldehyde exposure and sex steroid hormones among adults. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2023; 30:30444-30461. [PMID: 36434445 DOI: 10.1007/s11356-022-24362-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Accepted: 11/17/2022] [Indexed: 06/16/2023]
Abstract
Exogenous and endogenous exposure to aldehydes is seen worldwide. Aldehydes are closely associated with human diseases, especially reproductive toxicity. However, the effect of aldehyde exposure on sex steroid hormones among adults remains uninvestigated. A total of 851 participants aged over 18 years were included in this cross-sectional analysis based on data from National Health and Nutrition Examination Survey (NHANES) 2013-2014. Serum aldehyde concentrations were quantified following an automated analytical method. Sex steroid hormones including total testosterone, estradiol, and sex hormone binding globulin (SHBG) were detected. Multivariate linear regression models, forest plots, generalized additive model (GAM), and smooth curve fitting analysis were used to assess the associations between quartiles of aldehydes and sex steroid hormones levels after adjusting for potential confounders. Butyraldehyde and propanaldehyde were found to be negatively associated with estradiol and SHBG in females and males, respectively. β values with 95% confidence intervals (95% CIs) were - 20.59 (- 38.30 to - 2.88) for Q2 vs. Q1 of butyraldehyde and - 8.13 (- 14.92 to - 1.33) and - 7.79 (- 14.91 to - 0.67) for Q2 vs. Q1 and Q4 vs. Q1 of propanaldehyde. No significant associations were observed between other aldehydes and sex hormones. In premenopausal women, isopentanaldehyde was inversely associated with serum total testosterone levels (Q4 vs. Q1: OR = - 7.95, 95% CI: - 15.62 to - 0.27), whereas propanaldehyde was positively associated with serum estradiol concentration (Q3 vs. Q1: β = 28.88, 95% CI: 0.83 to 56.94). Compared with Q1, Q3 of isopentanaldehyde was associated with 3.53 pg/mL higher concentration of estradiol in postmenopausal women (β = 3.53, 95% CI: 0.08 to 6.97). Moreover, in males under 40 years, butyraldehyde and heptanaldehyde were inversely proportional to total testosterone levels and heptanaldehyde and butyraldehyde were negatively associated with estradiol and SHBG. Decreased total testosterone, elevated estradiol, and decreased SHBG levels were found in higher quartiles of benzaldehyde, hexanaldehyde and isopentanaldehyde, and propanaldehyde, respectively, in males aged over 60 years. In male participants aged 40-60 years, only hexanaldehyde was observed to be correlated with higher serum estradiol levels. In conclusion, our current research presented the association between six serum aldehydes and sex hormones. Of note, stratification analyses were conducted in participants with different menopausal statuses and age among males and females. Sex- and age-specific effect of aldehyde exposure on alterations in sex hormone levels were observed. Further studies are warranted to confirm the causal relationship and explore the underlying mechanisms.
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Affiliation(s)
- Weilong Xing
- Laboratory of Pesticide Environmental Assessment and Pollution Control, Nanjing Institute of Environmental Sciences, Ministry of Ecology and Environment (MEE), Nanjing, 210042, People's Republic of China.
| | - Wen Gu
- Laboratory of Pesticide Environmental Assessment and Pollution Control, Nanjing Institute of Environmental Sciences, Ministry of Ecology and Environment (MEE), Nanjing, 210042, People's Republic of China
| | - Mengyuan Liang
- Laboratory of Pesticide Environmental Assessment and Pollution Control, Nanjing Institute of Environmental Sciences, Ministry of Ecology and Environment (MEE), Nanjing, 210042, People's Republic of China
| | - Zhen Wang
- Laboratory of Pesticide Environmental Assessment and Pollution Control, Nanjing Institute of Environmental Sciences, Ministry of Ecology and Environment (MEE), Nanjing, 210042, People's Republic of China
| | - Deling Fan
- Laboratory of Pesticide Environmental Assessment and Pollution Control, Nanjing Institute of Environmental Sciences, Ministry of Ecology and Environment (MEE), Nanjing, 210042, People's Republic of China
| | - Bing Zhang
- Laboratory of Pesticide Environmental Assessment and Pollution Control, Nanjing Institute of Environmental Sciences, Ministry of Ecology and Environment (MEE), Nanjing, 210042, People's Republic of China
| | - Lei Wang
- Laboratory of Pesticide Environmental Assessment and Pollution Control, Nanjing Institute of Environmental Sciences, Ministry of Ecology and Environment (MEE), Nanjing, 210042, People's Republic of China
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Li S, Zhang W, Fu Z, Liu H. Impact of obesity on all-cause and cause-specific mortality among critically ill men and women: a cohort study on the eICU database. Front Nutr 2023; 10:1143404. [PMID: 37153915 PMCID: PMC10160369 DOI: 10.3389/fnut.2023.1143404] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Accepted: 04/03/2023] [Indexed: 05/10/2023] Open
Abstract
Background The effect of obesity on intensive care unit outcomes among critically ill patients and whether there are sex differences have not been well investigated. We sought to determine the association between obesity and 30-day all-cause and cause-specific mortality among critically ill men and women. Methods Adult participants who had body mass index (BMI) measurements were included from the eICU database. Participants were divided into six groups according to BMI (kg/m2) categories (underweight, <18.5; normal weight, 18.5-24.9; overweight, 25-29.9; class I obesity, 30-34.9; class II obesity, 35-39.9; class III obesity, ≥40). A multivariable adjusted logistic model was conducted with odds ratios (ORs) and 95% confidence intervals (CIs). A cubic spline curve based on the generalized additive model was used to represent the nonlinear association. Stratified analysis and sensitivity analysis were also performed. Results A total of 160,940 individuals were included in the analysis. Compared with the class I obesity category, the underweight and normal weight categories had higher all-cause mortality, and the multivariable adjusted ORs were 1.62 (95% CI: 1.48-1.77) and 1.20 (95% CI: 1.13-1.27) for the general population, 1.76 (95% CI: 1.54-2.01) and 1.22 (95% CI: 1.13-1.32) for men, and 1.51 (95% CI: 1.33-1.71) and 1.16 (95% CI: 1.06-1.27) for women, respectively. Accordingly, multivariable adjusted ORs for the class III obesity category were 1.14 (95% CI: 1.05-1.24) for the general population, 1.18 (95% CI: 1.05-1.33) for men, and 1.10 (95% CI: 0.98-1.23) for women. With cubic spline curves, the association between BMI and all-cause mortality was U-shaped or reverse J-shaped. Similar findings were observed for cause-specific mortality, with the underweight category associated with a higher risk of mortality. Class III obesity increased the risk of cardiovascular death among men (OR 1.51; 95% CI: 1.23-1.84) and increased the risk of other-cause death among women (OR 1.33; 95% CI: 1.10-1.61). Conclusion The obesity paradox appears to be suitable for all-cause and cause-specific mortality among critically ill men and women. However, the protective effect of obesity cannot be extended to severely obese individuals. The association between BMI and cardiovascular mortality was sex-specific and was more pronounced among men than among women. Graphical abstract.
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Affiliation(s)
- Shan Li
- Department of Cardiology, The Second Medical Center, Chinese People’s Liberation Army General Hospital, Beijing, China
- National Clinical Research Center for Geriatric Disease, Beijing, China
- *Correspondence: Shan Li,
| | - Wei Zhang
- National Clinical Research Center for Geriatric Disease, Beijing, China
- Department of Outpatient, The Second Medical Center, Chinese People’s Liberation Army General Hospital, Beijing, China
| | - Zhiqing Fu
- Department of Cardiology, The Second Medical Center, Chinese People’s Liberation Army General Hospital, Beijing, China
- National Clinical Research Center for Geriatric Disease, Beijing, China
| | - Hongbin Liu
- Department of Cardiology, The Second Medical Center, Chinese People’s Liberation Army General Hospital, Beijing, China
- National Clinical Research Center for Geriatric Disease, Beijing, China
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22
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Zhao H, Zong Y, Li W, Wang Y, Zhao W, Meng X, Yang F, Kong J, Zhao X, Wang J. Damp-heat constitution influences gut microbiota and urine metabolism of Chinese infants. Heliyon 2022; 9:e12424. [PMID: 36755610 PMCID: PMC9900481 DOI: 10.1016/j.heliyon.2022.e12424] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 11/15/2022] [Accepted: 12/09/2022] [Indexed: 12/25/2022] Open
Abstract
Background As an increasingly popular complementary and alternative approach for early detection and treatment of disease, traditional Chinese medicine constitution (TCMC) divides human beings into those with balanced constitution (BC) and unbalanced constitution, where damp-heat constitution (DHC) is one of the most unbalanced constitutions. Many studies have been carried out on the microscopic mechanism of constitution classification; however, most of these studies were conducted in adults and rarely in infants. Many diseases are closely related to intestinal microbiota, and metabolites produced by the interaction between microbiota and the body may impact constitution classification. Herein, we investigated the overall constitution distribution in Chinese infants, and analyzed the profiles of gut microbiota and urine metabolites of DHC to further promote the understanding of infants constitution classification. Methods General information was collected and TCMC was evaluated by Constitutional Medicine Questionnaires. 1315 questionnaires were received in a cross-sectional study to investigate the constitution composition in Chinese infants. A total of 56 infants, including 30 DHC and 26 BC, were randomly selected to analyze gut microbiota by 16S rRNA sequencing and urine metabolites by UPLC-Q-TOF/MS method. Results BC was the most common constitution in Chinese infants, DHC was the second common constitution. The gut microbiota and urine metabolites in the DHC group showed different composition compared to the BC group. Four differential genera and twenty differential metabolites were identified. In addition, the combined marker composed of four metabolites may have the high potential to discriminate DHC from BC with an AUC of 0.765. Conclusions The study revealed the systematic differences in the gut microbiota and urine metabolites between infants with DHC and BC. Moreover, the differential microbiota and metabolites may offer objective evidences for constitution classification.
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Affiliation(s)
- Haihong Zhao
- National Institute of Traditional Chinese Medicine Constitution and Preventive Treatment of Disease, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Yuhan Zong
- National Institute of Traditional Chinese Medicine Constitution and Preventive Treatment of Disease, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Wenle Li
- National Institute of Traditional Chinese Medicine Constitution and Preventive Treatment of Disease, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Yaqi Wang
- College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, China
| | - Weibo Zhao
- National Institute of Traditional Chinese Medicine Constitution and Preventive Treatment of Disease, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Xianghe Meng
- Neurology Department, Xuanwu Hospital of Capital Medical University, Beijing, 100053, China
| | - Fan Yang
- National Institute of Traditional Chinese Medicine Constitution and Preventive Treatment of Disease, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Jingwei Kong
- Nutrition and Metabolism Research Division, Innovation Center, Heilongjiang Feihe Dairy Co., Ltd., Beijing, 100015, China
| | - Xiaoshan Zhao
- National Institute of Traditional Chinese Medicine Constitution and Preventive Treatment of Disease, Beijing University of Chinese Medicine, Beijing, 100029, China,School of Chinese Medicine, Southern Medical University, Guangzhou, 510515, Guangdong, China
| | - Ji Wang
- National Institute of Traditional Chinese Medicine Constitution and Preventive Treatment of Disease, Beijing University of Chinese Medicine, Beijing, 100029, China,Corresponding author.
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23
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The corrugator supercilii for craniofacial reconstruction: a systematic review. EUROPEAN JOURNAL OF PLASTIC SURGERY 2022. [DOI: 10.1007/s00238-022-02023-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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Li Y, Gao D, Liu J, Yang Z, Wen B, Chen L, Chen M, Ma Y, Ma T, Dong B, Song Y, Huang S, Dong Y, Ma J. Prepubertal BMI, pubertal growth patterns, and long-term BMI: Results from a longitudinal analysis in Chinese children and adolescents from 2005 to 2016. Eur J Clin Nutr 2022; 76:1432-1439. [PMID: 35523866 DOI: 10.1038/s41430-022-01133-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Revised: 03/20/2022] [Accepted: 03/24/2022] [Indexed: 11/08/2022]
Abstract
OBJECTIVE To assess the effects of prepubertal BMI on pubertal growth patterns, and the influence of prepubertal BMI and pubertal growth patterns on long-term BMI among Chinese children and adolescents. METHODS A total of 9606 individuals aged between 7 and 18 years from longitudinal surveys in Zhongshan city of China from 2005 to 2016 were enrolled. Age at peak height velocity (APHV) and peak height velocity (PHV) were estimated using Super-Imposition by Translation and Rotation (SITAR) model. Associations between prepubertal BMI, APHV, PHV, and long-term overweight and obesity were assessed by linear regression and multinominal logistic regression. Scatter plots were elaborated to show the associations between prepubertal BMI and pubertal growth patterns according to prepubertal BMI categories. RESULTS Prepubertal BMI Z-Score was positively correlated with long-term BMI Z-Score, and negatively correlated with APHV in both sexes. In addition, there was a negative association between prepubertal BMI Z-Score and PHV in boys. With 1-year decrease in APHV, risk of long-term underweight decreased by 92%, while overweight increased by 33% in boys. Corresponding risk of long-term underweight and overweight for girls decreased by 42% and increased by 20%, respectively. CONCLUSION High prepubertal BMI levels were associated with earlier APHV and lower PHV, and the early onset of pubertal development could increase the risks of long-term overweight and obesity at 17-18 years of age both in boys and girls. Such evidence emphasized the importance of reducing prepubertal obesity risks combined with appropriate pubertal development timing, including later APHV and higher PHV, so as to prevent the obesity and related cardiovascular diseases in adulthood.
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Affiliation(s)
- Yanhui Li
- Institute of Child and Adolescent Health, School of Public Health, Peking University, 100191, Beijing, China
- National Health Commission Key Laboratory of Reproductive Health, 100191, Beijing, China
| | - Di Gao
- Institute of Child and Adolescent Health, School of Public Health, Peking University, 100191, Beijing, China
- National Health Commission Key Laboratory of Reproductive Health, 100191, Beijing, China
| | - Jieyu Liu
- Institute of Child and Adolescent Health, School of Public Health, Peking University, 100191, Beijing, China
- National Health Commission Key Laboratory of Reproductive Health, 100191, Beijing, China
| | - Zhaogeng Yang
- Institute of Child and Adolescent Health, School of Public Health, Peking University, 100191, Beijing, China
- National Health Commission Key Laboratory of Reproductive Health, 100191, Beijing, China
| | - Bo Wen
- Institute of Child and Adolescent Health, School of Public Health, Peking University, 100191, Beijing, China
- National Health Commission Key Laboratory of Reproductive Health, 100191, Beijing, China
| | - Li Chen
- Institute of Child and Adolescent Health, School of Public Health, Peking University, 100191, Beijing, China
- National Health Commission Key Laboratory of Reproductive Health, 100191, Beijing, China
| | - Manman Chen
- Institute of Child and Adolescent Health, School of Public Health, Peking University, 100191, Beijing, China
- National Health Commission Key Laboratory of Reproductive Health, 100191, Beijing, China
| | - Ying Ma
- Institute of Child and Adolescent Health, School of Public Health, Peking University, 100191, Beijing, China
- National Health Commission Key Laboratory of Reproductive Health, 100191, Beijing, China
| | - Tao Ma
- Institute of Child and Adolescent Health, School of Public Health, Peking University, 100191, Beijing, China
- National Health Commission Key Laboratory of Reproductive Health, 100191, Beijing, China
| | - Bin Dong
- Institute of Child and Adolescent Health, School of Public Health, Peking University, 100191, Beijing, China
- National Health Commission Key Laboratory of Reproductive Health, 100191, Beijing, China
| | - Yi Song
- Institute of Child and Adolescent Health, School of Public Health, Peking University, 100191, Beijing, China
- National Health Commission Key Laboratory of Reproductive Health, 100191, Beijing, China
| | - Sizhe Huang
- Zhongshan Health Care Centers for Primary and Secondary School, 528403, Zhongshan, China
| | - Yanhui Dong
- Institute of Child and Adolescent Health, School of Public Health, Peking University, 100191, Beijing, China.
- National Health Commission Key Laboratory of Reproductive Health, 100191, Beijing, China.
| | - Jun Ma
- Institute of Child and Adolescent Health, School of Public Health, Peking University, 100191, Beijing, China.
- National Health Commission Key Laboratory of Reproductive Health, 100191, Beijing, China.
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Cao W, Xu Y, Shen Y, Wang Y, Ma X, Bao Y. Associations between sex hormones and metabolic-associated fatty liver disease in a middle-aged and elderly community. Endocr J 2022; 69:1007-1014. [PMID: 35321990 DOI: 10.1507/endocrj.ej21-0559] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Metabolic-associated fatty liver disease (MAFLD) was proposed by an international expert consensus to replace non-alcoholic fatty liver disease (NAFLD) in 2020. Previous studies have shown that sex hormones are strongly linked to NAFLD development. This study aims to explore whether sex hormones are associated with MAFLD and liver fat content (LFC) in a middle-aged and elderly community. The study included 732 subjects aged 50-80 years enrolled from communities. MAFLD was diagnosed using the 2020 International Expert Consensus. LFC was calculated using parameters from abdominal ultrasound images. Serum estradiol (E2), total testosterone (TT), sex hormone-binding globulin (SHBG), FSH, and LH were measured by chemiluminescent microparticle immunoassay. MAFLD was diagnosed in 107/304 (35.2%) men and 154/428 (35.2%) women. After adjustments for confounding factors, logistic regression analysis showed that SHBG was negatively correlated with MAFLD in men (OR, 0.95 [0.93-0.97], p < 0.001). In women, SHBG and FSH were negatively correlated with MAFLD (OR, 0.95 [0.94-0.97], p < 0.001; OR, 0.97 [0.96-0.98], p < 0.001). Multivariate linear regression analysis showed that SHBG was a negative factor for LFC in both men (standardized β = -0.188, p < 0.001) and women (standardized β = -0.184, p < 0.001). FSH was a negative factor for LFC in women (standardized β = -0.082, p = 0.046). SHBG was negatively correlated with MAFLD in middle-aged and elderly men and women. Moreover, FSH was negatively correlated, and bioactive testosterone was positively correlated with MAFLD in women. These findings suggest a relationship between sex hormones and MAFLD.
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Affiliation(s)
- Weijie Cao
- Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Key Clinical Center for Metabolic Disease, 600 Yishan road, Shanghai 200233, China
| | - Yiting Xu
- Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Key Clinical Center for Metabolic Disease, 600 Yishan road, Shanghai 200233, China
| | - Yun Shen
- Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Key Clinical Center for Metabolic Disease, 600 Yishan road, Shanghai 200233, China
| | - Yufei Wang
- Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Key Clinical Center for Metabolic Disease, 600 Yishan road, Shanghai 200233, China
| | - Xiaojing Ma
- Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Key Clinical Center for Metabolic Disease, 600 Yishan road, Shanghai 200233, China
| | - Yuqian Bao
- Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Key Clinical Center for Metabolic Disease, 600 Yishan road, Shanghai 200233, China
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de Toledo VHC, Feltrin AS, Barbosa AR, Tahira AC, Brentani H. Sex differences in gene regulatory networks during mid-gestational brain development. Front Hum Neurosci 2022; 16:955607. [PMID: 36061507 PMCID: PMC9428411 DOI: 10.3389/fnhum.2022.955607] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2022] [Accepted: 07/19/2022] [Indexed: 11/13/2022] Open
Abstract
Neurodevelopmental disorders differ considerably between males and females, and fetal brain development is one of the most critical periods to determine risk for these disorders. Transcriptomic studies comparing male and female fetal brain have demonstrated that the highest difference in gene expression occurs in sex chromosomes, but several autossomal genes also demonstrate a slight difference that has not been yet explored. In order to investigate biological pathways underlying fetal brain sex differences, we applied medicine network principles using integrative methods such as co-expression networks (CEMiTool) and regulatory networks (netZoo). The pattern of gene expression from genes in the same pathway tend to reflect biologically relevant phenomena. In this study, network analysis of fetal brain expression reveals regulatory differences between males and females. Integrating two different bioinformatics tools, our results suggest that biological processes such as cell cycle, cell differentiation, energy metabolism and extracellular matrix organization are consistently sex-biased. MSET analysis demonstrates that these differences are relevant to neurodevelopmental disorders, including autism.
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Affiliation(s)
- Victor Hugo Calegari de Toledo
- Departamento e Instituto de Psiquiatria, Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo, Brazil
- Laboratório de Psicopatologia e Terapêutica Psiquiátrica (LIM23), Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo, Brazil
| | | | | | - Ana Carolina Tahira
- Laboratório de Expressão Gênica, Departamento de Parasitologia, Instituto Butantan, São Paulo, Brazil
| | - Helena Brentani
- Departamento e Instituto de Psiquiatria, Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo, Brazil
- Laboratório de Psicopatologia e Terapêutica Psiquiátrica (LIM23), Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo, Brazil
- *Correspondence: Helena Brentani
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Northey JJ, Weaver VM. Mechanosensitive Steroid Hormone Signaling and Cell Fate. Endocrinology 2022; 163:bqac085. [PMID: 35678467 PMCID: PMC9237634 DOI: 10.1210/endocr/bqac085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Indexed: 11/19/2022]
Abstract
Mechanical forces collaborate across length scales to coordinate cell fate during development and the dynamic homeostasis of adult tissues. Similarly, steroid hormones interact with their nuclear and nonnuclear receptors to regulate diverse physiological processes necessary for the appropriate development and function of complex multicellular tissues. Aberrant steroid hormone action is associated with tumors originating in hormone-sensitive tissues and its disruption forms the basis of several therapeutic interventions. Prolonged perturbations to mechanical forces may further foster tumor initiation and the evolution of aggressive metastatic disease. Recent evidence suggests that steroid hormone and mechanical signaling intersect to direct cell fate during development and tumor progression. Potential mechanosensitive steroid hormone signaling pathways along with their molecular effectors will be discussed in this context.
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Affiliation(s)
- Jason J Northey
- Department of Surgery, University of California, San Francisco, CA 94143, USA
- Center for Bioengineering and Tissue Regeneration, University of California, San Francisco, San Francisco, CA 94143,USA
| | - Valerie M Weaver
- Department of Surgery, University of California, San Francisco, CA 94143, USA
- Center for Bioengineering and Tissue Regeneration, University of California, San Francisco, San Francisco, CA 94143,USA
- UCSF Helen Diller Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143,USA
- Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94143,USA
- Department of Radiation Oncology, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143,USA
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Godbole AM, Moonie S, Coughenour C, Zhang C, Chen A, Vuong AM. Exploratory analysis of the associations between neonicotinoids and measures of adiposity among US adults: NHANES 2015-2016. CHEMOSPHERE 2022; 300:134450. [PMID: 35367485 PMCID: PMC9167792 DOI: 10.1016/j.chemosphere.2022.134450] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Revised: 03/22/2022] [Accepted: 03/25/2022] [Indexed: 05/31/2023]
Abstract
BACKGROUND Toxicology studies suggest that neonicotinoids may be associated with adiposity development via thyroid hormone disruption and increased oxidative stress. Prior epidemiological studies report mixed results for the association between neonicotinoids and adiposity measures. OBJECTIVE To examine the association between detectable concentrations of parent neonicotinoids (imidacloprid, acetamiprid, clothianidin) and neonicotinoid metabolites (5-hydroxy-imidacloprid, N-desmethyl-acetamiprid) with adiposity measures among US adults, and whether sex modifies the associations for neonicotinoid metabolites with adiposity. METHODS National Health and Nutrition Examination Survey (NHANES) 2015-2016 data was utilized to estimate covariate-adjusted associations between detectable neonicotinoids and fat mass index (FMI), lean mass index (LMI), waist circumference, body fat percentage, and body mass index (BMI) using multiple linear regression. We estimated incidence rate ratios (IRRs) for overweight or obese status with detectable neonicotinoid concentrations using Poisson's modified regression. Sampling strategies were accounted for in the regression models. RESULTS Detectable levels of acetamiprid were associated with a decrease in FMI (β = -3.17 kg/m2, 95% CI [-4.79, -1.54]), LMI (β = -3.17 kg/m2, 95% CI [-5.17, -1.17]), body fat percentage (β = -4.41, 95% CI [-8.20, -0.62]), waist circumference (β = -9.80 cm, 95% CI [-19.08, -0.51]), and BMI (β = -3.88kg/m2, 95% CI [-7.25, -0.51]) among adults. In contrast, detectable levels of 5-hydroxy-imidacloprid were associated with greater rates of being overweight/obese (IRR = 1.11, 95% CI [1.04, 1.18)) and increased LMI (β = 0.67 kg/m2, 95% CI [0.04, 1.29]). Sex modified the association between N-desmethyl-acetamiprid and LMI (pint = 0.075) with a positive association among males (β = 1.14 kg/m2, 95% CI [0.38, 1.90]), and an insignificant inverse association in females. Sex also modified the association for N-desmethyl-acetamiprid with FMI (pint = 0.095) and body fat percentage (pint = 0.072), with suggestive evidence showing positive associations for males and inverse associations for females. CONCLUSION Detectable concentrations of acetamiprid were inversely associated with adiposity, while there were mixed findings for 5-hydroxy-imidacloprid. Findings suggest sex differences, though results are not clear with regard to the directionality of the association by sex.
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Affiliation(s)
- Amruta M Godbole
- Department of Epidemiology and Biostatistics, University of Nevada Las Vegas, School of Public Health, Las Vegas, NV, United States
| | - Sheniz Moonie
- Department of Epidemiology and Biostatistics, University of Nevada Las Vegas, School of Public Health, Las Vegas, NV, United States
| | - Courtney Coughenour
- Department of Environmental and Occupational Health, University of Nevada Las Vegas, School of Public Health, Las Vegas, NV, United States
| | - Cai Zhang
- Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Aimin Chen
- Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
| | - Ann M Vuong
- Department of Epidemiology and Biostatistics, University of Nevada Las Vegas, School of Public Health, Las Vegas, NV, United States.
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Chen L, Su B, Zhang Y, Ma T, Liu J, Yang Z, Li Y, Gao D, Chen M, Ma Y, Wang X, Wen B, Jiang J, Dong Y, Song Y, Ma J. Association between height growth patterns in puberty and stature in late adolescence: A longitudinal analysis in chinese children and adolescents from 2006 to 2016. Front Endocrinol (Lausanne) 2022; 13:882840. [PMID: 35937794 PMCID: PMC9354934 DOI: 10.3389/fendo.2022.882840] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Accepted: 06/27/2022] [Indexed: 11/13/2022] Open
Abstract
Introduction The relationship between the characteristics of puberty growth and the stature (height and overweight and obesity) in late adolescence was not clear. We aimed to explore the effects of puberty growth patterns on the stature in late adolescence. Methods A total of 13,143 children from a longitudinal cohort from 2006 to 2016 in Zhongshan city of China were included. The Preece-Baines growth curve was fitted for each individual child, and the age at peak height velocity (APHV), peak height velocity (PHV), and age at take-off (TOA) were obtained from the Preece-Baines model. To compare the difference in height in late adolescence (at 18 years old) at different pubertal height growth patterns (height spurt timing, intensity, and duration), the height at baseline was matched by using the propensity score matching. The log-binomial model was applied to assess the association between the three pubertal height growth patterns (timing, intensity, and duration) and overweight and obesity status in late adolescence, controlling the urbanity and body mass index (BMI) at baseline. Results After matching the baseline height, boys and girls in three pubertal patterns with early timing (P < 0.01), small intensity (P < 0.01), and short duration (P < 0.01) of height spurt had the lowest final height in the late adolescence. A 16% increase and 45% increase of risk for overweight and obesity were significantly associated with the early APHV in boys and girls, respectively, relative risk (RR) in boys, 1.16(95% confidence interval, CI: 1.03-1.30), P = 0.011; RR in girls, 1.45(1.21-1.75), P < 0.001. A 21% increase and 59% increase of risk for overweight and obesity were significantly associated with small PHV in boys and girls, respectively, RR in boys, 1.21(1.07-1.36), P < 0.001; RR in girls, 1.59(1.30-1.95), P < 0.001; and an 80% increase of risk for overweight and obesity with small spurt duration in girls (RR = 1.80; 95% CI: 1.49, 2.18; P < 0.001). Conclusion Pubertal growth patterns, including earlier puberty onset timing, smaller puberty intensity, and shorter puberty spurt duration, had a positive association with lower height risks and higher overweight and obesity risks in late adolescence.
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Affiliation(s)
- Li Chen
- Institute of Child and Adolescent Health, School of Public Health, Peking University; National Health Commission Key Laboratory of Reproductive Health, Beijing, China
| | - Binbin Su
- Institute of Population Research, Peking University Asia-Pacific Economic Cooperation (APEC) Health Science Academy, Beijing, China
| | - Yi Zhang
- Institute of Child and Adolescent Health, School of Public Health, Peking University; National Health Commission Key Laboratory of Reproductive Health, Beijing, China
| | - Tao Ma
- Institute of Child and Adolescent Health, School of Public Health, Peking University; National Health Commission Key Laboratory of Reproductive Health, Beijing, China
| | - Jieyu Liu
- Institute of Child and Adolescent Health, School of Public Health, Peking University; National Health Commission Key Laboratory of Reproductive Health, Beijing, China
| | - Zhaogeng Yang
- Institute of Child and Adolescent Health, School of Public Health, Peking University; National Health Commission Key Laboratory of Reproductive Health, Beijing, China
| | - Yanhui Li
- Institute of Child and Adolescent Health, School of Public Health, Peking University; National Health Commission Key Laboratory of Reproductive Health, Beijing, China
| | - Di Gao
- Institute of Child and Adolescent Health, School of Public Health, Peking University; National Health Commission Key Laboratory of Reproductive Health, Beijing, China
| | - Manman Chen
- Institute of Child and Adolescent Health, School of Public Health, Peking University; National Health Commission Key Laboratory of Reproductive Health, Beijing, China
| | - Ying Ma
- Institute of Child and Adolescent Health, School of Public Health, Peking University; National Health Commission Key Laboratory of Reproductive Health, Beijing, China
| | - Xijie Wang
- Institute of Child and Adolescent Health, School of Public Health, Peking University; National Health Commission Key Laboratory of Reproductive Health, Beijing, China
- Vanke School of Public Health, Tsinghua University, Beijing, China
| | - Bo Wen
- School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia
| | - Jun Jiang
- Department of Atmospheric and Oceanic Science, Earth System Science Interdisciplinary Center, University of Maryland, College Park, MD, United States
| | - Yanhui Dong
- Institute of Child and Adolescent Health, School of Public Health, Peking University; National Health Commission Key Laboratory of Reproductive Health, Beijing, China
| | - Yi Song
- Institute of Child and Adolescent Health, School of Public Health, Peking University; National Health Commission Key Laboratory of Reproductive Health, Beijing, China
| | - Jun Ma
- Institute of Child and Adolescent Health, School of Public Health, Peking University; National Health Commission Key Laboratory of Reproductive Health, Beijing, China
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Parikh S, Parikh R, Michael K, Bikovski L, Barnabas G, Mardamshina M, Hemi R, Manich P, Goldstein N, Malcov-Brog H, Ben-Dov T, Glaich O, Liber D, Bornstein Y, Goltseker K, Ben-Bezalel R, Pavlovsky M, Golan T, Spitzer L, Matz H, Gonen P, Percik R, Leibou L, Perluk T, Ast G, Frand J, Brenner R, Ziv T, Khaled M, Ben-Eliyahu S, Barak S, Karnieli-Miller O, Levin E, Gepner Y, Weiss R, Pfluger P, Weller A, Levy C. Food-seeking behavior is triggered by skin ultraviolet exposure in males. Nat Metab 2022; 4:883-900. [PMID: 35817855 PMCID: PMC9314261 DOI: 10.1038/s42255-022-00587-9] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Accepted: 05/16/2022] [Indexed: 01/03/2023]
Abstract
Sexual dimorphisms are responsible for profound metabolic differences in health and behavior. Whether males and females react differently to environmental cues, such as solar ultraviolet (UV) exposure, is unknown. Here we show that solar exposure induces food-seeking behavior, food intake, and food-seeking behavior and food intake in men, but not in women, through epidemiological evidence of approximately 3,000 individuals throughout the year. In mice, UVB exposure leads to increased food-seeking behavior, food intake and weight gain, with a sexual dimorphism towards males. In both mice and human males, increased appetite is correlated with elevated levels of circulating ghrelin. Specifically, UVB irradiation leads to p53 transcriptional activation of ghrelin in skin adipocytes, while a conditional p53-knockout in mice abolishes UVB-induced ghrelin expression and food-seeking behavior. In females, estrogen interferes with the p53-chromatin interaction on the ghrelin promoter, thus blocking ghrelin and food-seeking behavior in response to UVB exposure. These results identify the skin as a major mediator of energy homeostasis and may lead to therapeutic opportunities for sex-based treatments of endocrine-related diseases.
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Affiliation(s)
- Shivang Parikh
- Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Roma Parikh
- Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Keren Michael
- Department of Human Services, The Max Stern Yezreel Valley Academic College, Yezreel Valley, Israel
| | - Lior Bikovski
- The Myers Neuro-Behavioral Core Facility, Tel Aviv University, Tel Aviv, Israel
- School of Behavioral Sciences, Netanya Academic College, Netanya, Israel
| | - Georgina Barnabas
- Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Mariya Mardamshina
- Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Rina Hemi
- Endocrine Service Unit, Sheba Medical Center Hospital, Tel Hashomer, Ramat Gan, Israel
| | - Paulee Manich
- Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Nir Goldstein
- School of Public Health, Sackler Faculty of Medicine and Sylvan Adams Sports Institute, Tel Aviv University, Tel Aviv, Israel
| | - Hagar Malcov-Brog
- Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Tom Ben-Dov
- Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Department of Otolaryngology, Head and Neck surgery, Meir Medical Center, Kfar Saba, Israel
| | - Ohad Glaich
- Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Daphna Liber
- Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Yael Bornstein
- School of Public Health, Sackler Faculty of Medicine and Sylvan Adams Sports Institute, Tel Aviv University, Tel Aviv, Israel
| | - Koral Goltseker
- Zuckerman Mind Brain Behavior Institute, Howard Hughes Medical Institute and Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA
| | - Roy Ben-Bezalel
- School of Zoology, Faculty of Life Science, Tel Aviv University, Tel Aviv, Israel
| | - Mor Pavlovsky
- Division of Dermatology, Tel Aviv Sourasky (Ichilov) Medical Center, Tel Aviv, Israel
| | - Tamar Golan
- Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Liron Spitzer
- Division of Dermatology, Tel Aviv Sourasky (Ichilov) Medical Center, Tel Aviv, Israel
| | - Hagit Matz
- Division of Dermatology, Tel Aviv Sourasky (Ichilov) Medical Center, Tel Aviv, Israel
- Phototherapy Unit, Assuta Medical Center, Tel Aviv, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Pinchas Gonen
- Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Ruth Percik
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
- Division of Endocrinology, Chaim Sheba Medical Center, Tel Hashomer, Israel
| | - Lior Leibou
- Department of Plastic and Reconstructive Surgery, E. Wolfson Medical Center, Holon, Israel
| | - Tomer Perluk
- Department of Plastic and Reconstructive Surgery, E. Wolfson Medical Center, Holon, Israel
| | - Gil Ast
- Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Jacob Frand
- Department of Plastic and Reconstructive Surgery, E. Wolfson Medical Center, Holon, Israel
| | - Ronen Brenner
- Institute of Oncology, E. Wolfson Medical Center, Holon, Israel
| | - Tamar Ziv
- The Smoler Proteomics Center, Lorry I. Lokey Interdisciplinary Center for Life Sciences and Engineering, Technion, Haifa, Israel
| | - Mehdi Khaled
- INSERM 1279, Gustave Roussy, Université Paris-Saclay, Villejuif, France
| | - Shamgar Ben-Eliyahu
- School of Psychological Sciences, Tel Aviv University, Tel Aviv, Israel
- Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel
| | - Segev Barak
- School of Psychological Sciences, Tel Aviv University, Tel Aviv, Israel
- Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel
| | - Orit Karnieli-Miller
- Department of Medical Education, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Eran Levin
- School of Zoology, Faculty of Life Science, Tel Aviv University, Tel Aviv, Israel
| | - Yftach Gepner
- School of Public Health, Sackler Faculty of Medicine and Sylvan Adams Sports Institute, Tel Aviv University, Tel Aviv, Israel
| | - Ram Weiss
- Department of Pediatrics, Ruth Rappaport Children's Hospital, Rambam Medical Center and Technion School of Medicine, Haifa, Israel
| | - Paul Pfluger
- Research Unit Neurobiology of Diabetes, Institute for Diabetes and Obesity, Helmholtz Zentrum München, German Centre for Diabetes Research (DZD), Neuherberg, Germany
| | - Aron Weller
- Department of Psychology and the Gonda Brain Research Center, Bar-Ilan University, Ramat Gan, Israel
| | - Carmit Levy
- Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
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Lei M, Qu X, Dai Z, Chen R, Zhu H, Shi Z. Effects of Caponization on Growth Performance and Carcass Composition of Yangzhou Ganders. Animals (Basel) 2022; 12:ani12111364. [PMID: 35681829 PMCID: PMC9179501 DOI: 10.3390/ani12111364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Revised: 05/18/2022] [Accepted: 05/23/2022] [Indexed: 11/17/2022] Open
Abstract
Simple Summary Goose meat is recognized as one of the healthiest foods. Goose capons are specially bred and consumed in several parts of China for their high-quality meat. However, the effects of caponization on goose growth and carcass traits have remained uninvestigated, and its molecular mechanisms remain unclear. In this research, caponization lowered testosterone and increased the total cholesterol and triglyceride concentrations in serum. Caponization increased live weights by promoting food intake and abdominal fat deposition, and improved meat quality by increasing intermuscular fat. Changes in the expression of these genes indicate that caponization increases the live weight mainly by increasing fat deposition rather than muscle growth. These results expand our understanding of the mechanisms of caponization on growth performance and fat deposition in ganders. Abstract In this study, we determined the effects of caponization on the growth performance and carcass traits of Yangzhou ganders. Fifty sham operated geese (the control group) and 80 caponized geese (the caponized group) were selected at 150 days of age and reared until 240 days of age. At 210 days of age, 30 geese from the caponized group were selected and fed with testosterone propionate (testosterone group). The results showed that caponization lowered testosterone and increased the total cholesterol and triglyceride concentrations in serum, live weights, average 15 day gains, and feed intake. Abdominal fat and intramuscular fat were significantly higher in the caponized geese than in the control at 240 days. Gene expression analysis showed that caponization promoted abdominal fat deposition and intermuscular fat content by upregulating the expression of adipogenic genes in the liver, adipose tissue, and muscle tissue. The high expression of SOCS3 in the hypothalamus, liver, and muscle of caponized geese suggests that caponization may lead to negative feedback regulation and leptin resistance. Changes in the expression of these genes, along with the downregulation of PAX3 in the breast muscle and MYOG in the leg muscles, indicate that caponization increases the live weight mainly by increasing fat deposition rather than muscle growth. These results expand our understanding of the mechanisms of caponization on growth performance and fat deposition in ganders.
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Affiliation(s)
- Mingming Lei
- Institute of Animal Science, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, China; (M.L.); (X.Q.); (Z.D.); (R.C.)
- Key Laboratory of Crop and Livestock Integration, Ministry of Agriculture, Nanjing 210014, China
| | - Xiaolu Qu
- Institute of Animal Science, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, China; (M.L.); (X.Q.); (Z.D.); (R.C.)
- Key Laboratory of Crop and Livestock Integration, Ministry of Agriculture, Nanjing 210014, China
| | - Zichun Dai
- Institute of Animal Science, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, China; (M.L.); (X.Q.); (Z.D.); (R.C.)
- Key Laboratory of Crop and Livestock Integration, Ministry of Agriculture, Nanjing 210014, China
| | - Rong Chen
- Institute of Animal Science, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, China; (M.L.); (X.Q.); (Z.D.); (R.C.)
- Key Laboratory of Crop and Livestock Integration, Ministry of Agriculture, Nanjing 210014, China
| | - Huanxi Zhu
- Institute of Animal Science, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, China; (M.L.); (X.Q.); (Z.D.); (R.C.)
- Key Laboratory of Crop and Livestock Integration, Ministry of Agriculture, Nanjing 210014, China
- Correspondence: (H.Z.); (Z.S.); Tel.: +86-025-8439-0346 (H.Z.); +86-025-8439-0956 (Z.S.)
| | - Zhendan Shi
- Institute of Animal Science, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, China; (M.L.); (X.Q.); (Z.D.); (R.C.)
- Key Laboratory of Crop and Livestock Integration, Ministry of Agriculture, Nanjing 210014, China
- Correspondence: (H.Z.); (Z.S.); Tel.: +86-025-8439-0346 (H.Z.); +86-025-8439-0956 (Z.S.)
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Rentzeperi E, Pegiou S, Koufakis T, Grammatiki M, Kotsa K. Sex Differences in Response to Treatment with Glucagon-like Peptide 1 Receptor Agonists: Opportunities for a Tailored Approach to Diabetes and Obesity Care. J Pers Med 2022; 12:jpm12030454. [PMID: 35330453 PMCID: PMC8950819 DOI: 10.3390/jpm12030454] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 03/02/2022] [Accepted: 03/10/2022] [Indexed: 02/04/2023] Open
Abstract
The available data suggest differences in the course of type 2 diabetes mellitus (T2DM) between men and women, influenced by the distinguishing features of the sex. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are a relatively new class of antidiabetic drugs that act by mimicking the function of endogenous glucagon-like peptide 1. They constitute valuable agents for the management of T2DM as, in addition to exerting a strong hypoglycemic action, they present cardiorenal protective properties, promote weight loss, and have a good safety profile, particularly with respect to the risk of hypoglycemia. Due to the precedent of studies having identified sexual dimorphic elements regarding the action of other antidiabetic agents, ongoing research has attempted to examine whether this is also the case for GLP-1 RAs. Until now, sex differences have been observed in the impact of GLP1-RAs on glycemic control, weight reduction, and frequency of adverse events. On the contrary, the question of whether these drugs differentially affect the two sexes with respect to cardiovascular risk and incidence of major adverse cardiovascular events remains under investigation. Knowledge of the potential sex-specific effects of these medications is extremely useful for the implementation of individualized therapeutic plans in the treatment of T2DM. This narrative review aims to present the available data regarding the sex-specific action of GLP-1 RAs as well as to discuss the potential pathophysiologic mechanisms explaining these dissimilarities.
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Hudson AD, Kauffman AS. Metabolic actions of kisspeptin signaling: Effects on body weight, energy expenditure, and feeding. Pharmacol Ther 2022; 231:107974. [PMID: 34530008 PMCID: PMC8884343 DOI: 10.1016/j.pharmthera.2021.107974] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Revised: 07/20/2021] [Accepted: 07/26/2021] [Indexed: 12/18/2022]
Abstract
Kisspeptin (encoded by the Kiss1 gene) and its receptor, KISS1R (encoded by the Kiss1r gene), have well-established roles in stimulating reproduction via central actions on reproductive neural circuits, but recent evidence suggests that kisspeptin signaling also influences metabolism and energy balance. Indeed, both Kiss1 and Kiss1r are expressed in many metabolically-relevant peripheral tissues, including both white and brown adipose tissue, the liver, and the pancreas, suggesting possible actions on these tissues or involvement in their physiology. In addition, there may be central actions of kisspeptin signaling, or factors co-released from kisspeptin neurons, that modulate metabolic, feeding, or thermoregulatory processes. Accumulating data from animal models suggests that kisspeptin signaling regulates a wide variety of metabolic parameters, including body weight and energy expenditure, adiposity and adipose tissue function, food intake, glucose metabolism, respiratory rates, locomotor activity, and thermoregulation. Herein, the current evidence for the involvement of kisspeptin signaling in each of these physiological parameters is reviewed, gaps in knowledge identified, and future avenues of important research highlighted. Collectively, the discussed findings highlight emerging non-reproductive actions of kisspeptin signaling in metabolism and energy balance, in addition to previously documented roles in reproductive control, but also emphasize the need for more research to resolve current controversies and uncover underlying molecular and physiological mechanisms.
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Affiliation(s)
- Alexandra D Hudson
- Dept. of OBGYN and Reproductive Sciences, University of California San Diego, La Jolla, CA 92093, United States of America
| | - Alexander S Kauffman
- Dept. of OBGYN and Reproductive Sciences, University of California San Diego, La Jolla, CA 92093, United States of America.
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Metabolic effects of the schizophrenia-associated 3q29 deletion. Transl Psychiatry 2022; 12:66. [PMID: 35177588 PMCID: PMC8854723 DOI: 10.1038/s41398-022-01824-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 01/14/2022] [Accepted: 01/21/2022] [Indexed: 11/09/2022] Open
Abstract
The 1.6 Mb 3q29 deletion is associated with developmental and psychiatric phenotypes, including a 40-fold increased risk for schizophrenia. Reduced birth weight and a high prevalence of feeding disorders in patients suggest underlying metabolic dysregulation. We investigated 3q29 deletion-induced metabolic changes using our previously generated heterozygous B6.Del16+/Bdh1-Tfrc mouse model. Animals were provided either standard chow (STD) or high-fat diet (HFD). Growth curves were performed on HFD mice to assess weight change (n = 30-50/group). Indirect calorimetry and untargeted metabolomics were performed on STD and HFD mice to evaluate metabolic phenotypes (n = 8-14/group). A behavioral battery was performed on STD and HFD mice to assess behavior change after the HFD challenge (n = 5-13/group). We found that B6.Del16+/Bdh1-Tfrc animals preferentially use dietary lipids as an energy source. Untargeted metabolomics of liver tissue showed a strong sex-dependent effect of the 3q29 deletion on fat metabolism. A HFD partially rescued the 3q29 deletion-associated weight deficit in females, but not males. Untargeted metabolomics of liver tissue after HFD revealed persistent fat metabolism alterations in females. The HFD did not affect B6.Del16+/Bdh1-Tfrc behavioral phenotypes, suggesting that 3q29 deletion-associated metabolic and behavioral outcomes are uncoupled. Our data suggest that dietary interventions to improve weight phenotypes in 3q29 deletion syndrome patients are unlikely to exacerbate behavioral manifestations. Our study also highlights the importance of assessing sex in metabolic studies and suggests that mechanisms underlying 3q29 deletion-associated metabolic phenotypes are sex-specific.
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Ni M, Zhang Q, Zhao J, Yao D, Wang T, Shen Q, Li W, Li B, Ding X, Liu Z. Prenatal inflammation causes obesity and abnormal lipid metabolism via impaired energy expenditure in male offspring. Nutr Metab (Lond) 2022; 19:8. [PMID: 35135573 PMCID: PMC8822840 DOI: 10.1186/s12986-022-00642-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Accepted: 01/08/2022] [Indexed: 12/17/2022] Open
Abstract
INTRODUCTION Obesity has becoming a global health issue. Fetus exposed to adversity in the uterine are susceptible to unhealth stimulus in adulthood. Prenatal inflammation is related to poor neonatal outcomes like neurodevelopmental impairments and respiratory complications. Recent studies suggested prenatal lipopolysaccharide (LPS) exposure could result in metabolic disorders. Thus, we hypothesized that offspring exposed to prenatal inflammation could develop into metabolic disorder. METHODS The pregnant C57BL/6J mice were intraperitoneally injected with 50 μg/kg LPS or saline only once at GD15. The male offspring were weighted weekly until sacrificed. Indirect calorimetry and body composition were both performed at 9 and 18 weeks old. At 20 weeks old, mice were fasted overnight before collecting blood samples and liver for metabolomics analysis and RNA sequencing, respectively. Differentially expressed genes were further verified by RT-qPCR and western blotting. RESULTS Prenatal inflammation resulted in obesity with increased fat percentage and decreased energy expenditure in middle-age male offspring. Abnormal lipid accumulation, changes of gene expression profile and upregulation of multi-component mechanistic target of rapamycin complex 1 (mTOR)/Peroxisome proliferator-activated receptor-γ pathway was observed in liver, accompanied with decreased bile acids level, unsaturated fatty acids androgens and prostaglandins in serum. Indirect calorimetry showed increased respiratory exchange rate and deceased spontaneous activity at 9 weeks in LPS group. Impaired energy expenditure was also observed at 18 weeks in LPS group. CONCLUSION Prenatal LPS exposure led to obesity and abnormal lipid metabolism through impaired energy expenditure.
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Affiliation(s)
- Meng Ni
- Departments of Neonatology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, 910# Hengshan Road, Shanghai, 20030, China
- International Peace Maternity and Child Health Hospital of China Welfare Institution, Shanghai, China
- Shanghai Key Laboratory of Embryo Original Disease, Shanghai, China
| | - Qianqian Zhang
- Departments of Neonatology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, 910# Hengshan Road, Shanghai, 20030, China
- International Peace Maternity and Child Health Hospital of China Welfare Institution, Shanghai, China
- Shanghai Key Laboratory of Embryo Original Disease, Shanghai, China
| | - Jiuru Zhao
- Departments of Neonatology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, 910# Hengshan Road, Shanghai, 20030, China
- International Peace Maternity and Child Health Hospital of China Welfare Institution, Shanghai, China
- Shanghai Key Laboratory of Embryo Original Disease, Shanghai, China
| | - Dongting Yao
- Departments of Neonatology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, 910# Hengshan Road, Shanghai, 20030, China
- International Peace Maternity and Child Health Hospital of China Welfare Institution, Shanghai, China
- Shanghai Key Laboratory of Embryo Original Disease, Shanghai, China
| | - Tao Wang
- Departments of Neonatology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, 910# Hengshan Road, Shanghai, 20030, China
- International Peace Maternity and Child Health Hospital of China Welfare Institution, Shanghai, China
- Shanghai Key Laboratory of Embryo Original Disease, Shanghai, China
| | - Qianwen Shen
- Departments of Neonatology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, 910# Hengshan Road, Shanghai, 20030, China
- International Peace Maternity and Child Health Hospital of China Welfare Institution, Shanghai, China
- Shanghai Key Laboratory of Embryo Original Disease, Shanghai, China
| | - Wei Li
- Departments of Neonatology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, 910# Hengshan Road, Shanghai, 20030, China
- International Peace Maternity and Child Health Hospital of China Welfare Institution, Shanghai, China
- Shanghai Key Laboratory of Embryo Original Disease, Shanghai, China
| | - Baihe Li
- Departments of Neonatology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, 910# Hengshan Road, Shanghai, 20030, China
- International Peace Maternity and Child Health Hospital of China Welfare Institution, Shanghai, China
- Shanghai Key Laboratory of Embryo Original Disease, Shanghai, China
| | - Xiya Ding
- Departments of Neonatology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, 910# Hengshan Road, Shanghai, 20030, China
- International Peace Maternity and Child Health Hospital of China Welfare Institution, Shanghai, China
- Shanghai Key Laboratory of Embryo Original Disease, Shanghai, China
| | - Zhiwei Liu
- Departments of Neonatology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, 910# Hengshan Road, Shanghai, 20030, China.
- International Peace Maternity and Child Health Hospital of China Welfare Institution, Shanghai, China.
- Shanghai Key Laboratory of Embryo Original Disease, Shanghai, China.
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The role of leptin and low testosterone in obesity. Int J Impot Res 2022; 34:704-713. [DOI: 10.1038/s41443-022-00534-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Accepted: 01/21/2022] [Indexed: 12/29/2022]
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Klaver M, van Velzen D, de Blok C, Nota N, Wiepjes C, Defreyne J, Schreiner T, Fisher A, Twisk J, Seidell J, T’Sjoen G, den Heijer M, de Mutsert R. Change in Visceral Fat and Total Body Fat and the Effect on Cardiometabolic Risk Factors During Transgender Hormone Therapy. J Clin Endocrinol Metab 2022; 107:e153-e164. [PMID: 34415999 PMCID: PMC8684493 DOI: 10.1210/clinem/dgab616] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Indexed: 11/19/2022]
Abstract
INTRODUCTION Excess visceral fat increases the risk of type 2 diabetes and cardiovascular disease and is influenced by sex hormones. Our aim was to investigate changes in visceral fat and the ratio of visceral fat to total body fat (VAT/TBF) and their associations with changes in lipids and insulin resistance after 1 year of hormone therapy in trans persons. METHODS In 179 trans women and 162 trans men, changes in total body and visceral fat estimated with dual-energy X-ray absorptiometry before and after 1 year of hormone therapy were related to lipids and insulin resistance [homeostatic model assessment of insulin resistance (HOMA-IR)] with linear regression analysis. RESULTS In trans women, total body fat increased by 4.0 kg (95% CI 3.4, 4.7), while the amount of visceral fat did not change (-2 grams; 95% CI -15, 11), albeit with a large range from -318 to 281, resulting in a decrease in the VAT/TBF ratio of 17% (95% CI 15, 19). In trans men, total body fat decreased with 2.8 kg (95% CI 2.2, 3.5), while the amount of visceral fat did not change (3 g; 95% CI -10, 16; range -372, 311), increasing the VAT/TBF ratio by 14% (95% CI 10, 17). In both groups, VAT/TBF was not associated with changes in blood lipids or HOMA-IR. CONCLUSIONS Hormone therapy in trans women and trans men resulted in changes in VAT/TBF, mainly due to changes in total body fat and were unrelated to changes in cardiometabolic risk factors, which suggests that any unfavorable cardiometabolic effects of hormone therapy are not mediated by changes in visceral fat or VAT/TBF.
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Affiliation(s)
- Maartje Klaver
- Department of Endocrinology and Center of Expertise on Gender Dysphoria, Amsterdam University Medical Center, Amsterdam, the Netherlands
| | - Daan van Velzen
- Department of Endocrinology and Center of Expertise on Gender Dysphoria, Amsterdam University Medical Center, Amsterdam, the Netherlands
| | - Christel de Blok
- Department of Endocrinology and Center of Expertise on Gender Dysphoria, Amsterdam University Medical Center, Amsterdam, the Netherlands
| | - Nienke Nota
- Department of Endocrinology and Center of Expertise on Gender Dysphoria, Amsterdam University Medical Center, Amsterdam, the Netherlands
| | - Chantal Wiepjes
- Department of Endocrinology and Center of Expertise on Gender Dysphoria, Amsterdam University Medical Center, Amsterdam, the Netherlands
| | - Justine Defreyne
- Department of Endocrinology, Ghent University Hospital, Ghent, Belgium
| | - Thomas Schreiner
- Department of Endocrinology, Oslo University Hospital, Oslo, Norway
| | - Alessandra Fisher
- Andrology, Women’s Endocrinology and Gender Incongruence Unit, University of Florence, Florence, Italy
| | - Jos Twisk
- Department of Clinical Epidemiology, Amsterdam University Medical Center, Amsterdam, the Netherlands
| | - Jaap Seidell
- Department of Health Sciences, Faculty of Science, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
| | - Guy T’Sjoen
- Department of Endocrinology, Ghent University Hospital, Ghent, Belgium
| | - Martin den Heijer
- Department of Endocrinology and Center of Expertise on Gender Dysphoria, Amsterdam University Medical Center, Amsterdam, the Netherlands
- Correspondence: Martin den Heijer, MD, PhD, Amsterdam University Medical Center, De Boelelaan 1107, 1081 HV, Amsterdam, The Netherlands.
| | - Renée de Mutsert
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands
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Huang J, Pham M, Panenka WJ, Honer WG, Barr AM. Chronic Treatment With Psilocybin Decreases Changes in Body Weight in a Rodent Model of Obesity. Front Psychiatry 2022; 13:891512. [PMID: 35664477 PMCID: PMC9157591 DOI: 10.3389/fpsyt.2022.891512] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Accepted: 04/27/2022] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND There are currently relatively few effective pharmacological treatments for obesity, and existing ones may be associated with limiting side-effects. In the search for novel anti-obesity agents, drugs that modify central serotonergic systems have historically proven to be effective in promoting weight loss. Psilocin, which is rapidly metabolized from psilocybin, is an agonist at multiple serotonin receptors. In the present study we assessed the effects of psilocybin and a positive control (metformin) on changes in body weight in a rat model of obesity. METHODS Five groups of adult male rats were pre-conditioned with a cafeteria diet until obese (>600 g) and then treated with either psilocybin (0.1, 1, or 5 mg/kg, i.p.), metformin (300 mg/kg, p.o.) or vehicle control. Treatments were for 27 consecutive weekdays, and body weights and high calorie food intake were recorded daily. Fasting glucose levels were recorded after 11 days of treatment. At the end of treatment rats completed a glucose tolerance test, and multiple fat pads were dissected out to assess adiposity. RESULTS The medium dose psilocybin group had to be terminated from the study prematurely. Both the low and high dose psilocybin groups caused a significant decrease in changes in body weight compared to controls. The metformin group produced a greater decrease in change in body weight than either psilocybin groups or controls. Both high dose psilocybin and metformin decreased consumption of the high calorie diet, and exhibited decreased central adiposity. CONCLUSION Psilocybin demonstrated modest but significant effects on weight gain. Further study is recommended.
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Affiliation(s)
- Joyce Huang
- Department of Anesthesiology, Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Michelle Pham
- Department of Anesthesiology, Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
| | - William J Panenka
- Department of Psychiatry, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.,British Columbia Mental Health & Substance Use Services Research Institute, Vancouver, BC, Canada
| | - William G Honer
- Department of Psychiatry, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.,British Columbia Mental Health & Substance Use Services Research Institute, Vancouver, BC, Canada
| | - Alasdair M Barr
- Department of Anesthesiology, Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.,British Columbia Mental Health & Substance Use Services Research Institute, Vancouver, BC, Canada
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Wang G, Li S, Li Y, Zhang M, Xu T, Li T, Cao L, Lu J. Corticosterone induces obesity partly via promoting intestinal cell proliferation and survival. Front Endocrinol (Lausanne) 2022; 13:1052487. [PMID: 36699046 PMCID: PMC9869250 DOI: 10.3389/fendo.2022.1052487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2022] [Accepted: 12/20/2022] [Indexed: 01/12/2023] Open
Abstract
INTRODUCTION A vicious cycle ensues whereby prolonged exposure to social stress causes increased production of glucocorticoids (GCs), leading to obesity even further. Understanding the role of GCs, the key element in the vicious circle, might be helpful to break the vicious circle. However, the mechanism by which GCs induce obesity remains elusive. METHODS Corticosterone (CORT) was administered to mice for 8 weeks. Food and water intake were recorded; obesity was analyzed by body-weight evaluation and magnetic resonance imaging (MRI); intestinal proliferation and survival were evaluated by H&E staining, EdU-progression test, TUNEL assay and immunofluorescence staining of Ki67 and CC3; RNA-seq was performed to analyze transcriptional alterations in small intestines and livers. RESULTS Chronic CORT treatment induced obesity, longer small intestines, hepatic steatosis and elevated levels of serum insulin and leptin in mice; CORT-treated mice showed increased cell proliferation and decreased apoptosis of small intestines; RNA-seq results indicate that differentially expressed genes (DEGs) were enriched in several cell growth/death-associated signaling pathways. DISCUSSION Herein we find that administration of CORT to mice promotes the proliferation and survival of intestinal cells, which might contribute to the longer small intestines and the elongated intestinal villi, thus leading to increased nutrient absorption and obesity in mice. Understanding CORT-induced alterations in intestines and associated signaling pathways might provide novel therapeutic clues for GCs or stress-associated obesity.
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Affiliation(s)
- Guanhao Wang
- Shanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China
- Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China
| | - Shuanqing Li
- Shanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China
| | - Yingqi Li
- Shanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China
- Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China
| | - Meihui Zhang
- Shanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China
| | - Ting Xu
- Shanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China
| | - Tianming Li
- Shanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China
| | - Lining Cao
- Shanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China
- *Correspondence: Jianfeng Lu, ; ; Lining Cao,
| | - Jianfeng Lu
- Shanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China
- Biomedical research center, Suzhou Institute of Tongji University, Suzhou, China
- *Correspondence: Jianfeng Lu, ; ; Lining Cao,
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Varghese M, Clemente J, Lerner A, Abrishami S, Islam M, Subbaiah P, Singer K. Monocyte Trafficking and Polarization Contribute to Sex Differences in Meta-Inflammation. Front Endocrinol (Lausanne) 2022; 13:826320. [PMID: 35422759 PMCID: PMC9001155 DOI: 10.3389/fendo.2022.826320] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Accepted: 02/24/2022] [Indexed: 11/13/2022] Open
Abstract
Obesity is associated with systemic inflammation and immune cell recruitment to metabolic tissues. Sex differences have been observed where male mice challenged with high fat diet (HFD) exhibit greater adipose tissue inflammation than females demonstrating a role for sex hormones in differential inflammatory responses. Circulating monocytes that respond to dietary lipids and chemokines and produce cytokines are the primary source of recruited adipose tissue macrophages (ATMs). In this study, we investigated sexual dimorphism in biological pathways in HFD-fed ATMs from male and female mice by RNA-seq. We also conducted chemotaxis assays to investigate sex differences in the migration of monocytes isolated from bone marrow from male and female mice toward a dietary saturated lipid - palmitate (PA), and a chemokine - monocyte chemoattractant protein 1 (MCP1), factors known to stimulate myeloid cells in obesity. ATM RNA-Seq demonstrated sex differences of both metabolic and inflammatory activation, including pathways for chemokine signaling and leukocyte trans-endothelial migration. In vivo monocyte transfer studies demonstrated that male monocytes traffic to female adipose tissue to generate ATMs more readily. In chemotaxis assays, lean male monocytes migrated in greater numbers than females toward PA and MCP1. With short-term HFD, male and female monocytes migrated similarly, but in chronic HFD, male monocytes showed greater migration than females upon PA and MCP1 stimulation. Studies with monocytes from toll-like receptor 4 knockout mice (Tlr4-/- ) demonstrated that both males and females showed decreased migration than WT in response to PA and MCP1 implying a role for TLR4 in monocyte influx in response to meta-inflammation. Overall, these data demonstrate the role of sexual dimorphism in monocyte recruitment and response to metabolic stimuli that may influence meta-inflammation in obesity.
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Affiliation(s)
- Mita Varghese
- Department of Pediatrics, Michigan Medicine, University of Michigan, Ann Arbor, MI, United States
| | - Jeremy Clemente
- Department of Pediatrics, Michigan Medicine, University of Michigan, Ann Arbor, MI, United States
| | - Arianna Lerner
- Department of Pediatrics, Michigan Medicine, University of Michigan, Ann Arbor, MI, United States
| | - Simin Abrishami
- Department of Pediatrics, Michigan Medicine, University of Michigan, Ann Arbor, MI, United States
| | - Mohammed Islam
- Department of Pediatrics, Michigan Medicine, University of Michigan, Ann Arbor, MI, United States
| | - Perla Subbaiah
- Department of Statistics and Mathematics, Oakland University, Rochester, MI, United States
| | - Kanakadurga Singer
- Department of Pediatrics, Michigan Medicine, University of Michigan, Ann Arbor, MI, United States
- *Correspondence: Kanakadurga Singer,
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Bjune JI, Strømland PP, Jersin RÅ, Mellgren G, Dankel SN. Metabolic and Epigenetic Regulation by Estrogen in Adipocytes. Front Endocrinol (Lausanne) 2022; 13:828780. [PMID: 35273571 PMCID: PMC8901598 DOI: 10.3389/fendo.2022.828780] [Citation(s) in RCA: 46] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Accepted: 01/24/2022] [Indexed: 12/12/2022] Open
Abstract
Sex hormones contribute to differences between males and females in body fat distribution and associated disease risk. Higher concentrations of estrogens are associated with a more gynoid body shape and with more fat storage on hips and thighs rather than in visceral depots. Estrogen-mediated protection against visceral adiposity is shown in post-menopausal women with lower levels of estrogens and the reduction in central body fat observed after treatment with hormone-replacement therapy. Estrogen exerts its physiological effects via the estrogen receptors (ERα, ERβ and GPR30) in target cells, including adipocytes. Studies in mice indicate that estrogen protects against adipose inflammation and fibrosis also before the onset of obesity. The mechanisms involved in estrogen-dependent body fat distribution are incompletely understood, but involve, e.g., increased mTOR signaling and suppression of autophagy and adipogenesis/lipid storage. Estrogen plays a key role in epigenetic regulation of adipogenic genes by interacting with enzymes that remodel DNA methylation and histone tail post-translational modifications. However, more studies are needed to map the differential epigenetic effects of ER in different adipocyte subtypes, including those in subcutaneous and visceral adipose tissues. We here review recent discoveries of ER-mediated transcriptional and epigenetic regulation in adipocytes, which may explain sexual dimorphisms in body fat distribution and obesity-related disease risk.
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Affiliation(s)
- Jan-Inge Bjune
- Hormone Laboratory, Department of Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway
- Mohn Nutrition Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Pouda Panahandeh Strømland
- Hormone Laboratory, Department of Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway
| | - Regine Åsen Jersin
- Hormone Laboratory, Department of Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway
- Mohn Nutrition Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Gunnar Mellgren
- Hormone Laboratory, Department of Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway
- Mohn Nutrition Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Simon Nitter Dankel
- Hormone Laboratory, Department of Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway
- Mohn Nutrition Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway
- *Correspondence: Simon Nitter Dankel,
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Ghaderpour S, Ghiasi R, Heydari H, Keyhanmanesh R. The relation between obesity, kisspeptin, leptin, and male fertility. Horm Mol Biol Clin Investig 2021; 43:235-247. [PMID: 34931507 DOI: 10.1515/hmbci-2021-0058] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Accepted: 11/22/2021] [Indexed: 11/15/2022]
Abstract
Over the past decades, obesity and infertility in men increased in parallel, and the association between both phenomena have been examined by several researchers. despite the fact that there is no agreement, obesity appears to affect the reproductive potential of men through various mechanisms, such as changes in the hypothalamic-pituitary-testicular (HPT) axis, spermatogenesis, sperm quality and/or alteration of sexual health. Leptin is a hormone produced by the adipose tissue, and its production elevates with increasing body fat. Many studies have supported the relationship between raised leptin production and reproductive function regulation. In fact, Leptin acts on the HPT axis in men at all levels. However, most obese men are insensitive to increased production of endogenous leptin and functional leptin resistance development. Recently, it has been recommended that Kisspeptin neurons mediate the leptin's effects on the reproductive system. Kisspeptin binding to its receptor on gonadotropin-releasing hormone (GnRH) neurons, activates the mammal's reproductive axis and stimulates GnRH release. Increasing infertility associated with obesity is probably mediated by the Kisspeptin-GnRH pathway. In this review, the link between obesity, kisspeptin, leptin, and male fertility will be discussed.
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Affiliation(s)
- Saber Ghaderpour
- Department of Physiology, Tabriz Faculty of Medical Science, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Rafighe Ghiasi
- Department of Physiology, Tabriz Faculty of Medical Science, Tabriz University of Medical Sciences, Tabriz, Iran.,Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hamed Heydari
- Department of Physiology, Tabriz Faculty of Medical Science, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Rana Keyhanmanesh
- Department of Physiology, Tabriz Faculty of Medical Science, Tabriz University of Medical Sciences, Tabriz, Iran.,Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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de Alencar AKN, Wang H, de Oliveira GMM, Sun X, Zapata-Sudo G, Groban L. Crossroads between Estrogen Loss, Obesity, and Heart Failure with Preserved Ejection Fraction. Arq Bras Cardiol 2021; 117:1191-1201. [PMID: 34644788 PMCID: PMC8757160 DOI: 10.36660/abc.20200855] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Revised: 12/16/2020] [Accepted: 01/27/2021] [Indexed: 11/24/2022] Open
Abstract
The prevalence of obesity and heart failure with preserved ejection fraction (HFpEF) increases significantly in postmenopausal women. Although obesity is a risk factor for left ventricular diastolic dysfunction (LVDD), the mechanisms that link the cessation of ovarian hormone production, and particularly estrogens, to the development of obesity, LVDD, and HFpEF in aging females are unclear. Clinical, and epidemiologic studies show that postmenopausal women with abdominal obesity (defined by waist circumference) are at greater risk for developing HFpEF than men or women without abdominal obesity. The study presents a review of clinical data that support a mechanistic link between estrogen loss plus obesity and left ventricular remodeling with LVDD. It also seeks to discuss potential cell and molecular mechanisms for estrogen-mediated protection against adverse adipocyte cell types, tissue depots, function, and metabolism that may contribute to LVDD and HFpEF.
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Affiliation(s)
| | - Hao Wang
- Wake Forest School of MedicineDepartments of AnesthesiologyWinston-SalemNorth CarolinaEstados Unidos da AméricaWake Forest School of Medicine - Departments of Anesthesiology, Winston-Salem, North Carolina - Estados Unidos da América
- Wake Forest School of MedicineWinston-SalemNorth CarolinaEstados Unidos da AméricaWake Forest School of Medicine - Internal Medicine-Section of Molecular Medicine, Winston-Salem, North Carolina - Estados Unidos da América
| | - Gláucia Maria Moraes de Oliveira
- Universidade Federal do Rio de JaneiroDepartamento de Clínica MédicaFaculdade de MedicinaRio de JaneiroRJBrasilUniversidade Federal do Rio de Janeiro - Departamento de Clínica Médica, Faculdade de Medicina, Rio de Janeiro, RJ - Brasil
| | - Xuming Sun
- Wake Forest School of MedicineDepartments of AnesthesiologyWinston-SalemNorth CarolinaEstados Unidos da AméricaWake Forest School of Medicine - Departments of Anesthesiology, Winston-Salem, North Carolina - Estados Unidos da América
| | - Gisele Zapata-Sudo
- Universidade Federal do Rio de JaneiroInstituto de Ciências BiomédicasRio de JaneiroRJBrasilUniversidade Federal do Rio de Janeiro - Instituto de Ciências Biomédicas, Rio de Janeiro, RJ - Brasil
- Universidade Federal do Rio de JaneiroInstituto de Cardiologia Edson SaadFaculdade de MedicinaRio de JaneiroRJBrasilUniversidade Federal do Rio de Janeiro - Instituto de Cardiologia Edson Saad, Faculdade de Medicina, Rio de Janeiro, RJ - Brasil
| | - Leanne Groban
- Wake Forest School of MedicineDepartments of AnesthesiologyWinston-SalemNorth CarolinaEstados Unidos da AméricaWake Forest School of Medicine - Departments of Anesthesiology, Winston-Salem, North Carolina - Estados Unidos da América
- Wake Forest School of MedicineWinston-SalemNorth CarolinaEstados Unidos da AméricaWake Forest School of Medicine - Internal Medicine-Section of Molecular Medicine, Winston-Salem, North Carolina - Estados Unidos da América
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Katzer K, Hill JL, McIver KB, Foster MT. Lipedema and the Potential Role of Estrogen in Excessive Adipose Tissue Accumulation. Int J Mol Sci 2021; 22:ijms222111720. [PMID: 34769153 PMCID: PMC8583809 DOI: 10.3390/ijms222111720] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Revised: 10/25/2021] [Accepted: 10/26/2021] [Indexed: 12/26/2022] Open
Abstract
Lipedema is a painful fat disorder that affects ~11% of the female population. It is characterized by bilateral, disproportionate accumulation of subcutaneous adipose tissue predominantly in the lower body. The onset of lipedema pathophysiology is thought to occur during periods of hormonal fluctuation, such as puberty, pregnancy, or menopause. Although the identification and characterization of lipedema have improved, the underlying disease etiology remains to be elucidated. Estrogen, a key regulator of adipocyte lipid and glucose metabolism, and female-associated body fat distribution are postulated to play a contributory role in the pathophysiology of lipedema. Dysregulation of adipose tissue accumulation via estrogen signaling likely occurs by two mechanisms: (1). altered adipocyte estrogen receptor distribution (ERα/ERß ratio) and subsequent metabolic signaling and/or (2). increased release of adipocyte-produced steroidogenic enzymes leading to increased paracrine estrogen release. These alterations could result in increased activation of peroxisome proliferator-activated receptor γ (PPARγ), free fatty acid entry into adipocytes, glucose uptake, and angiogenesis while decreasing lipolysis, mitochondriogenesis, and mitochondrial function. Together, these metabolic alterations would lead to increased adipogenesis and adipocyte lipid deposition, resulting in increased adipose depot mass. This review summarizes research characterizing estrogen-mediated adipose tissue metabolism and its possible relation to excessive adipose tissue accumulation associated with lipedema.
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Identification of candidate genes from androgenic gland in Macrobrachium nipponense regulated by eyestalk ablation. Sci Rep 2021; 11:19855. [PMID: 34615913 PMCID: PMC8494903 DOI: 10.1038/s41598-021-99022-4] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Accepted: 09/17/2021] [Indexed: 11/28/2022] Open
Abstract
The eyestalk of crustaceans, such as Macrobrachium nipponense, contains many neurosecretory hormones affecting the process of reproduction, molting, metabolism of glucose, and other functions. In this study, important metabolic pathways and candidate genes involved in male sexual development were selected from M. nipponense. The methodology involved performing long-read and next generation transcriptome sequencing of genes from the androgenic gland after eyestalk ablation. qPCR analysis revealed that the mRNA expression of Mn-IAG was significantly increased after ablation of both the single-side (SS) and double-side (DS) eyestalk, compared with the control group (CG). The long-read transcriptome generated 49,840 non-redundant transcripts. A total of 1319, 2092 and 4351 differentially expressed genes (DEGs) were identified between CG versus SS, SS versus DS and CG versus DS, respectively. These data indicated that ablation of the double-sided eyestalk played stronger regulatory roles than the single-side ablation on male sexual development in M. nipponense. This was consistent with the qPCR analysis. Cell Cycle, Cellular Senescence, Oxidative Phosphorylation, Glycolysis/Gluconeogenesis and Steroid Hormone Biosynthesis were the primary enriched metabolic pathways in all three comparisons, and the important genes from these metabolic pathways were also selected. qPCR permitted secondary confirmation of ten DEGs identified through RNA-seq. RNAi-mediated silencing analyses of Hydroxysteroid dehydrogenase like 1 (HSDL1) revealed that HSDL1 has a positive regulatory effect on testes development. This study provides valuable insight into male sexual development in M. nipponense, including metabolic pathways and genes, paving the way for advanced studies on male sexual development in this species and in other crustaceans.
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Bo T, Wen J, Gao W, Tang L, Liu M, Wang D. Influence of HFD-induced precocious puberty on neurodevelopment in mice. Nutr Metab (Lond) 2021; 18:86. [PMID: 34530850 PMCID: PMC8447761 DOI: 10.1186/s12986-021-00604-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2021] [Accepted: 07/29/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Precocious puberty is frequently associated with obesity, which will lead to long-term effects, especially on growth and reproduction. However, the effect of precocious puberty on children's neurodevelopment is still unknown. OBJECTIVES Here we evaluated the effect of High fat diet (HFD)-induced precocious puberty on neurodevelopment and behaviors of animals. METHODS Ovaries sections were stained with hematoxylin-eosin (H&E) using standard techniques. Behavioral tests included elevated plus maze (EPM), open field exploration, Y-Maze, marble burying test, and novelty- suppressed feeding. The expression of genes related to puberty and neural development was detected by immunohistochemistry and Western blot. RESULTS Our results showed HFD-induced precocious puberty increased the risk-taking behavior and decreased memory of mice. The content of Tyrosine hydroxylase (TH) and Arginine vasopressin (AVP) in hypothalamus were higher in HFD group than control group. Although the recovery of normal diet will gradually restore the body fat and other physiological index of mice, the anxiety increases in adult mice, and the memory is also damaged. CONCLUSIONS These findings describe the sensitivity of mice brain to HFD-induced precocious puberty and the irrecoverability of neural damage caused by precocious puberty. Therefore, avoiding HFD in childhood is important to prevent precocious puberty and neurodevelopmental impairment in mice.
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Affiliation(s)
- Tingbei Bo
- State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.,CAS Center for Excellence in Biotic Interactions, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Jing Wen
- College of Life and Environmental Science, Wenzhou University, Wenzhou, 325035, China
| | - Wenting Gao
- State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.,CAS Center for Excellence in Biotic Interactions, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Liqiu Tang
- State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.,CAS Center for Excellence in Biotic Interactions, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Min Liu
- State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.,CAS Center for Excellence in Biotic Interactions, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Dehua Wang
- State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China. .,School of Life Science, Shandong University, Qingdao, 266237, China. .,CAS Center for Excellence in Biotic Interactions, University of Chinese Academy of Sciences, Beijing, 100049, China.
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Cardiovascular Properties of the Androgen-Induced PCOS Model in Rats: The Role of Oxidative Stress. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2021; 2021:8862878. [PMID: 34512871 PMCID: PMC8426083 DOI: 10.1155/2021/8862878] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Revised: 01/13/2021] [Accepted: 08/16/2021] [Indexed: 01/24/2023]
Abstract
Polycystic ovary syndrome (PCOS) is a multifaced reproductive endocrinopathy affecting 6-20% of women of childbearing age. It was previously shown that women with PCOS have an increased risk of cardiovascular (CV) diseases. The aim of this study was to evaluate the cardiodynamic parameters of isolated rats' hearts, blood pressure levels, and histomorphological changes in the heart tissue following the androgen-induced PCOS model in rats and the role of oxidative stress in the development of these CV properties of PCOS. 21-day-old female rats (n = 12) were divided into control and PCOS groups. PCOS was induced by administration of testosterone enanthate (1 mg/kg BW, daily) during 35 days. During the autoregulation protocol (40-120 mmHg) on the Langendorff apparatus, ex vivo cardiodynamic parameters of retrogradely perfused hearts showed enhanced contractile function and increased lusitropic effects in the left ventricle (LV) in PCOS rats. Systolic and diastolic pressures in LV were elevated at all perfusion pressure values. Systemic arterial systolic blood pressure showed borderline elevation, while mean arterial blood pressure was significantly higher in PCOS rats. Histological evaluation of heart tissue depicted hypertrophic (8.3%) alterations in LV cardiomyocytes and increase (7.3%) in LV wall thickness. Oxidative stress parameters were altered in systemic circulation, coronary venous effluent (CVE), and heart tissue. Levels of superoxide dismutase and reduced glutathione were decreased in blood and heart tissue, while catalase activity was not altered. Degree of lipid peroxidation was increased in circulation as well as heart tissue. Increased levels of O2− in CVE indicated the cardiotoxic effects in the rat PCOS model. The mentioned alterations of oxidative stress parameters in the blood, CVE, and heart could be recommended as potential contributors underlying the development of CV risk in PCOS women.
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Age and Sex: Impact on adipose tissue metabolism and inflammation. Mech Ageing Dev 2021; 199:111563. [PMID: 34474078 DOI: 10.1016/j.mad.2021.111563] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 08/19/2021] [Accepted: 08/26/2021] [Indexed: 02/08/2023]
Abstract
Age associated chronic inflammation is a major contributor to diseases with advancing age. Adipose tissue function is at the nexus of processes contributing to age-related metabolic disease and mediating longevity. Hormonal fluctuations in aging potentially regulate age-associated visceral adiposity and metabolic dysfunction. Visceral adiposity in aging is linked to aberrant adipogenesis, insulin resistance, lipotoxicity and altered adipokine secretion. Age-related inflammatory phenomena depict sex differences in macrophage polarization, changes in T and B cell numbers, and types of dendritic cells. Sex differences are also observed in adipose tissue remodeling and cellular senescence suggesting a role for sex steroid hormones in the regulation of the adipose tissue microenvironment. It is crucial to investigate sex differences in aging clinical outcomes to identify and better understand physiology in at-risk individuals. Early interventions aimed at targets involved in adipose tissue adipogenesis, remodeling and inflammation in aging could facilitate a profound impact on health span and overcome age-related functional decline.
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Özay AC, Özay ÖE. The importance of inflammation markers in polycystic ovary syndrome. ACTA ACUST UNITED AC 2021; 67:411-417. [PMID: 34468607 DOI: 10.1590/1806-9282.20200860] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Accepted: 10/22/2020] [Indexed: 11/22/2022]
Abstract
OBJECTIVE This study aimed to examine inflammation markers in patients with polycystic ovary syndrome (PCOS) and to compare them with healthy women. METHODS This prospective study was conducted by examining patients who applied to the Near East University Gynecology and Obstetrics Outpatient Clinic between January 2019 and January 2020. A total of 110 PCOS patients with 135 control groups were compared in terms of metabolism, hormonal factors, and inflammation markers. RESULTS The neutrophil count, neutrophil-lymphocyte ratio (NLR), platelet, platelet-lymphocyte ratio (PLR), platelecrit (PCT), erythrocyte cell distribution width, platelet distribution width, mean platelet volume, and C-reactive protein (CRP) values were found to be statistically significantly higher in patients with PCOS. There was a positive correlation between inflammation markers and serum androgens. Also, a positive correlation was observed between inflammation markers and cardiovascular risk parameters. In receiver operating characteristic curve analysis, the most valuable parameter in distinguishing PCOS patients from healthy controls was serum CRP levels [areas under the curve (AUC)=0.928, 95%CI 0.894-0.963, p<0.001, 92.6% sensitivity, and 82.7% specificity]. CONCLUSIONS Serum CRP, neutrophil count, and PCT and NLR levels are valuable markers that show the inflammatory process in PCOS patients.
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Affiliation(s)
- Ali Cenk Özay
- Near East University Hospital, Department of Obstetrics and Gynecology - Nicosia, Chipre
| | - Özlen Emekçi Özay
- Near East University, Research Center of Experimental Health Sciences - Nicosia, Chipre
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Pawłowski B, Żelaźniewicz A. The evolution of perennially enlarged breasts in women: a critical review and a novel hypothesis. Biol Rev Camb Philos Soc 2021; 96:2794-2809. [PMID: 34254729 DOI: 10.1111/brv.12778] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Revised: 07/02/2021] [Accepted: 07/02/2021] [Indexed: 12/15/2022]
Abstract
The possession of permanent, adipose breasts in women is a uniquely human trait that develops during puberty, well in advance of the first pregnancy. The adaptive role and developmental pattern of this breast morphology, unusual among primates, remains an unresolved conundrum. The evolutionary origins of this trait have been the focus of many hypotheses, which variously suggest that breasts are a product of sexual selection or of natural selection due to their putative role in assisting in nursing or as a thermoregulatory organ. Alternative hypotheses assume that permanent breasts are a by-product of other evolutionary changes. We review and evaluate these hypotheses in the light of recent literature on breast morphology, physiology, phylogeny, ontogeny, sex differences, and genetics in order to highlight their strengths and flaws and to propose a coherent perspective and a new hypothesis on the evolutionary origins of perennially enlarged breasts in women. We propose that breasts appeared as early as Homo ergaster, originally as a by-product of other coincident evolutionary processes of adaptive significance. These included an increase in subcutaneous fat tissue (SFT) in response to the demands of thermoregulatory and energy storage, and of the ontogenetic development of the evolving brain. An increase in SFT triggered an increase in oestradiol levels (E2). An increase in meat in the diet of early Homo allowed for further hormonal changes, such as greater dehydroepiandrosterone (DHEA/S) synthesis, which were crucial for brain evolution. DHEA/S is also easily converted to E2 in E2-sensitive body parts, such as breasts and gluteofemoral regions, causing fat accumulation in these regions, enabling the evolution of perennially enlarged breasts. Furthermore, it is also plausible that after enlarged breasts appeared, they were co-opted for other functions, such as attracting mates and indicating biological condition. Finally, we argue that the multifold adaptive benefits of SFT increase and hormonal changes outweighed the possible costs of perennially enlarged breasts, enabling their further development.
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Affiliation(s)
- Bogusław Pawłowski
- Department of Human Biology, University of Wrocław, ul. Przybyszewskiego 63, Wrocław, 51-148, Poland
| | - Agnieszka Żelaźniewicz
- Department of Human Biology, University of Wrocław, ul. Przybyszewskiego 63, Wrocław, 51-148, Poland
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