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Zarrin V, Taherizadeh M, Tanideh N, Rahmani-Moghadam E, Talaei-Khozani T. Persian Gulf brown seaweed extracts showing anti-obesity potency on adipogenic differentiation in human adipose-derived mesenchymal stem cells and obese male rats. Obes Res Clin Pract 2025:S1871-403X(25)00037-7. [PMID: 40222851 DOI: 10.1016/j.orcp.2025.02.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2023] [Revised: 06/10/2024] [Accepted: 02/27/2025] [Indexed: 04/15/2025]
Abstract
The objectives of this study were to compare the effects of two Persian Gulf marine algae, Padina pavonica (Pp) and Sargassum angustifolium (Sa), on both in vitro and in vivo models. Hot water and Ethanolic extracts of Pp (HWE.Pp, EE.Pp) and Sa (HWE.Sa, EE.Sa) were added to human adipose-derived mesenchymal stem cells (hADMSCs) cultures treated with adipogenic medium. An in vivo study was done by feeding the extracts to the high-fat diet (HFD) male Wistar rats. A decrease in adipocyte differentiation, and an increase in leptin production and energy loss as indicated by UCP1 and UCP3 upregulation and intracellular glucose content were detected. Weight loss, food intake reduction, downregulation of the PPARγ, and upregulation of UCP1, UCP3, FNDC5, and leptin were observed in the animals were fed with both algae compared to untreated obese and normal rats. Both extracts with superiority of Sa also normalized the level of blood sugar, cholesterol, triglyceride, low-density lipoprotein (LDL), high-density lipoprotein (HDL), as well as inflammatory factors and liver enzymes. HW-Sa was the best extract to normalize all the criteria. Sa can be considered as a good remedy for losing weight by inhibiting adipocyte differentiation, and inflammation, increasing energy loss, and decreasing food intake through leptin elevation.
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Affiliation(s)
- Vahideh Zarrin
- Tissue Engineering Lab, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammreza Taherizadeh
- Department of Marine Biology, Faculty of Marine Science and Technology, University of Hormozgan, Bandar Abbas, Iran.
| | - Nader Tanideh
- Stem Cells Technology Research Center, pharmacology department, Shiraz University of Medical Sciences, shiraz, Iran.
| | - Ebrahim Rahmani-Moghadam
- Anatomy Department, Shiraz medical School, Shiraz University of Medical Sciences, Zand street, Shiraz, Iran
| | - Tahereh Talaei-Khozani
- Histomorphometry and Stereology Research Center, anatomy department, School of Medicine, Shiraz University of Medical Sciences, Imam Hussain Square, Zand St., Shiraz, Iran.
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Xie W, Hong Y, Chen X, Wang S, Zhang F, Chi X. Waist-to-hip ratio and nonalcoholic fatty liver disease: a clinical observational and Mendelian randomization analysis. Front Nutr 2024; 11:1426749. [PMID: 39555187 PMCID: PMC11563977 DOI: 10.3389/fnut.2024.1426749] [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: 05/02/2024] [Accepted: 10/08/2024] [Indexed: 11/19/2024] Open
Abstract
Background Obesity often coincides with non-alcoholic fatty liver disease (NAFLD), yet a significant portion of NAFLD patients exhibit normal body mass index (BMI) but have abdominal obesity. Recognizing this discrepancy, we aimed to delve deeper into this phenomenon through observational studies coupled with two-sample Mendelian randomization (MR) analysis, with waist-to-hip ratio (WHR) serving as the indicator for abdominal obesity. Our objective was to ascertain whether WHR correlates with an increased risk of NAFLD development. Methods This study utilized data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 to examine the association between WHR and NAFLD through weighted multivariate logistic regression models. On this basis, subgroup analyses were performed to further explore the correlation between WHR and NAFLD. Subsequently, a two-sample MR analysis was conducted using genome-wide association studies (GWAS) data to investigate the potential causal relationship between WHR and NAFLD. Sensitivity analyses were also employed to ensure the robustness of our findings. Results A total of 3,732 eligible participants were included in the analysis. Weighted multivariable-adjusted logistic regression models revealed a positive association between WHR and the risk of NAFLD (Q2vsQ1: OR = 1.94 [95% CI: 1.55-2.44]; Q3vsQ1: OR = 2.08 [95% CI: 1.51-2.85]; Q4vsQ1: OR = 3.70 [95% CI: 2.13-6.43], p < 0.05). The results of the subgroup analysis suggested that there was an interaction in the correlation between WHR and NAFLD in normal weight, overweight, and obese populations (p < 0.05). The RCS curves indicated that there was a nonlinear relationship between WHR and NAFLD in populations with BMI in the normal versus obese categories. Furthermore, MR analysis provided additional support for the causal relationship between WHR and NAFLD. Using inverse variance weighting (IVW), the MR analysis yielded an OR of 2.062 (95% CI: 1.680-2.531, p<0.05). Consistent results were obtained with the other four MR methods, all supporting the same direction of causality. Sensitivity analyses were performed to assess the robustness of the findings (p > 0.5), further reinforcing the reliability of the observed associations. Conclusion WHR elevation heightens the susceptibility to NAFLD.
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Affiliation(s)
- Weining Xie
- The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China
- Infectious Disease Department, Guangdong Provincial Hospital of Integrated Traditional Chinese and Western Medicine, Foshan, Guangdong Province, China
| | - Yan Hong
- Affiliated Guangdong Hospital of Integrated Traditional Chinese and Western Medicine of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Foshan, Guangdong Province, China
| | - Xinrong Chen
- The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China
| | - Shujuan Wang
- Affiliated Guangdong Hospital of Integrated Traditional Chinese and Western Medicine of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Foshan, Guangdong Province, China
| | - Fan Zhang
- Affiliated Guangdong Hospital of Integrated Traditional Chinese and Western Medicine of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Foshan, Guangdong Province, China
| | - Xiaoling Chi
- The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China
- Department of Hepatology, Guangdong Province Hospital of Traditional Chinese Medicine, Guangzhou, Guangdong Province, China
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Son WH, Park HT, Jeon BH, Ha MS. Effects of fermented oyster extract supplementation on free fatty acid and liver enzymes in older women with obesity. Phys Act Nutr 2024; 28:58-63. [PMID: 39501695 PMCID: PMC11540988 DOI: 10.20463/pan.2024.0024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 09/02/2024] [Accepted: 09/30/2024] [Indexed: 11/09/2024] Open
Abstract
PURPOSE This study aimed to investigate the effects of a 12-week intake of fermented oyster extract on free fatty acids and liver enzymes in older women with obesity and to provide basic data for improving liver function in older individuals with obesity. METHODS A randomized, double-blind, placebo-controlled clinical trial aimed to confirm the effects of fermented oyster extract intake on free fatty acid (FFA) levels and liver function in older women with obesity. The study included 40 older women with obesity with a body mass index ≥ 25 kg/m2. Participants were divided into a fermented oyster intake group (n = 20) and control group (n = 20). Serum FFA, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT) levels were measured at weeks 0 and 12. RESULTS Our results showed an interaction effect between the two groups in terms of serum FFA levels (p<0.05), with a post-intervention decrease in the FSO group (p<0.05). AST, ALT, and GGT levels also showed an interaction effect between the two groups (p<0.05), with a significant postintervention decrease in the FSO group (p<0.05). CONCLUSION The intake of fermented oyster extract significantly reduced FFA, ALT, AST, and GGT levels. These results suggested that the consumption of fermented oyster extract may improve liver function. However, the findings of this study were limited to elderly women with obesity, and the relatively short intake period and small sample size may limit the generalization of the results.
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Affiliation(s)
- Woo Hyeon Son
- Institute of Convergence Bio-Health, Dong-A University, Busan, Republic of Korea
| | - Hyun Tae Park
- Graduate School of Health Care and Sciences, College of Health Science, Dong-A University, Busan, Republic of Korea
| | - Byeong Hwan Jeon
- Department of Sports and Health Science, College of Arts, Kyungsung University, Busan, Republic of Korea
| | - Min-Seong Ha
- Laboratory of Sports Conditioning: Nutrition Biochemistry and Neuroscience, Department of Sport Science, College of Arts and Sports, University of Seoul, Seoul, Republic of Korea
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Ning M, Xu A, Zeng R, Xue J, Wang B, Liu X. The effect of overweight/obesity and FTO gene polymorphism on liver function-related parameters in Chinese adolescents. THE NATIONAL MEDICAL JOURNAL OF INDIA 2024; 37:248-252. [PMID: 39953885 DOI: 10.25259/nmji_264_2022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/17/2025]
Abstract
Background Overweight/obesity is an important risk factor for liver disease, affecting changes in liver function-related parameters. The fat mass and obesity associated (FTO) gene has been reported to have a link between overweight/obesity and liver fat metabolism. We studied the association of FTO rs9939609 variants with liver function-related parameters and overweight/obesity in Chinese adolescents aged 16 to 26 as freshmen. Methods We examined rs9939609 polymorphisms in 198 control and 173 overweight/obese people, and the genotypes of the samples were analyzed by Sanger sequencing. We investigated the effects of FTO gene polymorphism on overweight/obesity and liver function-related parameters. Results The values of aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) in overweight/obesity group were significantly higher than those in control group. The rs9939609 AA genotype increased the risk of overweight/obesity by 3.45 times independent of body mass index (BMI) compared with TT genotype, the rs9939609 (AA) genotype was significantly associated with AST and ALT. Conclusion FTO rs9939609 variants were associated with overweight/obesity and overweight/obesity has a significant influence on the increased liver function-related parameters. The rs9939609 (AA) positively correlated with AST and ALT levels. Overweight/obese patients should pay more attention to liver function-related parameters.
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Affiliation(s)
- Meiwei Ning
- Department of Laboratory Medicine, Heilongjiang University of Chinese Medicine Jiamusi College, Jiamusi, 154007, China
| | - Aohong Xu
- Department of Laboratory Medicine, Center for Medical Experiments (CME), Guangming District People's Hospital, Shenzhen, 518106, China
| | - Rong Zeng
- Department of Laboratory Medicine, Hubei University of Chinese Medicine, Hongshan District, Wuhan, Hubei, China
| | - Jinruo Xue
- Department of Laboratory Medicine, Hubei University of Chinese Medicine, Hongshan District, Wuhan, Hubei, China
| | - Boda Wang
- Clinical Laboratory, Huangjiahu Hospital of Hubei University of Chinese Medicine, Wuhan, China
| | - Xiang Liu
- Department of Laboratory Medicine, Hubei University of Chinese Medicine, Hongshan District, Wuhan, Hubei, China
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Chung GE, Jeong S, Yu SJ, Yoo J, Cho Y, Lee K, Shin DW, Kim YJ, Yoon J, Han K, Cho EJ. Gamma-glutamyl transferase and the risk of all-cause and disease-specific mortality in patients with diabetes: A nationwide cohort study. J Diabetes 2024; 16:e13551. [PMID: 38664890 PMCID: PMC11045922 DOI: 10.1111/1753-0407.13551] [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] [Revised: 02/07/2024] [Accepted: 02/16/2024] [Indexed: 04/29/2024] Open
Abstract
BACKGROUND There exists a paucity of data regarding whether gamma-glutamyl transferase is associated with disease-specific mortality in patients with type 2 diabetes mellitus. This study aimed to investigate the association of serum gamma-glutamyl transferase levels with all-cause and disease-specific mortality in patients with diabetes mellitus using a Korean nationwide health-screening database. METHODS A total of 9 687 066 patients without viral hepatitis or liver cirrhosis who underwent health examination in 2009 were included. These patients were divided into four groups according to sex-specific quartiles of serum gamma-glutamyl transferase levels. RESULTS During a median follow-up period of 8.1 years, 222 242 deaths were identified. The all-cause mortality rate increased as the serum gamma-glutamyl transferase levels became higher (highest quartile vs lowest quartile: hazard ratio [HR], 1.57; 95% confidence interval [CI], 1.55-1.59; p for trend <.001). Similar trends were observed for cardiovascular disease (HR, 1.57; 95% CI, 1.53-1.62), ischemic heart disease (HR, 1.40; 95% CI, 1.33-1.48), and stroke (HR, 1.72; 95% CI, 1.60-1.85) in the highest quartile, as compared with the lowest quartile (p for trend <.001). As the gamma-glutamyl transferase quartiles became higher, mortality rates related to cancer (HR, 1.56; 95% CI, 1.52-1.60), liver disease (HR, 9.42; 95% CI, 8.81-10.07), respiratory disease (HR, 1.55; 95% CI, 1.49-1.62), and infectious disease (HR, 1.73; 95% CI, 1.59-1.87) also increased in the highest quartile, compared with the lowest quartile (p for trend <.001). CONCLUSIONS Serum gamma-glutamyl transferase levels may be useful for the risk assessment of all-cause and disease-specific mortality among patients with type 2 diabetes mellitus.
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Affiliation(s)
- Goh Eun Chung
- Department of Internal Medicine and Healthcare Research InstituteSeoul National University Hospital Healthcare System Gangnam CenterSeoulRepublic of Korea
| | - Su‐Min Jeong
- Department of MedicineSeoul National University College of MedicineSeoulRepublic of Korea
| | - Su Jong Yu
- Department of Internal Medicine and Liver Research InstituteSeoul National University College of MedicineSeoulRepublic of Korea
| | - Jeong‐Ju Yoo
- Department of Internal Medicine, Division of Gastroenterology and HepatologySoonchunhyang University Bucheon HospitalGyeonggi‐doRepublic of Korea
| | - Yuri Cho
- Center for Liver and Pancreatobiliary CancerNational Cancer CenterGoyangRepublic of Korea
| | - Kyu‐na Lee
- Department of Biomedicine & Health ScienceThe Catholic University of KoreaSeoulKorea
| | - Dong Wook Shin
- Department of MedicineSeoul National University College of MedicineSeoulRepublic of Korea
- Department of Clinical Research Design and Evaluation/Department of Digital HealthSamsung Advanced Institute for Health ScienceSeoulRepublic of Korea
| | - Yoon Jun Kim
- Department of Internal Medicine and Healthcare Research InstituteSeoul National University Hospital Healthcare System Gangnam CenterSeoulRepublic of Korea
| | - Jung‐Hwan Yoon
- Department of Internal Medicine and Healthcare Research InstituteSeoul National University Hospital Healthcare System Gangnam CenterSeoulRepublic of Korea
| | - Kyungdo Han
- Department of BiostatisticsCollege of Medicine, Soongsil UniversitySeoulRepublic of Korea
| | - Eun Ju Cho
- Department of Internal Medicine and Liver Research InstituteSeoul National University College of MedicineSeoulRepublic of Korea
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Gopalakrishna H, Nair GB, Roghani RS, Ravendhran N, Rotman Y. Optimizing surveillance of low-risk metabolic dysfunction associated steatotic liver disease using transient elastography. Eur J Gastroenterol Hepatol 2024; 36:476-481. [PMID: 38407839 PMCID: PMC10923068 DOI: 10.1097/meg.0000000000002713] [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] [Indexed: 02/27/2024]
Abstract
BACKGROUND Most people with metabolic dysfunction-associated steatotic liver disease (MASLD) lack significant fibrosis and are considered low-risk. Surveillance strategy for low-risk MASLD remains uncertain. AIM Identify which low-risk subjects can avoid follow-up vibration-controlled transient elastography (VCTE) within 1 year. METHODS Retrospective analysis of two independent low-risk MASLD cohorts (baseline liver stiffness [LS] < 8kPa) with routine 6-12 months follow-up VCTE. The primary outcome was LS ≥ 8kPa on follow-up, requiring referral and further work-up according to current guidance. Predictors of the primary outcome on univariate and multivariate logistic regression were incorporated into a decision algorithm, and validated in an independent cohort. RESULTS Of 206 subjects in the derivation cohort, 96 were low-risk. After a median of 10 months, 24 (25%) low-risk subjects had LS ≥ 8kPa. Baseline LS ( P < 0.01) and ALT change from baseline ( P = 0.02) (multivariate AUROC = 0.84 [0.74-0.94]) predicted the primary outcome, and were incorporated to a two-step decision algorithm. Low-risk subjects with baseline LS < 5.5 kPa can avoid repeating VCTE in a year, while those with LS > 6.8 kPa require one. For intermediate baseline LS (5.5-6.8kPa), repeat VCTE is only indicated when ALT increase > 6 U/L. The algorithm had 92% negative predictive value, 78% specificity, and 78% accuracy in the derivation cohort. In the validation cohort (n = 64), it had 91% NPV, 72% specificity, and 71% accuracy. CONCLUSION In low-risk MASLD, a simple algorithm combining baseline LS and ALT change can be used to safely avoid a repeat VCTE in a year.
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Affiliation(s)
- Harish Gopalakrishna
- Liver & Energy Metabolism Section, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
| | - Gayatri B Nair
- Department of Pulmonary and Sleep Medicine, Medstar Georgetown University Hospital, Washington DC, USA
| | - Roham Salman Roghani
- Liver & Energy Metabolism Section, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
- Department of Internal Medicine, Eisenhower Health, Rancho Mirage, CA, USA
| | - Natarajan Ravendhran
- Digestive Disease Associates, Baltimore, MD, USA
- Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA
| | - Yaron Rotman
- Liver & Energy Metabolism Section, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
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Liu L, Lin J, Yin M, Liu L, Gao J, Liu X, Zhu J, Wu A. Association of the fat mass index with hepatic steatosis and fibrosis: evidence from NHANES 2017-2018. Sci Rep 2024; 14:6943. [PMID: 38521854 PMCID: PMC10960854 DOI: 10.1038/s41598-024-57388-1] [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: 01/14/2024] [Accepted: 03/18/2024] [Indexed: 03/25/2024] Open
Abstract
Limited population-based studies discuss the association between fat mass index (FMI) and the risk of liver diseases. This investigation utilized data from the National Health and Nutrition Examination Survey (NHANES) to examine the linkage between the FMI and liver conditions, specifically steatosis and fibrosis. The study leveraged data from NHANES's 2017-2018 cross-sectional study, employing an oversampling technique to deal with sample imbalance. Hepatic steatosis and fibrosis were identified by vibration-controlled transient elastography. Receiver operating curve was used to assess the relationship of anthropometric indicators, e.g., the FMI, body mass index (BMI), weight-adjusted-waist index (WWI), percentage of body fat (BF%), waist-to-hip ratio (WHR), and appendicular skeletal muscle index (ASMI), with hepatic steatosis and fibrosis. In this study, which included 2260 participants, multivariate logistic regression models, stratified analyses, restricted cubic spline (RCS), and sharp regression discontinuity analyses were utilized. The results indicated that the WHR and the FMI achieved the highest area under the curve for identifying hepatic steatosis and fibrosis, respectively (0.720 and 0.726). Notably, the FMI presented the highest adjusted odds ratio for both hepatic steatosis (6.40 [4.91-8.38], p = 2.34e-42) and fibrosis (6.06 [5.00, 7.37], p = 5.88e-74). Additionally, potential interaction effects were observed between the FMI and variables such as the family income-to-poverty ratio, smoking status, and hypertension, all of which correlated with the presence of liver fibrosis (p for interaction < 0.05). The RCS models further confirmed a significant positive correlation of the FMI with the controlled attenuation parameter and liver stiffness measurements. Overall, the findings underscore the strong link between the FMI and liver conditions, proposing the FMI as a potential straightforward marker for identifying liver diseases.
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Affiliation(s)
- Lihe Liu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China
- Suzhou Clinical Center of Digestive Diseases, Suzhou, 215006, China
| | - Jiaxi Lin
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China
- Suzhou Clinical Center of Digestive Diseases, Suzhou, 215006, China
| | - Minyue Yin
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Lu Liu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China
- Suzhou Clinical Center of Digestive Diseases, Suzhou, 215006, China
| | - Jingwen Gao
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China
- Suzhou Clinical Center of Digestive Diseases, Suzhou, 215006, China
| | - Xiaolin Liu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China
- Suzhou Clinical Center of Digestive Diseases, Suzhou, 215006, China
| | - Jinzhou Zhu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
- Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
| | - Airong Wu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
- Suzhou Clinical Center of Digestive Diseases, Suzhou, 215006, China.
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Sawamoto A, Okada M, Matsuoka N, Okuyama S, Nakajima M. Tipepidine activates AMPK and improves adipose tissue fibrosis and glucose intolerance in high-fat diet-induced obese mice. FASEB J 2024; 38:e23542. [PMID: 38466234 DOI: 10.1096/fj.202301861rr] [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: 09/12/2023] [Revised: 02/13/2024] [Accepted: 02/23/2024] [Indexed: 03/12/2024]
Abstract
Tipepidine (3-[di-2-thienylmethylene]-1-methylpiperidine) (TP) is a non-narcotic antitussive used in Japan. Recently, the potential application of TP in the treatment of neuropsychiatric disorders, such as depression and attention deficit hyperactivity disorder, has been suggested; however, its functions in energy metabolism are unknown. Here, we demonstrate that TP exhibits a metabolism-improving action. The administration of TP reduced high-fat diet-induced body weight gain in mice and lipid accumulation in the liver and increased the weight of epididymal white adipose tissue (eWAT) in diet-induced obese (DIO) mice. Furthermore, TP inhibited obesity-induced fibrosis in the eWAT. We also found that TP induced AMP-activated protein kinase (AMPK) activation in the eWAT of DIO mice and 3T3-L1 cells. TP-induced AMPK activation was abrogated by the transfection of liver kinase B1 siRNA in 3T3-L1 cells. The metabolic effects of TP were almost equivalent to those of metformin, an AMPK activator that is used as a first-line antidiabetic drug. In summary, TP is a potent AMPK activator, suggesting its novel role as an antidiabetic drug owing to its antifibrotic effect on adipose tissues.
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Affiliation(s)
- Atsushi Sawamoto
- Department of Pharmaceutical Pharmacology, College of Pharmaceutical Sciences, Matsuyama University, Matsuyama, Ehime, Japan
| | - Madoka Okada
- Department of Pharmaceutical Pharmacology, College of Pharmaceutical Sciences, Matsuyama University, Matsuyama, Ehime, Japan
| | - Nanako Matsuoka
- Department of Pharmaceutical Pharmacology, College of Pharmaceutical Sciences, Matsuyama University, Matsuyama, Ehime, Japan
| | - Satoshi Okuyama
- Department of Pharmaceutical Pharmacology, College of Pharmaceutical Sciences, Matsuyama University, Matsuyama, Ehime, Japan
| | - Mitsunari Nakajima
- Department of Pharmaceutical Pharmacology, College of Pharmaceutical Sciences, Matsuyama University, Matsuyama, Ehime, Japan
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Zhao Y, Jiao F, Tang T, Wu S, Wang F, Zhao X. Adverse effects and potential mechanisms of fluxapyroxad in Xenopus laevis on carbohydrate and lipid metabolism. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2023:121710. [PMID: 37137408 DOI: 10.1016/j.envpol.2023.121710] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/07/2023] [Revised: 03/21/2023] [Accepted: 04/22/2023] [Indexed: 05/05/2023]
Abstract
Fungicides are one of significant contributing factors to the rapid decline of amphibian species worldwide. Fluxapyroxad (FLX), an effective and broad-spectrum succinate dehydrogenase inhibitor fungicide, has attracted major concerns due to its long-lasting in the environment. However, the potential toxicity of FLX in the development of amphibians remains mostly unknown. In this research, the potential toxic effects and mechanisms of FLX on Xenopus laevis were investigated. In the acute toxicity test, the 96 h median lethal concentration (LC50) of FLX to X. laevis tadpoles was 1.645 mg/L. Based on the acute toxicity result, tadpoles at the stage 51 were exposed to 0, 0.00822, 0.0822, and 0.822 mg/L FLX during 21 days. Results demonstrated that FLX exposure led to an apparent delay in the growth and development of tadpoles and associated with severe liver injury. Additionally, FLX induced glycogen depletion and lipid accumulation in the liver of X. laevis. The biochemical analysis of plasma and liver indicated that FLX exposure could perturb liver glucose and lipid homeostasis by altering enzyme activity related to glycolysis, gluconeogenesis, fatty acid synthesis, and oxidation. Consistent with the biochemical result, FLX exposure altered the liver transcriptome profile, and the enrichment analysis of differential expression genes highlighted the adverse effects of FLX exposure on steroid biosynthesis, PPAR signaling pathway, glycolysis/gluconeogenesis, and fatty acid metabolism in the tadpole liver. Overall, our study was the first to reveal that sub-lethal concentrations of FLX could induce liver damage and produce obvious interference effects on carbohydrate and lipid metabolism of Xenopus, providing new insight into the potential chronic hazards of FLX for amphibians.
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Affiliation(s)
- Yang Zhao
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Key Laboratory for Pesticide Residue Detection of Ministry of Agriculture and Rural Affairs, Institute of Agro-Product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, China
| | - Fang Jiao
- College of Marine Sciences, South China Agricultural University, Guangzhou, 510640, China
| | - Tao Tang
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Key Laboratory for Pesticide Residue Detection of Ministry of Agriculture and Rural Affairs, Institute of Agro-Product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, China
| | - Shenggan Wu
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Key Laboratory for Pesticide Residue Detection of Ministry of Agriculture and Rural Affairs, Institute of Agro-Product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, China
| | - Feidi Wang
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Key Laboratory for Pesticide Residue Detection of Ministry of Agriculture and Rural Affairs, Institute of Agro-Product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, China
| | - Xueping Zhao
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Key Laboratory for Pesticide Residue Detection of Ministry of Agriculture and Rural Affairs, Institute of Agro-Product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, China.
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Jeon J, Lee S, Oh C. Age-specific risk factors for the prediction of obesity using a machine learning approach. Front Public Health 2023; 10:998782. [PMID: 36733276 PMCID: PMC9887184 DOI: 10.3389/fpubh.2022.998782] [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: 07/21/2022] [Accepted: 12/06/2022] [Indexed: 01/18/2023] Open
Abstract
Machine Learning is a powerful tool to discover hidden information and relationships in various data-driven research fields. Obesity is an extremely complex topic, involving biological, physiological, psychological, and environmental factors. One successful approach to the topic is machine learning frameworks, which can reveal complex and essential risk factors of obesity. Over the last two decades, the obese population (BMI of above 23) in Korea has grown. The purpose of this study is to identify risk factors that predict obesity using machine learning classifiers and identify the algorithm with the best accuracy among classifiers used for obesity prediction. This work will allow people to assess obesity risk from blood tests and blood pressure data based on the KNHANES, which used data constructed by the annual survey. Our data include a total of 21,100 participants (male 10,000 and female 11,100). We assess obesity prediction by utilizing six machine learning algorithms. We explore age- and gender-specific risk factors of obesity for adults (19-79 years old). Our results highlight the four most significant features in all age-gender groups for predicting obesity: triglycerides, ALT (SGPT), glycated hemoglobin, and uric acid. Our findings show that the risk factors for obesity are sensitive to age and gender under different machine learning algorithms. Performance is highest for the 19-39 age group of both genders, with over 70% accuracy and AUC, while the 60-79 age group shows around 65% accuracy and AUC. For the 40-59 age groups, the proposed algorithm achieved over 70% in AUC, but for the female participants, it achieved lower than 70% accuracy. For all classifiers and age groups, there is no big difference in the accuracy ratio when the number of features is more than six; however, the accuracy ratio decreased in the female 19-39 age group.
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Affiliation(s)
- Junhwi Jeon
- Department of Applied Mathematics, Kyung Hee University, Yongin, South Korea
| | - Sunmi Lee
- Department of Applied Mathematics, Kyung Hee University, Yongin, South Korea
| | - Chunyoung Oh
- Department of Mathematics Education, Chonnam National University, Gwangju, South Korea,*Correspondence: Chunyoung Oh ✉
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11
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Zhang S, Wang L, Yu M, Guan W, Yuan J. Fat mass index as a screening tool for the assessment of non-alcoholic fatty liver disease. Sci Rep 2022; 12:20219. [PMID: 36418352 PMCID: PMC9684573 DOI: 10.1038/s41598-022-23729-1] [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] [Subscribe] [Scholar Register] [Received: 12/18/2021] [Accepted: 11/04/2022] [Indexed: 11/25/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is replacing hepatitis B as the leading cause of chronic liver disease in China. The purpose of this study is to select good tools to identify NAFLD from the body composition, anthropometry and related routine clinical parameters. A total of 5076 steelworkers, aged 22-60 years, was included in this study. Body fat mass was measured via bioelectrical impedance analysis (BIA) and fat mass index (FMI) was derived. Ultrasonography method was used to detect hepatic steatosis. Random forest classifier and best subset regression were used to select useful parameters or models that can accurately identify NAFLD. Receiver operating characteristic (ROC) curves were used to describe and compare the performance of different diagnostic indicators and algorithms including fatty liver index (FLI) and hepatic steatosis index (HSI) in NAFLD screening. ROC analysis indicated that FMI can be used with high accuracy to identify heavy steatosis as determined by ultrasonography in male workers [area under the curve (AUC) 0.95, 95% CI 0.93-0.98, sensitivity 89.0%, specificity 91.4%]. The ability of single FMI to identify NAFLD is no less than that of combination panels, even better than the combination panel of HSI. The best subset regression model that including FMI, waist circumference, and serum levels of triglyceride and alanine aminotransferase has moderate accuracy in diagnosing overall NAFLD (AUC 0.83). FMI and the NAFLD best subset (BIC) score seem to be good tools to identify NAFLD in Chinese steelworkers.
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Affiliation(s)
- Shengkui Zhang
- Department of Epidemiology and Health Statistics, School of Public Health, North China University of Science and Technology, 21 Bohai Road, Caofeidian Xincheng, Tangshan, 063210, Hebei, China
- Department of Epidemiology and Health Statistics, School of Basic Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100730, China
| | - Lihua Wang
- Department of Epidemiology and Health Statistics, School of Public Health, North China University of Science and Technology, 21 Bohai Road, Caofeidian Xincheng, Tangshan, 063210, Hebei, China
| | - Miao Yu
- Department of Epidemiology and Health Statistics, School of Public Health, North China University of Science and Technology, 21 Bohai Road, Caofeidian Xincheng, Tangshan, 063210, Hebei, China
| | - Weijun Guan
- Department of Epidemiology and Health Statistics, School of Public Health, North China University of Science and Technology, 21 Bohai Road, Caofeidian Xincheng, Tangshan, 063210, Hebei, China
| | - Juxiang Yuan
- Department of Epidemiology and Health Statistics, School of Public Health, North China University of Science and Technology, 21 Bohai Road, Caofeidian Xincheng, Tangshan, 063210, Hebei, China.
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12
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Sini ZK, Afzalpour ME, Ahmadi MM, Sardar MA, Khaleghzadeh H, Gorgani-Firuzjaee S, Akaras E, Azimkhani A. Comparison of the effects of high-intensity interval training and moderate-intensity continuous training on indices of liver and muscle tissue in high-fat diet-induced male rats with non-alcoholic fatty liver disease. EGYPTIAN LIVER JOURNAL 2022. [DOI: 10.1186/s43066-022-00229-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Abstract
Background
Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver diseases. It is shown that moderate to high physical activities can play a crucial role in improving this disease.
Aim
The purpose of this study was to explore the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on the levels of the myonectin in serum and tissue levels and fatty acid transport protein 4 (FATP4) in male rats with NAFLD.
Materials and methods
Thirty-three male rats were randomly divided into five groups: high-fat diet to confirm NAFLD induction (n = 5), normal diet sedentary (n = 7), high-fat diet sedentary (n = 7), high-fat diet with HIIT (n = 7), and high-fat diet with MCIT (n = 7). Induction of NAFLD was performed by feeding rats for 12 weeks with a high-fat diet containing 60% fat. The training protocols were performed in five sessions per week for 8 weeks. The HIIT group has performed 4 × 4 min interval running on a treadmill up to 80–95% maximal oxygen uptake (VO2max) and then recovered at 50–60% VO2max. The MICT protocol has performed up to 50–60% VO2max for 50 min. myonectin and FATP4 were also measured by the animal Elisa kit (Zellbio, Germany) with a sensitivity of 0.02 ng/L. Insulin resistance was evaluated by the insulin resistance homeostasis assessment index using the following formula (HOMA-IR): “fasting glucose (mg/dl) × fasting in insulin (mg/L) ÷ 405”. One-way ANOVA analysis of variance was utilized for statistical analyses and Tukey’s post hoc test at a significant level of p < 0.05.
Results
The 8-week intervention showed that both HIIT and MICT positively influenced the serum myonectin and FATP4 levels (p < 0.05). Moreover, there was a significant difference between the trained groups in tissue levels of the myonectin and serum levels of FATP4 (p < 0.05).
Conclusions
Altogether, both HIIT and MICT can lead to valuable adaptations and recovery of NAFLD in male rats.
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Abdelnabi MN, Flores Molina M, Soucy G, Quoc-Huy Trinh V, Bédard N, Mazouz S, Jouvet N, Dion J, Tran S, Bilodeau M, Estall JL, Shoukry NH. Sex-Dependent Hepatoprotective Role of IL-22 Receptor Signaling in Non-Alcoholic Fatty Liver Disease-Related Fibrosis. Cell Mol Gastroenterol Hepatol 2022; 14:1269-1294. [PMID: 35970323 PMCID: PMC9596743 DOI: 10.1016/j.jcmgh.2022.08.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Revised: 08/07/2022] [Accepted: 08/08/2022] [Indexed: 01/31/2023]
Abstract
BACKGROUND & AIMS Nonalcoholic fatty liver disease (NAFLD) is a major health problem with complex pathogenesis. Although sex differences in NAFLD pathogenesis have been reported, the mechanisms underlying such differences remain understudied. Interleukin (IL)22 is a pleiotropic cytokine with both protective and/or pathogenic effects during liver injury. IL22 was shown to be hepatoprotective in NAFLD-related liver injury. However, these studies relied primarily on exogenous administration of IL22 and did not examine the sex-dependent effect of IL22. Here, we sought to characterize the role of endogenous IL22-receptor signaling during NAFLD-induced liver injury in males and females. METHODS We used immunofluorescence, flow cytometry, histopathologic assessment, and gene expression analysis to examine IL22 production and characterize the intrahepatic immune landscape in human subjects with NAFLD (n = 20; 11 men and 9 women) and in an in vivo Western high-fat diet-induced NAFLD model in IL22RA knock out mice and their wild-type littermates. RESULTS Examination of publicly available data sets from 2 cohorts with NAFLD showed increased hepatic IL22 gene expression in females compared with males. Furthermore, our immunofluorescence analysis of liver sections from NAFLD subjects (n = 20) showed increased infiltration of IL22-producing cells in females. Similarly, IL22-producing cells were increased in wild-type female mice with NAFLD and the hepatic IL22/IL22 binding protein messenger RNA ratio correlated with expression of anti-apoptosis genes. The lack of endogenous IL22-receptor signaling (IL22RA knockout) led to exacerbated liver damage, inflammation, apoptosis, and liver fibrosis in female, but not male, mice with NAFLD. CONCLUSIONS Our data suggest a sex-dependent hepatoprotective antiapoptotic effect of IL22-receptor signaling during NAFLD-related liver injury in females.
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Affiliation(s)
- Mohamed N Abdelnabi
- Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada; Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université de Montréal, Montréal, Québec, Canada
| | - Manuel Flores Molina
- Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada; Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université de Montréal, Montréal, Québec, Canada
| | - Geneviève Soucy
- Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada; Département de Département de Pathologie et Biologie Cellulaire, Faculté de Médecine, Université de Montréal, Montréal, Québec, Canada
| | - Vincent Quoc-Huy Trinh
- Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada; Département de Département de Pathologie et Biologie Cellulaire, Faculté de Médecine, Université de Montréal, Montréal, Québec, Canada
| | - Nathalie Bédard
- Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada; Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université de Montréal, Montréal, Québec, Canada
| | - Sabrina Mazouz
- Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada; Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université de Montréal, Montréal, Québec, Canada
| | - Nathalie Jouvet
- Institut de Recherches, Cliniques de Montreal, Montréal, Québec, Canada
| | - Jessica Dion
- Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada; Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université de Montréal, Montréal, Québec, Canada
| | - Sarah Tran
- Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada; Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université de Montréal, Montréal, Québec, Canada
| | - Marc Bilodeau
- Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada; Département de Médecine, Faculté de Médecine, Université de Montréal, Montréal, Québec, Canada
| | - Jennifer L Estall
- Institut de Recherches, Cliniques de Montreal, Montréal, Québec, Canada; Département de Médecine, Faculté de Médecine, Université de Montréal, Montréal, Québec, Canada
| | - Naglaa H Shoukry
- Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada; Département de Médecine, Faculté de Médecine, Université de Montréal, Montréal, Québec, Canada.
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Tandoroost A, Moradi S, Moradinazar M, Moradi S, Pasdar Y, Nayebi A, Marzbani B. Body composition and risk of non-alcoholic fatty liver disease: A case control study. MEDITERRANEAN JOURNAL OF NUTRITION AND METABOLISM 2022. [DOI: 10.3233/mnm-210570] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND: While evidence has been a highlight that obesity may be associated with the increased incidence of Nonalcoholic fatty liver disease (NAFLD), these data have depended on defective measures of obesity such as body mass index (BMI), and usually have not the well-known relationship between body composition with NAFLD. METHODS: In a case-control study of people aged 20– 65 years, we directly measured body composition (using bioelectrical impedance analysis), height, weight, and waist and hip circumferences who referred to radiology clinics in Kermanshah, Iran. Dietary intake was assessed by the food frequency questionnaire (FFQ). RESULTS: Among 221 people examined, 103 cases with NAFLD and 119 as control were established. The risk of NAFLD was positively associated with higher BMI and the components of the body composition. These associations were strengthened after adjusting for potential confounders including gender, age, marital status, education, smoking, alcohol consumption, and physical activity CONCLUSION: An increasing prevalence of obesity may be associated with the increasing incidence of NAFLD as observed in many populations. We observed an increased risk of NAFLD associated with increased BMI, central adiposity, and the fat component of weight, but found no association with nonfat mass.
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Affiliation(s)
- Arash Tandoroost
- Student Research Committee, Faculty of Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sara Moradi
- Student Research Committee, Faculty of Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mehdi Moradinazar
- Research Center for Environmental Determinants ofHealth (RCEDH), Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Shima Moradi
- Department of Nutritional Sciences, School of Nutritional Sciences and Food Technology, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Yahya Pasdar
- Department of Nutritional Sciences, School of Nutritional Sciences and Food Technology, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Atiyeh Nayebi
- Department of Nutritional Sciences, School of Nutritional Sciences and Food Technology, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Behjat Marzbani
- Research Center for Environmental Determinants ofHealth (RCEDH), Kermanshah University of Medical Sciences, Kermanshah, Iran
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15
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CANDER S, ÖZ GÜL Ö. Investigation of serum neprilysin levels in overweight and normal weight young women. TURKISH JOURNAL OF INTERNAL MEDICINE 2022. [DOI: 10.46310/tjim.1070422] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
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16
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Clapp B, Dodoo C, Kim J, Castro C, Wicker E, Mandania R, Davis B. Safety of liver biopsy at the time of bariatric surgery: an analysis of the MBSAQIP database. Surg Endosc 2022; 36:413-421. [PMID: 33483847 DOI: 10.1007/s00464-021-08297-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Accepted: 01/05/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND The majority of patients undergoing bariatric surgery have hepatic steatosis. Liver biopsy is not technically difficult to perform at the time of metabolic and bariatric surgery (MBS), but there may be concerns for bleeding complications. The safety of liver biopsy (LBx) at the time of MBS has been studied in single institutional studies but has not been studied on a national level. METHODS The MBSAQIP database for 2015-2018 was examined. The codes for Roux-en-Y gastric bypass (RYGB) of 43644 and sleeve gastrectomy (SG) 43775 were used along with 47000 (percutaneous liver biopsy), 47001 (percutaneous liver biopsy at time of other procedure), and 47379 (unlisted laparoscopic procedure, liver). Outcomes such as operative time, complications, and length of stay were examined. Propensity-matched analysis was performed to evaluate for adjusted associations. RESULTS There were 546,532 patients that met our inclusion criteria. Of those, 21,367 (3.9%) underwent LBx. Only 5.5% (8012) of patients undergoing RYGB had a LBx and 3.3% (13,355) of SG patients. Patients who underwent a LBx had a longer operative time before (103 min vs 84 min, p < 0.001) and after propensity matching [regression coefficient (RC): 10.7 (8.87, 12.5)]. There was no increase in length of stay. There was an increased risk in mortality in the unadjusted analysis (prevalence ratio = 1.61, p = 0.02), but when propensity-matched analysis was done, there was no statistically significant difference between the two groups. Concerning bleeding or transfusion, there was no difference in bleeding or rates of transfusion (p= 0.22, p = 0.21). CONCLUSION Liver biopsy at the time of MBS is safe. It adds operative time, but there is no increase in length of stay, bleeding complications, morbidity, or death.
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Affiliation(s)
- Benjamin Clapp
- Department of Surgery, Texas Tech Health Sciences Center Paul Foster School of Medicine, 1700 N. Mesa, El Paso, TX, 79902, USA.
| | - Christopher Dodoo
- Department of Surgery, Texas Tech Health Sciences Center Paul Foster School of Medicine, 1700 N. Mesa, El Paso, TX, 79902, USA
| | - Jisoo Kim
- Department of Surgery, Texas Tech Health Sciences Center Paul Foster School of Medicine, 1700 N. Mesa, El Paso, TX, 79902, USA
| | - Christian Castro
- Department of Surgery, Texas Tech Health Sciences Center Paul Foster School of Medicine, 1700 N. Mesa, El Paso, TX, 79902, USA
| | - Ellen Wicker
- Department of Surgery, Texas Tech Health Sciences Center Paul Foster School of Medicine, 1700 N. Mesa, El Paso, TX, 79902, USA
| | - Roshni Mandania
- Department of Surgery, Texas Tech Health Sciences Center Paul Foster School of Medicine, 1700 N. Mesa, El Paso, TX, 79902, USA
| | - Brian Davis
- Department of Surgery, Texas Tech Health Sciences Center Paul Foster School of Medicine, 1700 N. Mesa, El Paso, TX, 79902, USA
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El Kassas M, Alboraie M, El-Sayed M, Elbehiry S, Sherief A, Youssef M, Moaz I, El Tahan A, Abdeen N, Eysa B, Aziz AA, Tawheed A, Ezzat S, Hassany M. Effect of disease stage and treatment outcomes on the dynamics of liver functions during and after treatment of hepatitis C with directly acting antivirals. Eur J Gastroenterol Hepatol 2021; 33:e302-e307. [PMID: 34080825 DOI: 10.1097/meg.0000000000002043] [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] [Indexed: 12/10/2022]
Abstract
BACKGROUND Virus C infection is recently treated successfully with plenty of direct antiviral agents (DAAs). We aimed to evaluate the effect of disease stage and treatment outcome on the dynamics of liver functions during treatment of hepatitis C with DAAs. METHODS We reported the liver function in 2354 subjects diagnosed as chronic hepatitis C before, during and after treatment with different DAAs regimens. Patients were classified into two groups according to treatment response with further subclassification according to the presence or absence of cirrhosis, and changes in liver functions were compared in each group and subgroup. RESULTS Totally 2213 (94%) achieved sustained virological response (SVR) to DAAs therapy with significant improvement in all liver biochemistry. Also, there was an improvement in the non-SVR group's liver enzymes in relapsers during and after treatment; however, there was no improvement in serum albumin. We noticed a slight increase in serum bilirubin at weeks 4 and 8 for both groups. CONCLUSION DAAs therapy is associated with improvement of the liver biochemical profile and improved outcome in the majority of chronic hepatitis C virus patients due to suppression of viral replication. However, the long-term impact of DAAs therapy needs to be further evaluated.
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Affiliation(s)
| | | | | | | | - Ahmed Sherief
- Tropical Medicine Department, Faculty of Medicine Ain Shams University, Cairo
| | | | - Inas Moaz
- Epidemiology and Preventive Medicine Department, National Liver Institute, Menoufia University, Menoufia
| | - Adel El Tahan
- New Cairo Viral Hepatitis, Treatment Unit, New Cairo Hospital, Cairo
| | - Nermeen Abdeen
- Tropical Medicine, Faculty of Medicine, Alexandria University, Alexandria
| | - Basem Eysa
- Tropical Medicine Department, National Hepatology and Tropical Medicine Research Institute
| | - Ayman A Aziz
- Gastroenterology and Hepatology Department, Theodor Bilharz Research Institute, Cairo, Egypt
| | - Ahmed Tawheed
- Endemic Medicine Department, Faculty of Medicine, Helwan University
| | - Sameera Ezzat
- Epidemiology and Preventive Medicine Department, National Liver Institute, Menoufia University, Menoufia
| | - Mohamed Hassany
- Tropical Medicine Department, National Hepatology and Tropical Medicine Research Institute
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Kim J, Han K, Yoo J, Park KA, Oh SY. Liver enzymes and risk of ocular motor cranial nerve palsy: a nationwide population-based study. Neurol Sci 2021; 43:3395-3405. [PMID: 34811598 DOI: 10.1007/s10072-021-05735-9] [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: 06/18/2021] [Accepted: 11/03/2021] [Indexed: 01/09/2023]
Abstract
This study aimed to assess the associations between liver enzymes including γ-glutamyl transferase (GGT) and the development of ocular motor cranial nerve palsy (CNP) using the National Sample Cohort database from Korea's National Health Insurance Service. We analyzed data from 4,233,273 medical screening examinees aged 20 years or more in 2009. Study participants were followed up until December 31, 2018. A Cox proportional hazard regression analysis was performed for quartiles of liver enzymes to determine the linkage between each value and ocular motor CNP using quartile 1 as a reference after adjusting for potential confounders. A total of 5,807 (0.14%) patients developed ocular motor CNP during the follow-up period of 8.22 ± 0.94 years. The incidence of ocular motor CNP gradually increased as the GGT levels increased. The highest quartile of the GGT group had hazard ratio (HR) of 1.245 (95% confidence interval [CI], 1.136-1.365). Regarding alanine aminotransferase (ALT), the highest quartile of the ALT group had HR of 1.141 (95% CI, 1.049-1.241). However, the incidence of ocular motor CNP did not gradually increase as the ALT levels increased. The coexistence of the increased level of GGT, metabolic syndrome, and obesity showed a stronger association with ocular motor CNP development (HR, 1.331; 95% CI, 1.173, 1.511) compared to having a single factor or two factors. In conclusion, our population-based cohort study demonstrated a significant association between serum GGT level and the incidence of ocular motor CNP, suggesting that GGT could be a new clinical marker for predicting the occurrence of ocular motor CNP.
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Affiliation(s)
- Joonhyoung Kim
- Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kyungdo Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, Republic of Korea.
| | - Juhwan Yoo
- Department of Biomedicine and Health Science, The Catholic University of Korea, Seoul, Republic of Korea
| | - Kyung-Ah Park
- Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
| | - Sei Yeul Oh
- Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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Spitler KM, Shetty SK, Cushing EM, Sylvers-Davie KL, Davies BSJ. Chronic high-fat feeding and prolonged fasting in liver-specific ANGPTL4 knockout mice. Am J Physiol Endocrinol Metab 2021; 321:E464-E478. [PMID: 34396783 PMCID: PMC8560380 DOI: 10.1152/ajpendo.00144.2021] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Obesity is associated with dyslipidemia, ectopic lipid deposition, and insulin resistance. In mice, the global or adipose-specific loss of function of the protein angiopoietin-like 4 (ANGPTL4) leads to decreased plasma triglyceride levels, enhanced adipose triglyceride uptake, and protection from high-fat diet (HFD)-induced glucose intolerance. ANGPTL4 is also expressed highly in the liver, but the role of liver-derived ANGPTL4 is unclear. The goal of this study was to determine the contribution of hepatocyte ANGPTL4 to triglyceride and glucose homeostasis in mice during a high-fat diet challenge. We generated hepatocyte-specific ANGPTL4 deficient (Angptl4LivKO) mice, fed them a 60% kcal/fat diet (HFD) for 6 mo and assessed triglyceride, liver, and glucose metabolic phenotypes. We also explored the effects of prolonged fasting on Angptl4LivKO mice. The loss of hepatocyte-derived ANGPTL4 led to no major changes in triglyceride partitioning or lipoprotein lipase activity compared with control mice. Interestingly, although there was no difference in fasting plasma triglyceride levels after a 6 h fast, after an 18-h fast, normal chow diet-fed Angptl4LivKO mice had lower triglyceride levels than control mice. On a HFD, Angptl4LivKO mice initially showed no difference in glucose tolerance and insulin sensitivity, but improved glucose tolerance emerged in these mice after 6 mo on HFD. Our data suggest that hepatocyte ANGPTL4 does not directly regulate triglyceride partitioning, but that loss of liver-derived ANGPTL4 may be protective from HFD-induced glucose intolerance and influence plasma triglyceride (TG) metabolism during prolonged fasting.NEW & NOTEWORTHY1) Angiopoietin-like 4 deficiency in hepatocytes (Angptl4LivKO) does not improve triglyceride phenotypes during high-fat feeding. 2) Angptl4LivKO mice have improved glucose tolerance after chronic high-fat diet. 3) Angptl4LivKO mice have decreased fasting plasma triglyceride levels after an 18-h fast, but not after a 6-h fast.
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Affiliation(s)
- Kathryn M Spitler
- Department of Biochemistry, Fraternal Order of Eagles Diabetes Research Center, and Obesity Research and Education Initiative, University of Iowa, Iowa City, Iowa
| | - Shwetha K Shetty
- Department of Biochemistry, Fraternal Order of Eagles Diabetes Research Center, and Obesity Research and Education Initiative, University of Iowa, Iowa City, Iowa
| | - Emily M Cushing
- Department of Biochemistry, Fraternal Order of Eagles Diabetes Research Center, and Obesity Research and Education Initiative, University of Iowa, Iowa City, Iowa
| | - Kelli L Sylvers-Davie
- Department of Biochemistry, Fraternal Order of Eagles Diabetes Research Center, and Obesity Research and Education Initiative, University of Iowa, Iowa City, Iowa
| | - Brandon S J Davies
- Department of Biochemistry, Fraternal Order of Eagles Diabetes Research Center, and Obesity Research and Education Initiative, University of Iowa, Iowa City, Iowa
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Wang H, Li L, Zhang S. Non-linear relationship between gamma-glutamyl transferase and type 2 diabetes mellitus risk: secondary analysis of a prospective cohort study. J Int Med Res 2021; 48:300060520937911. [PMID: 32662704 PMCID: PMC7361500 DOI: 10.1177/0300060520937911] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
OBJECTIVE To investigate the association between gamma-glutamyl transferase (GGT) and type 2 diabetes mellitus (T2DM) risk. METHODS This was a secondary analysis based on a publicly available DRYAD dataset that included 15 444 study participants that received medical examinations at a single centre in Japan between 2004 and 2015. Crude, minimally-adjusted and fully-adjusted regression models were used to evaluate the relationship between GGT levels and T2DM risk. RESULTS The study participants (mean ± SD age of 43.72 ± 8.90 years; 8415 of 15 444 [54.49%] were male) were followed-up for a median of 1968 days (5.39 years). After adjusting for potential covariates, a non-linear relationship between the baseline GGT level and T2DM incidence was observed. The inflection point for T2DM risk was 10 IU/l GGT; below this point, the T2DM incidence increased by 1.18-fold per unit change in GGT. Above this point, the association between GGT and the incidence rate of T2DM became nonsignificant. CONCLUSION Baseline GGT exhibited a non-linear association with T2DM incidence. Elevated GGT levels should be incorporated into routine screening for individuals at high risk of T2DM, allowing for early intervention targeting GGT to potentially reduce T2DM-related morbidity.
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Affiliation(s)
- Hao Wang
- Department of Cardiology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, Henan Province, China
| | - Lixia Li
- Department of Cardiology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, Henan Province, China
| | - Shouyan Zhang
- Department of Cardiology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, Henan Province, China
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Ali N, Sumon AH, Fariha KA, Asaduzzaman M, Kathak RR, Molla NH, Mou AD, Barman Z, Hasan M, Miah R, Islam F. Assessment of the relationship of serum liver enzymes activity with general and abdominal obesity in an urban Bangladeshi population. Sci Rep 2021; 11:6640. [PMID: 33758311 PMCID: PMC7988042 DOI: 10.1038/s41598-021-86216-z] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Accepted: 03/12/2021] [Indexed: 12/13/2022] Open
Abstract
Obesity is a global health concern because of its increasing trend both in developed and developing countries. A limited number of studies have evaluated the association of liver enzymes with both general and abdominal obesity in the general population; data for the Bangladeshi population are not available yet. This study aimed to assess the relationship of serum liver enzymes activity with both general and abdominal obesity in Bangladeshi adults. In total, 540 blood samples were obtained from the participants (388 males and 152 females) and analyzed for serum levels of ALT, AST, GGT, and ALP using standard methods. General obesity was defined as body mass index (BMI) ≥ 27.5 kg/m2 and abdominal obesity was defined as waist circumference (WC) ≥ 90 cm in males and ≥ 80 cm in females. The relationship between liver enzymes and obesity was evaluated by multivariate logistic regression models. Overall, 58% of participants in the general obesity group and 55% of the participants in the abdominal obesity group had at least one or more elevated levels of liver enzymes. The prevalence of elevated liver enzymes was significantly higher in the obesity group compared to the normal BMI and WC groups (p < 0.05 for all cases). The mean level of serum ALT, AST and GGT were significantly higher in the obesity group than the normal BMI group (p < 0.05). In the WC groups, mean AST and GGT were significantly higher in the obesity group compared to the normal group (p < 0.05). In regression analysis, serum levels of ALT showed an independent and significant association with general obesity, whereas, serum GGT showed a significant association with both general and abdominal obesity. In conclusion, a high prevalence of elevated liver enzymes was observed among participants included in the present study. Of the four enzymes, serum GGT was independently associated with both general and abdominal obesity. Further studies are required to understand the complex relationship between liver enzymes and obesity in the general population.
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Affiliation(s)
- Nurshad Ali
- Department of Biochemistry and Molecular Biology, Shahjalal University of Science and Technology, Sylhet, 3114, Bangladesh.
| | - Abu Hasan Sumon
- Department of Biochemistry and Molecular Biology, Shahjalal University of Science and Technology, Sylhet, 3114, Bangladesh
| | - Khandaker Atkia Fariha
- Department of Biochemistry and Molecular Biology, Shahjalal University of Science and Technology, Sylhet, 3114, Bangladesh
| | - Md Asaduzzaman
- Department of Biochemistry and Molecular Biology, Shahjalal University of Science and Technology, Sylhet, 3114, Bangladesh
| | - Rahanuma Raihanu Kathak
- Department of Biochemistry and Molecular Biology, Shahjalal University of Science and Technology, Sylhet, 3114, Bangladesh
| | - Noyan Hossain Molla
- Department of Biochemistry and Molecular Biology, Shahjalal University of Science and Technology, Sylhet, 3114, Bangladesh
| | - Ananya Dutta Mou
- Department of Biochemistry and Molecular Biology, Shahjalal University of Science and Technology, Sylhet, 3114, Bangladesh
| | - Zitu Barman
- Department of Biochemistry and Molecular Biology, Shahjalal University of Science and Technology, Sylhet, 3114, Bangladesh
| | - Mahmudul Hasan
- Department of Biochemistry and Molecular Biology, Shahjalal University of Science and Technology, Sylhet, 3114, Bangladesh
| | - Rakib Miah
- Department of Biochemistry and Molecular Biology, Shahjalal University of Science and Technology, Sylhet, 3114, Bangladesh
| | - Farjana Islam
- Department of Biochemistry and Molecular Biology, Shahjalal University of Science and Technology, Sylhet, 3114, Bangladesh
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22
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Andreacchi AT, Griffith LE, Guindon GE, Mayhew A, Bassim C, Pigeyre M, Stranges S, Anderson LN. Body mass index, waist circumference, waist-to-hip ratio, and body fat in relation to health care use in the Canadian Longitudinal Study on Aging. Int J Obes (Lond) 2021; 45:666-676. [PMID: 33432110 DOI: 10.1038/s41366-020-00731-z] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Revised: 10/21/2020] [Accepted: 12/09/2020] [Indexed: 01/29/2023]
Abstract
BACKGROUND/OBJECTIVES Obesity is associated with increased health care use (HCU), but it is unclear whether this is consistent across all measures of adiposity. The objectives were to compare obesity defined by body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and percent body fat (%BF), and to estimate their associations with HCU. SUBJECTS/METHODS Baseline data from 30,092 participants aged 45-85 years from the Canadian Longitudinal Study on Aging were included. Measures of adiposity were recorded by trained staff and obesity was defined as BMI ≥ 30.0 kg/m2 for all participants and WC ≥ 88 cm and ≥102 cm, WHR ≥ 0.85 and ≥0.90, and %BF > 35% and >25% (measured using dual energy x-ray absorptiometry) for females and males, respectively. Self-reported HCU in the past 12 months was collected for any contact with a general practitioner, specialist, emergency department, and hospitalization. Pearson correlation coefficients (r) compared each measure to %BF-defined obesity, the reference standard. Relative risks (RR) and risk differences (RD) adjusted for age, sex, education, income, urban/rural, marital status, smoking status, and alcohol use were calculated, and results were age- and sex-stratified. RESULTS Obesity prevalence varied by measure: BMI (29%), WC (42%), WHR (62%), and %BF (73%). BMI and WC were highly correlated with %BF (r ≥ 0.70), while WHR demonstrated a weaker relationship with %BF, with differences by sex (r = 0.29 and r = 0.46 in females and males, respectively). There were significantly increased RR and RD for all measures and health care services, for example, WC-defined obesity was associated with an increased risk of hospitalization (RR: 1.40, 95% CI: 1.28-1.54 and RD per 100: 2.6, 95% CI:1.9-3.3). Age-stratified results revealed that older adult groups with obesity demonstrated weak or no associations with HCU. CONCLUSIONS All measures of adiposity were positively associated with increased HCU although obesity may not be a strong predictor of HCU in older adults.
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Affiliation(s)
- Alessandra T Andreacchi
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada
| | - Lauren E Griffith
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada
| | - G Emmanuel Guindon
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.,Centre for Health Economics and Policy Analysis, McMaster University, Hamilton, Ontario, Canada
| | - Alexandra Mayhew
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada
| | - Carol Bassim
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada
| | - Marie Pigeyre
- Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton, Ontario, Canada.,Department of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Saverio Stranges
- Department of Epidemiology and Biostatistics, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada.,Department of Population Health, Luxembourg Institute of Health, Strassen, Luxembourg.,Department of Family Medicine, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada
| | - Laura N Anderson
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada. .,Centre for Health Economics and Policy Analysis, McMaster University, Hamilton, Ontario, Canada. .,Division of Child Health Evaluative Sciences (CHES), Sick Kids Research Institute, Toronto, Ontario, Canada.
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23
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Lee YJ, Han KD, Kim DH, Lee CH. Determining the association between repeatedly elevated serum gamma-glutamyltransferase levels and risk of respiratory cancer: A nationwide population-based cohort study. Cancer Med 2021; 10:1366-1376. [PMID: 33638317 PMCID: PMC7925999 DOI: 10.1002/cam4.3735] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Revised: 12/15/2020] [Accepted: 12/16/2020] [Indexed: 11/05/2022] Open
Abstract
Background Although elevated serum gamma‐glutamyltransferase (GGT) is a known indicator of increased risk of several cancers, the clinical value of repeated measurements of GGT has not been determined. Therefore, we aimed to investigate whether repeatedly elevated serum GGT levels are associated with the risk of respiratory cancer incidence. Methods We included participants who had undergone the Korean Health screening four times during 2009–2012 and had previously undergone four consecutive examinations. Those who were diagnosed with respiratory cancer before the date of examination were excluded. The participants obtained one GGT point if their GGT levels were in the highest quartile (the quartile 4 group). We analyzed the association between GGT points and respiratory cancer incidence by Cox proportional hazard models. Results During mean follow‐up of 6.39 ± 1.2 years, 3,559,109 participants were enrolled. Of them, 8,944 (0.34%) men and 1,484 (0.14%) women were newly diagnosed with respiratory cancer. In multivariate analysis adjusted for confounding factors, male participants with 4 GGT points had a significantly higher hazards of developing respiratory cancer than those with 0 GGT points (hazard ratio [HR]: 1.39; 95% confidence interval [CI]: 1.31–1.48). Among female, participants with the highest points of GGT also had sixfold increased risk of developing laryngeal cancer. However, no significant association was observed between GGT points and lung cancer incidence among women (HR: 0.95; 95% CI: 0.81–1.11). Conclusion Repeatedly elevated serum levels of GGT were associated with a higher risk of respiratory cancer incidence, especially in men. This finding suggests that physicians can identify a person with a higher risk of respiratory cancer through a simple repeated measurement of GGT.
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Affiliation(s)
- Ye Jin Lee
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Kang Dong Sacred Heart Hospital, Seoul, Republic of Korea
| | - Kyung-Do Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, Republic of Korea
| | - Da Hye Kim
- Department of Biostatistics, College of Medicine, Catholic University of Korea, Seoul, Republic of Korea
| | - Chang-Hoon Lee
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea
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Dalla Zuanna T, Savitz DA, Barbieri G, Pitter G, Zare Jeddi M, Daprà F, Fabricio ASC, Russo F, Fletcher T, Canova C. The association between perfluoroalkyl substances and lipid profile in exposed pregnant women in the Veneto region, Italy. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2021; 209:111805. [PMID: 33360787 DOI: 10.1016/j.ecoenv.2020.111805] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Revised: 11/30/2020] [Accepted: 12/10/2020] [Indexed: 05/27/2023]
Abstract
BACKGROUND Residents of a large area of North-Eastern Italy were exposed for decades to high concentrations of perfluoroalkyl and polyfluoroalkyl substances (PFAS) via drinking water. Serum PFAS levels have been consistently associated with elevated serum lipids, but few studies have been conducted among pregnant women, and none has stratified analyses by trimester of gestation. Elevated serum lipid levels during pregnancy can have both immediate and long-lasting effects on pregnant women and the developing fetus. We evaluated the association between perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and perfluoro-hexanesulfonate (PFHxS) levels in relation to lipid profiles in highly-exposed pregnant women. METHODS A cross-sectional analysis was conducted in 319 pregnant women (age 14-48 years) enrolled in the Regional health surveillance program. Non-fasting blood samples were obtained in any trimester of pregnancy and analyzed for PFOA, PFOS and PFHxS, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C). Low-density lipoprotein cholesterol (LDL-C) was calculated. The associations between ln-transformed PFAS (and categorized into quartiles) and lipids were assessed using generalized additive models. Analyses were adjusted for potential confounders and stratified according to pregnancy trimester. RESULTS The geometric means of PFOA, PFOS and PFHxS were 14.78 ng/mL, 2.67 ng/mL and 1.89 ng/mL, respectively. The plasma levels of TC, HDL-C and LDL-C increased steadily throughout the trimesters. In the 1st trimester, PFOS was positively associated with TC and PFHxS with HDL-C. In the 3rd trimester, instead, an inverse relationship was seen between PFOA and PFHxS and both TC and LDL-C. CONCLUSIONS Results suggest the associations between PFAS concentrations and lipid profiles in pregnant women might differ by trimesters of pregnancy. In the first trimester, patterns are similar to those of non-pregnant women, while they differ late in pregnancy. Different independent behavior of PFAS and lipid levels throughout the pregnancy might explain our observations. These findings support the ubiquitous exposure to PFAS and possible influence on lipid metabolisms during pregnancy and suggest a careful evaluation of the timing of PFAS measurement, when examining effects of PFAS during pregnancy on gestational outcomes related to serum lipids amounts.
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Affiliation(s)
- Teresa Dalla Zuanna
- Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, Università di Padova, Via Loredan 18, 35131 Padova, Italy.
| | - David A Savitz
- Department of Epidemiology, Brown University School of Public Health, Providence, RI, United States.
| | - Giulia Barbieri
- Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, Università di Padova, Via Loredan 18, 35131 Padova, Italy
| | - Gisella Pitter
- Screening and Health Impact Assessment Unit, Azienda Zero-Veneto Region, Passaggio L. Gaudenzio 1, 35100 Padova, Italy.
| | - Maryam Zare Jeddi
- Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, Università di Padova, Via Loredan 18, 35131 Padova, Italy
| | - Francesca Daprà
- Laboratory Department-Regional Agency for Environmental Prevention and Protection, Veneto Region, Verona, Italy.
| | - Aline S C Fabricio
- Regional Center for Biomarkers, Department of Clinical Pathology, Azienda ULSS 3 Serenissima, Venice, Italy.
| | - Francesca Russo
- Directorate of Prevention, Food Safety, and Veterinary Public Health, Veneto Region, Dorsoduro, 3493 - Rio Nuovo, 30123 Venice, Italy.
| | - Tony Fletcher
- London School of Hygiene and Tropical Medicine, London, United Kingdom.
| | - Cristina Canova
- Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, Università di Padova, Via Loredan 18, 35131 Padova, Italy.
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Association of Metabolically Healthy and Unhealthy Obesity Phenotypes with Oxidative Stress Parameters and Telomere Length in Healthy Young Adult Men. Analysis of the MAGNETIC Study. Antioxidants (Basel) 2021; 10:antiox10010093. [PMID: 33440881 PMCID: PMC7826733 DOI: 10.3390/antiox10010093] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2020] [Revised: 12/29/2020] [Accepted: 01/06/2021] [Indexed: 02/07/2023] Open
Abstract
Obesity is a significant factor related to metabolic disturbances that can lead to metabolic syndrome (MetS). Metabolic dysregulation causes oxidative stress, which affects telomere structure. The current study aimed to evaluate the relationships between telomere length, oxidative stress and the metabolically healthy and unhealthy phenotypes in healthy young men. Ninety-eight participants were included in the study (49 healthy slim and 49 obese patients). Study participants were divided into three subgroups according to body mass index and metabolic health. Selected oxidative stress markers were measured in serum. Relative telomere length (rTL) was measured using quantitative polymerase chain reaction. The analysis showed associations between laboratory markers, oxidative stress markers and rTL in metabolically healthy and unhealthy participants. Total oxidation status (TOS), total antioxidant capacity (TAC) and rTL were significantly connected with metabolically unhealthy obesity. TAC was associated with metabolically healthy obesity. Telomeres shorten in patients with metabolic dysregulation related to oxidative stress and obesity linked to MetS. Further studies among young metabolically healthy and unhealthy individuals are needed to determine the pathways related to metabolic disturbances that cause oxidative stress that leads to MetS.
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26
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Laine S, Sjöros T, Vähä-Ypyä H, Garthwaite T, Löyttyniemi E, Sievänen H, Vasankari T, Knuuti J, Heinonen IHA. Body Adiposity, But Not Elements of Objectively Measured Sedentary Behavior or Physical Activity, Is Associated With Circulating Liver Enzymes in Adults With Overweight and Obesity. Front Endocrinol (Lausanne) 2021; 12:655756. [PMID: 33959099 PMCID: PMC8095079 DOI: 10.3389/fendo.2021.655756] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Accepted: 03/29/2021] [Indexed: 01/04/2023] Open
Abstract
OBJECTIVE We studied the associations between accelerometer-measured sedentary behavior (SB) and habitual physical activity (PA) as well as markers of body adiposity and other cardiometabolic risk factors with liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyltransferase (GGT). METHODS A total of 144 middle-aged adults (mean age 57 (SD 6.5) years) with overweight or obesity (mean body mass index [BMI] 31.8 [SD 3.9] kg/m2) participated. Different components of SB (sitting, lying) and PA (standing, breaks in SB, daily steps, light PA, moderate-to-vigorous PA and total PA) were measured with validated hip-worn accelerometers for four consecutive weeks (mean 25 days, [SD 4]). Fasting venous blood samples were analysed using standard assays. The associations were examined with Pearson's partial correlation coefficient test and linear mixed model. RESULTS Among 102 women and 42 men accelerometer measured SB or the elements of PA were not associated with circulating liver enzymes. When adjusted for age and sex, liver enzymes correlated positively with BMI and waist circumference (WC) (ALT r=0.34, p<0.0001, r=0.41, < 0.0001, AST r=0.17, p=0.049, r=0.26, p=0.002, GGT r=0.29, p=0.0005, r=0.32, p < 0.0001, respectively). SB proportion associated positively with BMI (r=0.21, p=0.008) and WC (r=0.27, p=0.001). Components of PA associated negatively with BMI (MVPA r=-0.23, p=0.005, daily steps r=-0.30, p<0.0001 and breaks in sedentary time r=-0.32, p<0.0001), as well as with WC (breaks in SB r=-0.35, p<0.0001, MVPA r=-0.26, p=0.002, daily steps r=-0.31, p<0.0001, standing time r=-0.27, p=0.001). Liver enzymes associated positively with common cardiometabolic markers such as resting heart rate (ALT; β=0.17, p=0.03, AST; β=0.25, p=0.002, GGT; β=0.23, p=0.004) and systolic/diastolic blood pressure (ALT β=0.20, p=0.01, β=0.22, p=0.005, AST (only diastolic) β=0.23, p=0.006, GGT β=0.19, p=0.02, = 0.23, p=0.004, respectively), fasting insulin (ALT β=0.41, p<0.0001, AST β=0.36, p=0.0003, GGT β=0.20, p=0.04) and insulin resistance index (ALT β=0.42, p<0.0001, AST β=0.36, p=0.0003, GGT β=0.21, p=0.03), even after adjustment with BMI. CONCLUSIONS Liver enzymes correlate with body adiposity and appear to cluster with other common cardiometabolic risk factors, even independently of body adiposity. SB and PA appear not to be essential in modulating the levels of circulating liver enzymes.
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Affiliation(s)
- Saara Laine
- Turku PET Centre, University of Turku and Turku University Hospital, Turku, Finland
- *Correspondence: Saara Laine,
| | - Tanja Sjöros
- Turku PET Centre, University of Turku and Turku University Hospital, Turku, Finland
| | - Henri Vähä-Ypyä
- The UKK-Institute for Health Promotion Research, Tampere, Finland
| | - Taru Garthwaite
- Turku PET Centre, University of Turku and Turku University Hospital, Turku, Finland
| | | | - Harri Sievänen
- The UKK-Institute for Health Promotion Research, Tampere, Finland
| | - Tommi Vasankari
- The UKK-Institute for Health Promotion Research, Tampere, Finland
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Juhani Knuuti
- Turku PET Centre, University of Turku and Turku University Hospital, Turku, Finland
| | - Ilkka H. A. Heinonen
- Turku PET Centre, University of Turku and Turku University Hospital, Turku, Finland
- Rydberg Laboratory of Applied Sciences, University of Halmstad, Halmstad, Sweden
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Zaki M, Amin D, Mohamed R. Body composition, phenotype and central obesity indices in Egyptian women with non-alcoholic fatty liver disease. JOURNAL OF COMPLEMENTARY & INTEGRATIVE MEDICINE 2020; 18:385-390. [PMID: 34187121 DOI: 10.1515/jcim-2020-0073] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/22/2020] [Accepted: 06/12/2020] [Indexed: 12/12/2022]
Abstract
OBJECTIVES Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. The aim of this study is to investigate body composition and phenotype of Egyptian women with non-alcoholic fatty liver disease (NAFLD) and compare with those without and determine the optimal cut-off values of central obesity indices for predicting NAFLD. METHODS The study included 100 women with NAFLD and 100 age and sex matched healthy controls without NAFLD. All women were subjected to ultrasonography examination. Anthropometric measurements included weight, height, waist circumference (WC), hip circumference (HC) and skinfolds thickness were assessed for all participants. Body fat % was evaluated by Tanita body composition analyzer. Body mass index (BMI), WC / height ratio (WHtR), WC / HC ratio (WHR) and visceral adiposity index (VAI) were calculated. Receiver-operating characteristic (ROC) curve was used to determine the optimal cut-off values. RESULTS Data showed significant higher levels of WHtR, WHR, BMI, sum of skinfolds, body fat %, serum fasting blood lipids and glucose in NAFLD women compared to group of patients without NAFLD. The area under curve (AUC) was 0.920 for VIA, 0.883 for WHtR and 0.647 for WHR. The optimal cutoff value of VAI was 3.66, of WHtR was 0.66 and WHR was 0.84. All values showed high sensitivity and specificity values. CONCLUSION NAFLD women were obese, had excess subcutaneous fat and body fat ratio. Central obesity indices are closely associated with the presence of NAFLD in Egyptian women and might be responsible for its development. Visceral adiposity index had superior diagnostic performance.
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Affiliation(s)
- Moushira Zaki
- Biological Anthropology Department, Medical Research Division, National Research Centre, Cairo, Egypt
| | - Darine Amin
- Biological Anthropology Department, Medical Research Division, National Research Centre, Cairo, Egypt
| | - Ramy Mohamed
- Biological Anthropology Department, Medical Research Division, National Research Centre, Cairo, Egypt
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Fermented Rhus Verniciflua Stokes Extract Alleviates Nonalcoholic Fatty Liver through the AMPK/SREBP1/PCSK9 Pathway in HFD-Induced Nonalcoholic Fatty Liver Animal Model. APPLIED SCIENCES-BASEL 2020. [DOI: 10.3390/app10196833] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Background: We have previously reported the anti-hepatic lipogenic effect of fermented Rhus verniciflua stokes extract (FRVE) in an oleic-acid-treated HepG2 cell model. Methods: Herein, we advanced our understanding and evaluated the impact of FRVE in HFD-fed C57BL/6 mice using an animal model of nonalcoholic fatty liver disease (NAFLD). Milk thistle extract was used as a positive control to compare the effects of FRVE. Results: FRVE decreased body weight, intra-abdominal fat weight, and liver weight. Furthermore, FRVE decreased HFD-induced elevated serum levels of ALT, AST, TC, and TG, and downregulated the increase in hepatic lipid accumulation and TG levels. FRVE reduced hepatic SREBP-1, PCSK-9, SREBP-2, and ApoB mRNA levels. IHC data showed that FRVE reduced the levels of nucleic SREBP-1, increased the levels of LDLR, and upregulated the expression of p-AMPK. Conclusion: Overall, these results demonstrate the anti-hepatic lipidemic effect of FRVE in an animal model. These findings are consistent with our previous study and strongly suggest that FRVE exerts anti-hepatic lipogenic effects by activating AMPK.
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Lee DY, Han K, Yu JH, Park S, Seo JA, Kim NH, Yoo HJ, Kim SG, Kim SM, Choi KM, Baik SH, Park YG, Kim NH. Prognostic value of long-term gamma-glutamyl transferase variability in individuals with diabetes: a nationwide population-based study. Sci Rep 2020; 10:15375. [PMID: 32958798 PMCID: PMC7506020 DOI: 10.1038/s41598-020-72318-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2020] [Accepted: 08/19/2020] [Indexed: 11/09/2022] Open
Abstract
We examined whether long-term gamma-glutamyl transferase (GGT) variability can predict cardiovascular disease (CVD) and mortality in individuals with diabetes. We included 698,937 Koreans diabetes patients older than 40 years without histories of CVD, chronic liver disease, or heavy alcoholics who received health exams supported by the Korean government more than once in 2009-2012 (baseline). We used Cox proportional analyses to estimate the risk of stroke, myocardial infarction (MI), and all-cause mortality until December 31, 2016, according to the quartiles of the average successive variability (ASV) of GGT measured during the five years before the baseline. A total 26,119, 15,103, and 39,982 cases of stroke, MI, and death, respectively, were found. GGT ASV quartile 4 had a significantly higher risk of stroke and all-cause mortality than quartile 1, with adjustment for risk factors, such as baseline glucose and GGT level, and comorbidities. Hazard ratios (95% confidence intervals) for GGT ASV quartile 4 were 1.06 (1.03-1.10) and 1.23 (1.20-1.27) for stroke and mortality, respectively. This significant association was shown consistently across the baseline GGT quartiles. GGT variability was related to the risk of stroke and all-cause mortality. The effect was most pronounced in all-cause mortality, irrespective of baseline GGT level.
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Affiliation(s)
- Da Young Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Kyungdo Han
- Department of Biostatics, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea
| | - Ji Hee Yu
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Sanghyun Park
- Department of Biostatics, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea
| | - Ji A Seo
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Nam Hoon Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Hye Jin Yoo
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Sin Gon Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Seon Mee Kim
- Department of Family Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Kyung Mook Choi
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Sei Hyun Baik
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Yong Gyu Park
- Department of Biostatics, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.
| | - Nan Hee Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea.
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Differences among patients with and without nonalcoholic fatty liver disease having elevated alanine aminotransferase levels at various stages of metabolic syndrome. PLoS One 2020; 15:e0238388. [PMID: 32866186 PMCID: PMC7458345 DOI: 10.1371/journal.pone.0238388] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Accepted: 08/14/2020] [Indexed: 12/20/2022] Open
Abstract
Background The prevalence of nonalcoholic fatty liver disease (NAFLD) in the non-obese population has increased and NAFLD is not always recognized in individuals with metabolic syndrome (MS). The risk of cirrhosis is higher in patients having NAFLD with elevated alanine aminotransferase (ALT) levels than in those having NAFLD with normal ALT levels. Objective To measure the differences in clinical factors associated with NAFLD having elevation of ALT among subjects with Non-MS, Pre-MS, and MS, and to measure differences in metabolites between MS subjects with and without NAFLD having elevation of ALT. Methods Among 7,054 persons undergoing health check-ups, we included 3,025 subjects who met the selection criteria. We measured differences in clinical factors for NAFLD having elevation of ALT among subjects with Non-MS, Pre-MS, and MS, and compared metabolites between subjects with and without NAFLD having elevation of ALT in 32 subjects with MS. Results The prevalence of NAFLD and NAFLD having elevation of ALT was significantly progressively greater in subjects with Non-MS, Pre-MS, and MS (p <0.001, respectively). In the Non-MS group, there were significant differences between subjects with and without NAFLD having elevation of ALT with respect to body mass index (BMI), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, hemoglobin A1c, uric acid, aspartate aminotransferase (AST); In the Pre-MS group, there were significant differences in BMI, hypertension, AST, and gamma-glutamyl transpeptidase (GGT); In the MS group, there were significant differences in HDL-C, impaired glucose tolerance, AST, and GGT. There were significant differences in levels of metabolites of nicotinamide, inosine, and acetyl-L-carnitine between MS subjects with and without NAFLD having elevation of ALT (all p <0.05). Conclusions Although NAFLD having elevation of ALT is important for development of NAFLD, differences in factors associated with NAFLD having elevation of ALT at various stages of MS should be considered. Additionally, several metabolites may play roles in the identification of risk for NAFLD in individuals with MS.
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Dorling JL, Ravussin E, Redman LM, Bhapkar M, Huffman KM, Racette SB, Das SK, Apolzan JW, Kraus WE, Höchsmann C, Martin CK. Effect of 2 years of calorie restriction on liver biomarkers: results from the CALERIE phase 2 randomized controlled trial. Eur J Nutr 2020; 60:1633-1643. [PMID: 32803412 DOI: 10.1007/s00394-020-02361-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Accepted: 08/05/2020] [Indexed: 12/18/2022]
Abstract
PURPOSE Calorie restriction (CR) is an effective treatment for obesity-related liver and metabolic disease. However, CR studies in individuals without obesity are needed to see if CR could delay disease onset. Liver biomarkers indicate hepatic health and are linked to cardiometabolic disease. Our aim was to examine the effects of a 2-year CR intervention on liver biomarkers in healthy individuals without obesity. METHODS The Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) study was a 2-year randomized controlled trial. Overall, 218 participants (body mass index: 25.1 ± 1.7 kg/m2) were enrolled into a control group (n = 75) that ate ad libitum (AL), or a CR group (n = 143) that aimed to decrease energy intake by 25%. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and bilirubin were measured during the trial. RESULTS At month 24, relative to the AL group, ALP (- 7 ± 1 IU/L; P < 0.01) and GGT (- 0.11 ± 0.04 log IU/L; P = 0.02) decreased and bilirubin increased (0.21 ± 0.06 log mg/dL; P < 0.01) in the CR group; no between-group differences in ALT (- 1 ± 1 IU/L; P > 0.99) or AST (2 ± 2 IU/L; P = 0.68) were revealed. However, sex-by-treatment-by-time interactions (P < 0.01) were observed, with CR (vs. control) inducing reduced ALT and GGT and increased AST in men only (P ≤ 0.02). CONCLUSIONS In metabolically healthy individuals without obesity, 2 years of CR improves several liver biomarkers, with potentially greater improvements in men. These data suggest that sustained CR may improve long-term liver and metabolic disease risk in healthy adults. TRIAL REGISTRATION Clinicaltrials.gov (NCT00427193). Registered January 2007.
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Affiliation(s)
- James L Dorling
- Pennington Biomedical Research Center, 6400 Perkins Rd., Baton Rouge, LA, 70808, USA.
| | - Eric Ravussin
- Pennington Biomedical Research Center, 6400 Perkins Rd., Baton Rouge, LA, 70808, USA
| | - Leanne M Redman
- Pennington Biomedical Research Center, 6400 Perkins Rd., Baton Rouge, LA, 70808, USA
| | | | | | | | - Sai K Das
- JM, USDA, Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA
| | - John W Apolzan
- Pennington Biomedical Research Center, 6400 Perkins Rd., Baton Rouge, LA, 70808, USA
| | | | - Christoph Höchsmann
- Pennington Biomedical Research Center, 6400 Perkins Rd., Baton Rouge, LA, 70808, USA
| | - Corby K Martin
- Pennington Biomedical Research Center, 6400 Perkins Rd., Baton Rouge, LA, 70808, USA
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Kelishadi R, Hemati Z, Qorbani M, Motlagh ME, Djalalinia S, Ahadi Z, Shafiee G, Mahdavi Gorabi A, Rastad H, Ziaodini H, Daniali SS, Heshmat R. Association of Alanine Aminotransferase With Different Metabolic Phenotypes of Obesity in Children and Adolescents: The CASPIAN-V Study. Front Endocrinol (Lausanne) 2020; 11:358. [PMID: 32849256 PMCID: PMC7426651 DOI: 10.3389/fendo.2020.00358] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2019] [Accepted: 05/07/2020] [Indexed: 01/04/2023] Open
Abstract
Aim: To determine the association of alanine aminotransferase with different metabolic phenotypes of obesity in a nationally- representative sample of Iranian children and adolescents. Methods: This national study was conducted in the framework of the fifth survey of a national surveillance program entitled Childhood and Adolescence Surveillance and Prevention of Adult Non-communicable Disease study. Participants consisted of 4,200 subjects aged 7-18 years, who were recruited by multistage random cluster sampling from 30 provinces in Iran. They were categorized to normal weight and obese groups and in each group those with and without MetS components. Results: Overall, 3,843 of participants completed the survey (response rate: 91.5%). Their mean (SD) age was 12.58 (3.15) years; 52.6% were boys, and 72.7% lived in urban areas. Mean of alanine aminotransferase (ALT) in subjects with abdominal obesity and general obesity was 8.81 (95% CI: 7.99-9.62) (IU/L) and 8.87 (95% CI: 7.28-10.46) (IU/L), respectively. According to the adjusted model, one unit increment in ALT increased odds of being metabolically non-healthy obese (MNHO) by 2% compared to metabolically healthy non-obese (MHNO) [adj.OR (95% CI): 1.02 (1.01-1.04)]. Also, subjects in the third and fourth quartiles of serum ALT had significantly greater odds of being MNHO than those in its first quartile [Q3/Q1: adj. OR (95% CI): 3.85 (1.70-8.71); Q4/Q1: Adj. OR (95% CI): 3.63 (1.51-8.73)]. Conclusion: This large population-based study revealed significant associations between metabolic phenotypes of obesity and ALT level.
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Affiliation(s)
- Roya Kelishadi
- Pediatrics Department, Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Zeinab Hemati
- Pediatrics Department, Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mostafa Qorbani
- Non-communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Shirin Djalalinia
- Development of Research and Technology Center, Deputy of Research and Technology, Ministry of Health and Medical Education, Tehran, Iran
| | - Zeinab Ahadi
- Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Gita Shafiee
- Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Armita Mahdavi Gorabi
- Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Hadith Rastad
- Social Determinants of Health Research Center, Alborz University of Medical Sciences, Karaj, Iran
| | - Hasan Ziaodini
- Bureau of Health and Fitness, Ministry of Education and Training, Tehran, Iran
| | - Seyede Shahrbanoo Daniali
- Pediatrics Department, Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Ramin Heshmat
- Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
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Oh JH, Ahn KM, Chung SJ, Shim JS, Park HW. Usefulness of routine blood test-driven clusters for predicting acute exacerbation in patients with asthma. Respir Med 2020; 170:106042. [PMID: 32843173 DOI: 10.1016/j.rmed.2020.106042] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Revised: 05/18/2020] [Accepted: 05/21/2020] [Indexed: 12/21/2022]
Abstract
AIM Acute exacerbation (AE) is a significant burden in the management of asthma. In this study we aimed to investigate whether routine blood test results predicted AE in asthmatics. METHODS We applied k-means cluster to routine blood test results which included eosinophil counts, total calcium, phosphorus, uric acid (UA), total cholesterol, total protein, albumin, total bilirubin, alkaline phosphatase, aspartate transaminase (AST), alanine transferase (ALT), gamma-glutamyltransferase, blood urea nitrogen, creatinine, and high-sensitive C-reactive protein (hsCRP) obtained from 590 asthmatics. AEs collected over the prospective follow-up of one-year were used to evaluate clinical trajectories of these clusters. RESULTS Three blood clusters were identified. The essential features of each cluster can be characterized as follows: (i) high eosinophil count, UA, total cholesterol, AST, ALT, and hsCRP levels (Cluster 1); (ii) intermediate features (Cluster 2); (iii) low UA, total cholesterol and total bilirubin levels (Cluster 3). Kaplan-Meier analysis confirmed that clusters were strongly predictive of time to the first AE (log-rank P = 0.001). Hazard ratio for each group was as follows: Cluster 2 = 1, Cluster 1 = 2.67 (1 vs. 2, P = 4.68 × 10-4), and Cluster 3 = 1.69 (2 vs. 3, P = 0.021). CONCLUSIONS We defined three blood clusters in asthmatics. These blood clusters are easily identifiable from routine test results and may help clinicians to predict the future risk of AE in asthmatics.
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Affiliation(s)
- Ji Hyun Oh
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan, Republic of Korea
| | - Kyung-Min Ahn
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Soo Jie Chung
- Department of Pulmonology and Allergy, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Republic of Korea
| | - Ji-Su Shim
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Republic of Korea
| | - Heung-Woo Park
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea; Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Republic of Korea.
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Park EO, Bae EJ, Park BH, Chae SW. The Associations between Liver Enzymes and Cardiovascular Risk Factors in Adults with Mild Dyslipidemia. J Clin Med 2020; 9:E1147. [PMID: 32316417 PMCID: PMC7230762 DOI: 10.3390/jcm9041147] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Revised: 04/11/2020] [Accepted: 04/15/2020] [Indexed: 12/30/2022] Open
Abstract
Hypertension and dyslipidemia often occur as comorbidities, with both being strong risk factors for developing cardiovascular diseases (CVD). Abnormal liver function test could reflect a potential CVD risk even in patients with mild dyslipidemia. The aim of this study was to assess the compounding relationship between liver enzymes and cardiovascular risk factors in subjects with mild dyslipidemia. The present analysis was performed among 438 participants who had enrolled in at least one of the nine clinical studies done at the Chonbuk National University Hospital between 2009 and 2019. Significant linear increasing trends were observed in blood pressure level and other cardiovascular risk factors across quartiles of serum γ-glutamyltransferase (GGT) or alanine aminotransferase (ALT), with the increment in hypertension prevalence occurring across the quartiles of GGT and ALT. On multivariate logistic regression analyses, the odds ratios for hypertension, adjusted for smoking, drinking and obesity, in the highest quartiles of GGT, ALT, aspartate aminotransferase, and alkaline phosphatase were 3.688, 1.617, 1.372, and 1.166, respectively. Our study indicates that GGT is a superior marker for predicting CVD risk among liver enzymes. Routine screening of plasma GGT levels in patients with mild dyslipidemia will allow for early detection of CVD.
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Affiliation(s)
- Eun-Ock Park
- Clinical Trial Center for Functional Foods, Chonbuk National University Hospital, Jeonju 54907, Jeonbuk, Korea;
| | - Eun Ju Bae
- College of Pharmacy, Chonbuk National University, Jeonju 54896, Jeonbuk, Korea;
| | - Byung-Hyun Park
- Department of Biochemistry and Molecular Biology, Chonbuk National University Medical School, Jeonju 54896, Jeonbuk, Korea
| | - Soo-Wan Chae
- Clinical Trial Center for Functional Foods, Chonbuk National University Hospital, Jeonju 54907, Jeonbuk, Korea;
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Ding Z, Zhang J, Deng CY, You YB, Zhou H. Association of body mass index with serum alanine aminotransferase in Chinese adolescents: a school-based cross-sectional study. Gastroenterol Rep (Oxf) 2020; 8:119-124. [PMID: 32280471 PMCID: PMC7136703 DOI: 10.1093/gastro/goz039] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2019] [Revised: 07/30/2019] [Accepted: 07/30/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Numerous studies have consistently demonstrated that high body mass index (BMI) is related to elevated serum alanine aminotransferase (ALT) among adults, but little is known about the association regarding adolescents, especially in China. In this study, we aimed to investigate the association between BMI and ALT activity among Chinese adolescents. METHODS A school-based cross-sectional study was performed among nine high schools in Shenzhen, China between February 2017 and June 2018. A generalized linear-regression model adjusting for age and gender was conducted, and bivariate correlation analysis between ALT and BMI was also performed. RESULTS A total of 7,271 adolescents aged from 9 years to 17 years were enrolled. Height, weight, BMI, and ALT were higher among boys than among girls (all P < 0.001). The mean (standard deviation) of serum ALT levels was 14.26 (14.77) U/L. In the entire BMI range, the BMI-ALT correlation was stronger for boys (Spearman's r = 0.396, P < 0.001) and adolescents of 14 years-17 years (r = 0.356, P < 0.001) than for girls (r = 0.203, P < 0.001) and adolescents of 9 years-13 years (r = 0.221, P < 0.001), respectively. Serum ALT increased rapidly and followed a linear pattern from the point of BMI ≥20.5 kg/m2, and each increase of 1 kg/m2 in BMI range above 20.5 kg/m2 was averagely correlated with an increase of 2.71 U/L in ALT levels (P < 0.001). CONCLUSIONS We found a significant BMI-ALT relationship. BMI at 20.5 kg/m2 may be a cut-off for evaluating serum ALT. BMIs ≥27.1 kg/m2 for boys and ≥24.9 kg/m2 for girls were linked to an elevated ALT activity for Shenzhen adolescents.
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Affiliation(s)
- Zan Ding
- Institute of Low Carb Medicine, Baoan Central Hospital of Shenzhen, the Fifth Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, P. R. China
| | - Jing Zhang
- Department of Nursing, Baoan Central Hospital of Shenzhen, the Fifth Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, P. R. China
| | - Chang-Yu Deng
- Department of Preventive Medicine, Shantou University Medical College, Shantou, Guangdong, P. R. China
| | - Ying-Bin You
- Institute of Low Carb Medicine, Baoan Central Hospital of Shenzhen, the Fifth Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, P. R. China
- Department of Preventive Medicine, Shantou University Medical College, Shantou, Guangdong, P. R. China
| | - Hua Zhou
- Institute of Low Carb Medicine, Baoan Central Hospital of Shenzhen, the Fifth Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, P. R. China
- Corresponding author. Baoan Central Hospital of Shenzhen, the Fifth Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, P. R. China. Tel: +86-755-27956977; Fax: +86-755-27956977;
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Liu J, Au Yeung SL, Kwok MK, Leung JYY, Hui LL, Leung GM, Schooling CM. The effect of liver enzymes on body composition: A Mendelian randomization study. PLoS One 2020; 15:e0228737. [PMID: 32045441 PMCID: PMC7012438 DOI: 10.1371/journal.pone.0228737] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Accepted: 01/21/2020] [Indexed: 12/25/2022] Open
Abstract
Background Higher alanine transaminase (ALT), indicating poor liver function, is positively associated with diabetes but inversely associated with body mass index (BMI) in Mendelian randomization (MR) studies, suggesting liver function affects muscle mass. To clarify, we assessed the associations of liver enzymes with muscle and fat mass observationally with two-sample MR as a validation. Methods In the population-representative “Children of 1997” birth cohort (n = 3,455), we used multivariable linear regression to assess the adjusted associations of ALT and alkaline phosphatase (ALP) at ~17.5 years with muscle mass and body fat percentage observationally. Genetic variants predicting ALT, ALP and gamma glutamyltransferase (GGT) were applied to fat-free and fat mass in the UK Biobank (n = ~331,000) to obtain unconfounded MR estimates. Results Observationally, ALT was positively associated with muscle mass (0.11 kg per IU/L, 95% confidence interval (CI) 0.10 to 0.12) and fat percentage (0.15% per IU/L, 95% CI 0.13 to 0.17). ALP was inversely associated with muscle mass (-0.03 kg per IU/L, 95% CI -0.04 to -0.02) and fat percentage (-0.02% per IU/L, 95% CI -0.03 to -0.01). Using MR, ALT was inversely associated with fat-free mass (-0.41 kg per 100% in concentration, 95% CI -0.64 to -0.19) and fat mass (-0.58 kg per 100% in concentration, 95% CI -0.85 to -0.30). ALP and GGT were unclearly associated with fat-free mass or fat mass. Conclusion ALT reducing fat-free mass provides a possible pathway for the positive association of ALT with diabetes and suggests a potential target of intervention.
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Affiliation(s)
- Junxi Liu
- School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Shiu Lun Au Yeung
- School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Man Ki Kwok
- School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - June Yue Yan Leung
- School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Lai Ling Hui
- School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
- Department of Paediatrics, Faculty of Medicine, the Chinese University of Hong Kong, Hong Kong SAR, China
| | - Gabriel Matthew Leung
- School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - C. Mary Schooling
- School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
- City University of New York Graduate School of Public Health and Health Policy, New York, New York, United States of America
- * E-mail:
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Veniaminova E, Oplatchikova M, Bettendorff L, Kotenkova E, Lysko A, Vasilevskaya E, Kalueff AV, Fedulova L, Umriukhin A, Lesch KP, Anthony DC, Strekalova T. Prefrontal cortex inflammation and liver pathologies accompany cognitive and motor deficits following Western diet consumption in non-obese female mice. Life Sci 2019; 241:117163. [PMID: 31837337 DOI: 10.1016/j.lfs.2019.117163] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Revised: 12/08/2019] [Accepted: 12/09/2019] [Indexed: 12/15/2022]
Abstract
AIMS The high sugar and lipid content of the Western diet (WD) is associated with metabolic dysfunction, non-alcoholic steatohepatitis, and it is an established risk factor for neuropsychiatric disorders. Our previous studies reported negative effects of the WD on rodent emotionality, impulsivity, and sociability in adulthood. Here, we investigated the effect of the WD on motor coordination, novelty recognition, and affective behavior in mice as well as molecular and cellular endpoints in brain and peripheral tissues. MAIN METHODS Female C57BL/6 J mice were fed the WD for three weeks and were investigated for glucose tolerance, insulin resistance, liver steatosis, and changes in motor coordination, object recognition, and despair behavior in the swim test. Lipids and liver injury markers, including aspartate-transaminase, alanine-transaminase and urea were measured in blood. Serotonin transporter (SERT) expression, the density of Iba1-positive cells and concentration of malondialdehyde were measured in brain. KEY FINDINGS WD-fed mice exhibited impaired glucose tolerance and insulin resistance, a loss of motor coordination, deficits in novel object exploration and recognition, increased helplessness, dyslipidemia, as well as signs of a non-alcoholic steatohepatitis (NASH)-like syndrome: liver steatosis and increased liver injury markers. Importantly, these changes were accompanied by decreased SERT expression, elevated numbers of microglia cells and malondialdehyde levels in, and restricted to, the prefrontal cortex. SIGNIFICANCE The WD induces a spectrum of behaviors that are more reminiscent of ADHD and ASD than previously recognized and suggests that, in addition to the impairment of impulsivity and sociability, the consumption of a WD might be expected to exacerbate motor dysfunction that is also known to be associated with adult ADHD and ASD.
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Affiliation(s)
- Ekaterina Veniaminova
- Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Universiteitssingel 40, NL 6229ER Maastricht, the Netherlands; Laboratory of Psychiatric Neurobiology, Institute of Molecular Medicine and Department of Normal Physiology, Sechenov First Moscow State Medical University, Trubetskaya Str. 8, 119991 Moscow, Russia
| | - Margarita Oplatchikova
- Laboratory of Psychiatric Neurobiology, Institute of Molecular Medicine and Department of Normal Physiology, Sechenov First Moscow State Medical University, Trubetskaya Str. 8, 119991 Moscow, Russia
| | - Lucien Bettendorff
- Laboratory of Neurophysiology, GIGA-Neurosciences, University of Liège, Av. Hippocrate 15, 4000 Liège, Belgium
| | - Elena Kotenkova
- V.M. Gorbatov Federal Research Center for Food Systems of RAS, Tallalikhina Str. 26, 109316 Moscow, Russia
| | - Alexander Lysko
- Institute of General Pathology and Pathophysiology, Baltiyskaya Str. 8, 125315 Moscow, Russia
| | - Ekaterina Vasilevskaya
- V.M. Gorbatov Federal Research Center for Food Systems of RAS, Tallalikhina Str. 26, 109316 Moscow, Russia
| | - Allan V Kalueff
- School of Pharmacy, Southwest University, 400715 Chongqing, China; Institute of Translational Biomedicine, St. Petersburg State University, Universitetskaya Nab. 7-9, 199034 St. Petersburg, Russia; Ural Federal University, Mira Str. 19, 620002 Ekaterinburg, Russia
| | - Liliya Fedulova
- V.M. Gorbatov Federal Research Center for Food Systems of RAS, Tallalikhina Str. 26, 109316 Moscow, Russia
| | - Aleksei Umriukhin
- Laboratory of Psychiatric Neurobiology, Institute of Molecular Medicine and Department of Normal Physiology, Sechenov First Moscow State Medical University, Trubetskaya Str. 8, 119991 Moscow, Russia
| | - Klaus-Peter Lesch
- Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Universiteitssingel 40, NL 6229ER Maastricht, the Netherlands; Laboratory of Psychiatric Neurobiology, Institute of Molecular Medicine and Department of Normal Physiology, Sechenov First Moscow State Medical University, Trubetskaya Str. 8, 119991 Moscow, Russia; Division of Molecular Psychiatry, Laboratory of Translational Neuroscience, Center of Mental Health, University of Würzburg, Margarete-Höppel-Platz 1, 97080 Würzburg, Germany
| | - Daniel C Anthony
- Laboratory of Psychiatric Neurobiology, Institute of Molecular Medicine and Department of Normal Physiology, Sechenov First Moscow State Medical University, Trubetskaya Str. 8, 119991 Moscow, Russia; Department of Pharmacology, Oxford University, Mansfield Road, OX1 3QT Oxford, UK
| | - Tatyana Strekalova
- Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Universiteitssingel 40, NL 6229ER Maastricht, the Netherlands; Laboratory of Psychiatric Neurobiology, Institute of Molecular Medicine and Department of Normal Physiology, Sechenov First Moscow State Medical University, Trubetskaya Str. 8, 119991 Moscow, Russia; Division of Molecular Psychiatry, Laboratory of Translational Neuroscience, Center of Mental Health, University of Würzburg, Margarete-Höppel-Platz 1, 97080 Würzburg, Germany.
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Khoudari G, Singh A, Noureddin M, Fritze D, Lopez R, Asaad I, Lawitz E, Poordad F, Kowdley KV, Alkhouri N. Characterization of patients with both alcoholic and nonalcoholic fatty liver disease in a large United States cohort. World J Hepatol 2019; 11:710-718. [PMID: 31749901 PMCID: PMC6856017 DOI: 10.4254/wjh.v11.i10.710] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2019] [Revised: 08/03/2019] [Accepted: 10/15/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome (MetS) and is characterized by steatosis in the absence of significant alcohol consumption. However, MetS and significant alcohol intake coexist in certain individuals which may lead to the development of BAFLD.
AIM To assess the clinical characteristics of patients with both alcoholic and NAFLD (BAFLD) in a large cohort in the United States.
METHODS Adults from the National Health and Nutrition Examination Survey between 2003-2014 were included. NAFLD was diagnosed based on elevated alanine aminotransferase (ALT) and being overweight or obese in the absence of other liver diseases. BAFLD patients met the criteria for NAFLD but also had either MetS or type 2 diabetes and consumed excessive amounts of alcohol. Univariable and multivariable analysis were performed to assess differences between NAFLD and BAFLD and to compare severity based on a validated fibrosis score (FIB4 index).
RESULTS The prevalence of NAFLD was at 25.9% (95%CI; 25.1-26.8) and that of BAFLD was 0.84% (0.67, 1.02) which corresponds to an estimated 1.24 million Americans affected by BAFLD. Compared to NAFLD, patients with BAFLD were more likely to be male, smokers, have higher ALT, aspartate aminotransferase, triglycerides, and lower platelets; P < 0.01 for all. More importantly, after adjusting for MetS components, BAFLD patients were significantly more likely to have advanced fibrosis [adjusted OR (95%CI) based on FIB4 index > 2.67 was 3.2 (1.4, 7.0), P = 0.004].
CONCLUSION A significant percentage of the American general population is afflicted by BAFLD and these patients tend to have more advanced liver fibrosis.
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Affiliation(s)
- George Khoudari
- Department of Hospital Medicine, Cleveland Clinic Foundation, Cleveland, OH 44195, United States
| | - Amandeep Singh
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH 44195, United States
| | - Mazen Noureddin
- Department of Gastroenterology and Hepatology, Cedars Sinai Medical Center, Los Angeles, CA 90048, United States
| | - Danielle Fritze
- Department of General Surgery, Texas Liver Institute and University of Texas Health, San Antonio, TX 78215, United States
| | - Rocio Lopez
- Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH 44195, United States
| | - Imad Asaad
- Department of Gastroenterology, Metro Health System, Cleveland, OH 44109, United States
| | - Eric Lawitz
- Texas Liver Institute and University of Texas Health, San Antonio, TX 78215, United States
| | - Fred Poordad
- Texas Liver Institute and University of Texas Health, San Antonio, TX 78215, United States
| | - Kris V Kowdley
- Swedish Liver Care Network, Swedish Medical Center, Seattle, WA 98122, United States
| | - Naim Alkhouri
- Texas Liver Institute and University of Texas Health, San Antonio, TX 78215, United States
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Alanine Aminotransferase and Body Composition in Obese Men and Women. DISEASE MARKERS 2019; 2019:1695874. [PMID: 31534560 PMCID: PMC6732629 DOI: 10.1155/2019/1695874] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/25/2019] [Accepted: 07/30/2019] [Indexed: 12/11/2022]
Abstract
There is a known relationship between serum alanine aminotransferase (ALT) and obesity in humans, but the mechanism(s) are not clarified. This study investigated the associations between serum ALT and body composition in an overweight and obese population. The results are based on data from a previous randomized controlled trial treating obesity with vitamin D3. A sample of 448 overweight and obese individuals underwent dual-energy X-ray absorptiometry (DEXA) and measured serum ALT along with supplementary blood samples at study baseline. Body fat mass and lean mass indexes were calculated by dividing total body fat/lean weight (kg) by body height squared (kg/m2). ALT correlated with body mass index (BMI) in men but not women (r = 0.33, P < 0.0001 vs. r = 0.06, P = 0.29). In men, serum ALT correlated positively with fat mass index (r = 0.23, P = 0.004) and lean mass index (r = 0.32, P < 0.0001). In women, ALT correlated with lean mass index (r = 0.13, P = 0.031) but not fat mass index (r = 0.003, P = 0.96). In a multivariate model adjusted for age and fat mass index, a 1-unit increase in lean mass index associated with a 0.37 U/L higher ALT in the male subgroup (95% CI 0.024 to 0.040, P < 0.0001). In conclusion, serum ALT was associated with body fat mass index in men and with lean mass index in men and women in an overweight and obese population. The findings also demonstrate a gender difference in the role of fat.
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Zarrati M, Aboutaleb N, Cheshmazar E, Shoormasti RS, Razmpoosh E, Nasirinezhad F. The association of obesity and serum leptin levels with complete blood count and some serum biochemical parameters in Iranian overweight and obese individuals. Med J Islam Repub Iran 2019; 33:72. [PMID: 31696066 PMCID: PMC6825403 DOI: 10.34171/mjiri.33.72] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2017] [Indexed: 02/06/2023] Open
Abstract
Background: Obesity has been suggested to be well correlated with altered levels of complete blood count (CBC) parameters. In this study, the relationship of body mass index (BMI) and circulating leptin levels with CBC among obese and overweight adults was examined. Methods: CBC and biochemical parameters, WBC and hematological profiles, leptin levels, related factors to liver, and kidney and lipid profiles were measured among 184 obese and overweight people aged 18-60 years. Statistical analysis was performed using SPSS software. To assess the normality of data, the Kolmogorov-Smirnov test was used. Logarithmic transformation was performed for some variables with non-normal distribution. The association between 2 quantitative variables was measured using bivariate correlation (Pearson or Spearman). Pearson correlations and multiple regression analysis were performed to assess the correlation between variables. Simple and multiple regression analyses were performed to predict some variables. P- value <0.05 was considered significant. Results: Hematocrit, insulin, fasting blood sugar, uric acid, TG, LDL-C, VLDL-C, and ALT were positively correlated with BMI (p=0.041, r=0.149 for hematocrit; p≤0.001, r=0.520 for insulin; p≤0.001, r=0.363 for FBS; p≤0.001, r=0.309 for uric acid; p=0.015, r=0.189 for TG; p=0.030, r=161 for LDL-C; p=0.019, r=0.181 for VLDL-C; p≤0.001, r=0.299 for ALT), whereas urea and HDL-C were negatively correlated with BMI (p≤0.001, r=-0.368 for urea; p≤0.001, r=-0.297 for HDL-C). Moreover, LDL-C and insulin were positively correlated with leptin (P = 0.011, r = 0.194 for LDL-C, P = 0.013, r = 0.114 for insulin) and hematocrit, urea, creatinine, TG and VLDL-C were negatively correlated with leptin (p=0.040, r=-0.162 for hematocrit; p≤0.001, r=-0.305 for urea; p=0.007, r=-0.219 for creatinine; p=0.025, r=0.188 for TG; p=0.007, r=-0.218 for VLDL-C). Our analysis showed that white blood cell was positively correlated with leptin (β=17.36, p=0.048). Also, other CBC parameters had no significant correlations with BMI and leptin. Conclusion: According to the findings of this study, BMI had a negative association with urea and HDL-C, while BMI had a positive association with insulin, hematocrit, FBS, uric acid, TG, VLDL-C, LDL-C, and ALT. Furthermore, leptin had a negative association with hematocrit, creatinine, and urea, TG, VLDL-C and a positive association with LDL-C and insulin among the participants of this study.
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Affiliation(s)
- Mitra Zarrati
- Faculty of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Nahid Aboutaleb
- Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Elhameh Cheshmazar
- Faculty of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | | | - Elham Razmpoosh
- Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Farinaz Nasirinezhad
- Department of physiology, Basic Science Center, Iran University of Medical Sciences, Tehran, Iran
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Weight Gain and Liver Steatosis in Patients with Inflammatory Bowel Diseases. Nutrients 2019; 11:nu11020303. [PMID: 30717085 PMCID: PMC6412993 DOI: 10.3390/nu11020303] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2018] [Revised: 01/25/2019] [Accepted: 01/28/2019] [Indexed: 12/13/2022] Open
Abstract
Background and Aim: Most studies focused on the benefits of weight loss on hepatic steatosis and no studies have been specifically designed to assess the role of weight gain on the development of liver steatosis in patients affected by inflammatory bowel diseases. The aim of this study was to analyse the relation between weight change over time and liver steatosis in patients with inflammatory bowel diseases. Methods: We retrospectively evaluated a population of 89 ambulatory patients in clinical remission or affected by mild disease, as determined from disease activity indices, with at least one follow-up visit. Transient elastography was used to quantify liver steatosis. Results: A total of 49 individuals (55%) were overweight/obese at baseline. A significant difference in weight change was found between participants that improved, were stable and worsened, over a mean follow-up of four years. (−1.0 kg ± 4; 2.5 kg ± 6; and 5.4 kg ± 5; respectively, p = 0.009). We found a greater probability of worsening in the hepatic fat content in individuals who gained more than 6% of body weight than in those gaining less than this value (log–rank (Mantel–Cox) χ2 test = 9.85; df = 1; p = 0.002). Conclusions: A body weight gain of 6% increases the probability of deterioration in liver steatosis over a period of four years in patients with inflammatory bowel diseases. Weight gain prevention with lifestyle interventions may be the cornerstone treatment of these patients.
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Weta IW, Mahadewa TGB, Sutirtayasa WP, Subawa A, Sitanggang FP, Widyadharma IPE. The Comparison of Simple Anthropometric and Biochemical Parameters for Predicting Liver Steatosis in Obese Balinese Young Women. Open Access Maced J Med Sci 2018; 6:2062-2066. [PMID: 30559861 PMCID: PMC6290413 DOI: 10.3889/oamjms.2018.449] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Revised: 10/21/2018] [Accepted: 10/24/2018] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND: The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing globally. Early identification of liver steatosis (LS) status is critical to prevent the development of NAFLD into non-alcoholic steatohepatitis (NASH) fibrosis. AIM: This study aimed at exploring the validity of simple anthropometric and biochemical parameters to predict LS in young obese women. MATERIALS AND METHODS: This is a cross-sectional study involving 132 young obese women. We collected the data of measured waist circumference (WC), body mass index (BMI), serum triglyceride (TG), and gamma-glutamyltransferase (GGT). The lipid accumulation product (LAP) was designed from TG and WC variables. Fatty liver index (FLI) was calculated from TG, BMI, WC, and GGT variables. LS status was measured using ultrasonography assay. Statistical significance was set at p < 0.05. RESULTS: A positive correlation was found between BMI, WC, TG, GGT, LAP, FLI, and LS (p = 0.001). We found that BMI is a better predictor for LS to WC. Our multiple linear regression analysis revealed that BMI, GGT, and TG could predict 41.4% of LS. The validity (specificity, sensitivity, and odds ratio) of simple body fat parameters in predicting LS were as follows: BMI ≥ 30 kg/m2 (69.6%, 74.4%, and 6.21), WC ≥ 90 cm (67.4%, 70.0%, and 4.28), TG ≥ 100 mg/dL (70.6%, 70.0%, and 5.62) and GGT ≥ 20 μg/L (69.6%, 77.5%, and 7.87), as well as LAP ≥ 30 (82.6%, 70.0%, and 11.1), and FLI ≥ 2.5 (79.3%, 72.5%, and 10.1), significantly. CONCLUSION: Simple anthropometric and biochemical parameters (BMI, WC, and TG, GGT), are appropriately predicting LS as well as LAP, and FLI among obese Balinese young women.
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Affiliation(s)
- I Wayan Weta
- Department of Public Health, Preventive Medicine, and Clinical Nutrition, Faculty of Medicine, Udayana University, Bali, Indonesia
| | | | - Wayan Putu Sutirtayasa
- Department of Clinical Pathology, Faculty of Medicine, Udayana University, Bali, Indonesia
| | - Aan Subawa
- Department of Clinical Pathology, Faculty of Medicine, Udayana University, Bali, Indonesia
| | - Firman P Sitanggang
- Department of Radiology, Faculty of Medicine, Udayana University, Bali, Indonesia
| | - I Putu Eka Widyadharma
- Department of Neurology, Faculty of Medicine, Udayana University, Sanglah General Hospital, Bali, Indonesia
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Abstract
Background Little data is available on gamma-glutamyltransferase (GGT) and body fat distribution in healthy individuals. We examined whether GGT within normal range is prospectively associated with total body fat (TF) and regional body fat distribution. Methods We included 62 patients who were presented at Eureka Health and Research Foundation Clinic. GGT was measured by enzymatic photometry method. TF, android fat (AF), gynoid fat (GF) and android/gynoid ratio (A/G ratio) was assessed using Dual-energy X-ray absorptiometry. Regression coefficients and 95% Confidence Intervals were calculated using multivariate linear regression models adjusting for confounders. Results Mean value of GGT of the study population was 21.64U/L (ranging from 6 to 48 U/L). There was no association between GGT and TF. Increased GGT was associated with higher AF (top tertile relative to the lowest: ß=0.35; 95% CI: 0.19, 0.52), lower GF(top tertile relative to the lowest: ß=-0.48; 95%CI: -0.69,.-0.27) and higher AF/GF ratio (top tertile relative to the lowest: ß=0.04; 95%CI: 0.03, 0.06). Conclusions This study suggests that an increase in GGT concentrations is a sensitive and early biomarker of unfavorable body fat distribution.
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Affiliation(s)
- Viko Coku
- Eureka Health and Research Foundation Clinic, Tirana, Albania
| | - Xike Shkembi
- Eureka Health and Research Foundation Clinic, Tirana, Albania
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Choi KM, Han K, Park S, Chung HS, Kim NH, Yoo HJ, Seo JA, Kim SG, Kim NH, Baik SH, Park YG, Kim SM. Implication of liver enzymes on incident cardiovascular diseases and mortality: A nationwide population-based cohort study. Sci Rep 2018; 8:3764. [PMID: 29491346 PMCID: PMC5830612 DOI: 10.1038/s41598-018-19700-8] [Citation(s) in RCA: 60] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2017] [Accepted: 01/05/2018] [Indexed: 12/14/2022] Open
Abstract
Although liver enzymes, such as γ-glutamyltransferase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), have recently been suggested as risk factors for cardiovascular diseases (CVD), impact on mortality after myocardial infarction (MI) or ischemic stroke (IS) was not previously examined. Using a population-based, nationwide cohort database, we explored the implication of GGT and aminotransferases on the development of CVD and all-cause mortality during a median 9.1 years of follow-up. Among 16,624,006 Korean adults, both GGT and aminotransferases exhibited a positive relationship with MI, IS, and mortality in a multivariate adjusted model. ALT and AST showed U-shaped associations with mortality, whereas GGT showed a positive linear relationship with mortality. The risk of 1-year mortality after MI or IS was significantly higher in the highest quartile of GGT compared to the lowest quartile (HR, 1.46; 95% CI, 1.40-1.52). The implication of GGT on MI, IS, and mortality persisted regardless of traditional cardiovascular risk parameters. This study demonstrated the unique pattern of association of ALT, AST, and GGT with the development of CVD and all-cause mortality in the Korean population. In particular, GGT showed the most robust linear relationship with mortality before and after cardiovascular events independent of risk factors.
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Affiliation(s)
- Kyung Mook Choi
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea
| | - Kyungdo Han
- Department of Biostatistics, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Sanghyun Park
- Department of Biostatistics, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Hye Soo Chung
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea
| | - Nam Hoon Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea
| | - Hye Jin Yoo
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea
| | - Ji-A Seo
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea
| | - Sin Gon Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea
| | - Nan Hee Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea
| | - Sei Hyun Baik
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea
| | - Yong Gyu Park
- Department of Biostatistics, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Seon Mee Kim
- Department of Family Medicine, College of Medicine, Korea University, Seoul, Korea.
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Kuroki A, Sugita N, Komatsu S, Yokoseki A, Yoshihara A, Kobayashi T, Nakamura K, Momotsu T, Endo N, Sato K, Narita I, Yoshie H. Association of liver enzyme levels and alveolar bone loss: A cross-sectional clinical study in Sado Island. J Clin Exp Dent 2018; 10:e100-e106. [PMID: 29670725 PMCID: PMC5899799 DOI: 10.4317/jced.54555] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2017] [Accepted: 01/03/2018] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND The interaction of periodontopathic bacteria with host immune system induces the production of inflammatory mediators which leads to alveolar bone loss (ABL), the essential feature of periodontitis. Concurrently, periodontal diseases cause the elevation of blood cytokine levels, the alteration of gut microbiota and the dissemination of enterobacteria to the liver. Owing to these mechanisms, periodontal disease might be a risk for liver dysfunction. Several epidemiological studies have reported associations between periodontal diseases and liver dysfunction, although the association between ABL and liver dysfunction has not been investigated. This cross-sectional study determined if elevated serum liver enzyme levels were associated with ABL in Japanese adults. MATERIAL AND METHODS Japanese adults living on Sado Island who visited Sado General Hospital were invited to participate in the study. Participants over 40 years of age who underwent dental panoramic radiography and blood tests were included. Drinking and smoking habits were self-administered. After excluding patients with edentulous jaw, diagnosed liver diseases, and those on dialysis, data from 44 men and 66 women with a mean age of 73 years were analyzed. The average percentage of ABL for each participant was calculated for mesial and distal sites of all remaining teeth. The levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) were determined. Univariate analyses were performed to select covariates to be put in multivariate analyses. The association between elevated serum liver enzyme levels and the highest quartile of ABL were assessed by multiple logistic regression analysis. RESULTS After adjusting for covariates, no significant association was found between elevated serum AST, ALT, or GGT levels as dependent variables and the highest quartile of ABL as an explanatory variable. CONCLUSIONS There was no significant association between the elevation of serum liver enzyme levels and ABL in Japanese adults. Key words:Liver enzymes, dental panoramic radiography, alveolar bone loss, Japanese adults.
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Affiliation(s)
- Ayumi Kuroki
- DDS, Division of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Noriko Sugita
- Assistant Professor, DDS, PhD, Division of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | | | - Akio Yokoseki
- Specially appointed Associate Professor, MD, PhD, Department of Molecular Neuroscience, Resource Branch for Brain Disease Research, Brain Research Institute, Niigata, Japan
| | - Akihiro Yoshihara
- Professor, DDS, PhD, Department of Oral Health and Welfare, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Tetsuo Kobayashi
- Associate Professor, DDS, PhD, General Dentistry and Clinical Education Unit, Niigata University Medical and Dental Hospital, Niigata, Japan
| | - Kazutoshi Nakamura
- Professor, MD, PhD, Division of Preventive Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | | | - Naoto Endo
- Professor, MD, PhD, Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Science, Niigata, Japan
| | - Kenji Sato
- MD, PhD, Sado General Hospital, Niigata, Japan
| | - Ichiei Narita
- Professor, MD, PhD, Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Hiromasa Yoshie
- Professor, DDS, PhD, Division of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
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Belotta AF, Teixeira CR, Padovani CR, Rahal SC, Mayer MN, Mamprim MJ. Sonographic Evaluation of Liver Hemodynamic Indices in Overweight and Obese Dogs. J Vet Intern Med 2017; 32:181-187. [PMID: 29280193 PMCID: PMC5787168 DOI: 10.1111/jvim.14883] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2017] [Revised: 08/05/2017] [Accepted: 10/18/2017] [Indexed: 02/06/2023] Open
Abstract
Background Hepatic circulatory disturbances have been associated with obesity and fatty liver in humans. In the veterinary literature, however, there is limited information regarding the effects of different body condition scores (BCS) on liver hemodynamic indices in dogs. Objectives To investigate the influence of BCS on liver hemodynamic indices. Animals Fifty‐three client‐owned dogs of various breeds were included. Methods Prospective observational study. Dogs were divided into 3 BCS groups using a 5‐point scale: G1 – 12 ideal dogs, G2 – 21 overweight dogs, G3 – 20 obese dogs. Mean portal velocity (MPV), portal blood flow volume (PBFV), portal congestion index (PCI), hepatic artery resistivity index (HARI), and hepatic vein (HV) spectral wave were obtained by pulsed Doppler sonography. Alkaline phosphatase (ALP), gamma‐glutamyl transferase (GGT), and alanine aminotransferase (ALT) activities were determined. Liver enzymes activities and liver hemodynamic indices were compared among groups. Results Obese dogs had lower MPV, higher percentage of abnormal hepatic vein spectral wave and higher median ALP activity than did ideal dogs (P < 0.05). Overweight and obese dogs had lower PBFV than ideal dogs (P < 0.01). Overweight dogs had higher median GGT activity than ideal dogs (P < 0.05). No difference was observed for PCI, HARI and median ALT activity among the groups. Conclusions and Clinical Importance Obesity was associated with changes in portal vein indices and in HV spectral wave. These changes were accompanied by significant differences in some liver enzymes activities and could be a sign of early liver disease.
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Affiliation(s)
- A F Belotta
- Department of Animal Reproduction and Veterinary Radiology, São Paulo State University "Júlio de Mesquita Filho", Botucatu, SP, Brazil
| | - C R Teixeira
- Department of Veterinary Surgery and Anesthesiology, São Paulo State University "Júlio de Mesquita Filho", Botucatu, SP, Brazil
| | - C R Padovani
- School of Veterinary Medicine and Animal Science, São Paulo State University "Júlio de Mesquita Filho", Botucatu, SP, Brazil.,Department of Biostatistics, Biosciences Institute, São Paulo State University "Júlio de Mesquita Filho", Botucatu, SP, Brazil
| | - S C Rahal
- Department of Veterinary Surgery and Anesthesiology, São Paulo State University "Júlio de Mesquita Filho", Botucatu, SP, Brazil
| | - M N Mayer
- Department of Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada
| | - M J Mamprim
- Department of Animal Reproduction and Veterinary Radiology, São Paulo State University "Júlio de Mesquita Filho", Botucatu, SP, Brazil
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Abstract
OBJECTIVE Tesamorelin reduces visceral adipose tissue (VAT) in HIV. We investigated whether reductions in VAT with tesamorelin are associated with changes in alanine aminotransferase (ALT) and aspartate aminotransferase (AST). DESIGN AND METHODS We utilized data from two multicenter Phase III trials of tesamorelin among 806 HIV-infected patients with abdominal obesity. These studies showed that the majority of patients treated with tesamorelin are 'responders', defined a priori by the Food and Drug Administration as achieving at least 8% reduction in VAT. In the current analysis, we sought to examine the impact of VAT reduction on ALT and AST among patients participating in the Phase III trials with baseline elevated ALT or AST. Within this group, we compared changes in ALT and AST in VAT responders vs. nonresponders after 26 weeks of treatment, and then assessed the effects of drug discontinuation on these endpoints over a subsequent 26-week period. RESULTS At baseline, VAT was positively associated with ALT (P = 0.01). In study participants assigned to tesamorelin with baseline ALT or AST more than 30 U/l, VAT responders experienced greater reductions in ALT (-8.9 ± 22.6 vs. 1.4 ± 34.7 U/l, P = 0.004) and AST (-3.8 ± 12.9 vs. 0.4 ± 22.4 U/l, P = 0.04) compared with nonresponders over 26 weeks. This improvement among VAT responders persisted over 52 weeks even in those switched to placebo despite a partial reaccumulation of VAT. CONCLUSION A clinically significant VAT reduction with tesamorelin was associated with improved liver enzymes among HIV-infected patients with abdominal obesity and elevated baseline transaminases.
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Toita R, Kawano T, Fujita S, Murata M, Kang JH. Increased hepatic inflammation in a normal-weight mouse after long-term high-fat diet feeding. J Toxicol Pathol 2017; 31:43-47. [PMID: 29479139 PMCID: PMC5820102 DOI: 10.1293/tox.2017-0038] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2017] [Accepted: 08/07/2017] [Indexed: 12/22/2022] Open
Abstract
Among five C57BL/6 mice fed a high-fat diet (HFD) for 12 weeks, one mouse showed a body weight (BW) similar to normal diet (ND)-fed mice. We compared obesity-related parameters of three groups (ND-fed mice, one HFD-fed normal-weight mouse, and HFD-fed overweight mice), including visceral fat weight, serum levels of total cholesterol (TC), glucose, and aminotransferases (AST and ALT), adipocyte size, percentage of crown-like structures, severity of hepatic steatosis, and number of inflammatory foci. Compared to ND-fed mice, the HFD-fed normal-weight mouse exhibited a similar visceral fat weight, similar serum levels of glucose and aminotransferases, and a similar percentage of crown-like structures. On the other hand, the serum TC level, adipocyte size, and hepatic steatosis severity of the HFD-fed normal-weight mouse were intermediate between those of ND-fed mice and HFD-fed overweight mice. Interestingly, the number of hepatic inflammatory foci in the HFD-fed normal-weight mouse was remarkably increased compared with those in HFD-fed overweight mice. These results suggest that having BW or serum ALT levels within normal ranges may not guarantee absence of hepatic inflammation and that the HFD-fed normal-weight mouse can be used as an animal model for the study of liver inflammation, particularly in patients with normal BWs and/or serum ALT values.
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Affiliation(s)
- Riki Toita
- Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 1-8-31 Midorigaoka, Ikeda, Osaka 563-8577, Japan
| | - Takahito Kawano
- Department of Advanced Medical Initiatives, Faculty of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
| | - Satoshi Fujita
- Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 1-8-31 Midorigaoka, Ikeda, Osaka 563-8577, Japan
| | - Masaharu Murata
- Department of Advanced Medical Initiatives, Faculty of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
| | - Jeong-Hun Kang
- Division of Biopharmaceutics and Pharmacokinetics, National Cerebral and Cardiovascular Center Research Institute, 5-7-1, Fujishiro-dai, Suita, Osaka 565-8565, Japan
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Exercise training reduces alcohol consumption but does not affect HPA-axis activity in heavy drinkers. Physiol Behav 2017; 179:276-283. [PMID: 28684134 DOI: 10.1016/j.physbeh.2017.07.003] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2016] [Revised: 06/17/2017] [Accepted: 07/03/2017] [Indexed: 01/04/2023]
Abstract
BACKGROUND It has been suggested that physical exercise could have potential beneficial effects in substance abusers, which are based on both physiological and psychological theories. Although a few studies have examined the effect of exercise on alcohol intake and fitness in individuals with alcohol use disorders (AUDs), there is a gap in the literature concerning the physiological and biochemical mechanisms that could be affected by physical exercise in this population. PURPOSE The purpose of the present study was to examine physiological and biochemical responses to exercise after an 8-week supervised exercise training (ET) intervention in heavy drinkers. The investigation was mainly focused on the relationship among exercise, opioids, the hypothalamic-pituitary-adrenal axis (HPA) activity and heavy alcohol drinking. METHODS Eleven (Age: 30.3±3.5yrs; Body Mass Index: 28.4±0.86kg/m2) male heavy drinkers volunteered to participated in an 8-week supervised intervention of moderate intensity exercise (50-60% of Heart Rate Reserve). All participants were exhibiting low physical activity and used to drink heavily. Before intervention, the participants were asked to record their daily alcohol intake without changing their physical activity levels for 4weeks (control condition). During the 8-week supervised ET intervention, participants were recording their daily alcohol intake and were motivated to increase gradually the duration and frequency of ET. Blood samples were collected prior to and after 4weeks of the control condition, the day before the beginning of the ET intervention, and at the end of the 4th and 8th week of ET intervention. Blood samples were analyzed for β-E, epinephrine, norepinephrine, adrenocorticotropin, cortisol, gamma-glutamyl transferase (γ-GT), aspartate transaminase and alanine transaminase. Physiological and alcohol-related indices were also examined. RESULTS The 8-week supervised ET intervention resulted in reduced alcohol consumption, reduced γ-GT levels, and fitness improvement in heavy drinker. ET intervention did not significantly change the hormonal responses. CONCLUSION The results indicate that physical exercise could act as a healthy habit that can help individuals with AUDs reduce alcohol intake and improve health status; however, this is not related with changes in hormones associated with the HPA-axis.
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Sogabe M, Okahisa T, Nakasono M, Fukuno H, Miyamoto Y, Okada Y, Okazaki J, Miyoshi J, Tomonari T, Taniguchi T, Goji T, Kitamura S, Miyamoto H, Muguruma N, Takayama T. The differing influence of several factors on the development of fatty liver with elevation of liver enzymes between genders with metabolic syndrome: A cross-sectional study. PLoS One 2017; 12:e0177925. [PMID: 28574988 PMCID: PMC5456049 DOI: 10.1371/journal.pone.0177925] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2017] [Accepted: 05/05/2017] [Indexed: 12/01/2022] Open
Abstract
Background Nonalcoholic fatty liver disease (NAFLD) is known to be strongly associated with obesity, visceral fat, metabolic syndrome (MS), lifestyle, and lifestyle-related diseases in both males and females. However, the prevalence of NAFLD, MS, and clinical backgrounds is different between males and females. Objective We conducted a cross-sectional study to examine the differing influence of lifestyle-related factors and visceral fat on fatty liver (FL) with elevation of liver enzymes between males and females with MS. Methods We enrolled 42,134 persons who underwent a regular health check-up, and after excluding subjects who fulfilled excluding criteria, the remaining subjects were 2,110 persons with MS. We examined the differing influence of lifestyle-related factors and visceral fat on FL with elevation of alanine aminotransferase (ALT) (ALT elevation was defined as ALT level of ≥31 IU/l in the present study). Results The odds rations for FL with ALT elevation were as follows: WC, 1.83 (95% confidence interval (CI) 1.36–2.46); dyslipidemia, 1.89 (95% CI 1.34–2.68); hemoglobin A1c, 1.36 (95% CI 1.00–1.85); visceral fat type MS (V-type MS), 5.78 (95% CI 4.29–7.80); and light drinker, 0.56 (95% CI 0.41–0.78) in males with MS and BMI, 2.18 (95% CI 1.43–3.33); WC, 1.85 (95% CI 1.27–2.70); diastolic blood pressure, 1.69 (95% CI 1.16–2.45); triglyceride, 2.22 (95% CI 1.56–3.17); impaired glucose tolerance, 1.66 (95% CI 1.11–2.47); and V-type MS, 3.83 (95% CI 2.57–5.70) in females with MS. The prevalence of FL with ALT elevation and ALT was significantly higher in V-type MS than in the subcutaneous fat type MS in both males and females with MS (P < 0.001). Conclusion Although V-type MS and WC is a common significant predictor of an increased prevalence of FL with ALT elevation in both males and females with MS, gender, lifestyle-related factors, and MS type in individuals with MS should be considered for the development of FL with ALT elevation.
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Affiliation(s)
- Masahiro Sogabe
- Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
- Department of Gastroenterology, Kagawa Prefectural Cancer Detection Center, Takamatsu, Japan
- * E-mail:
| | - Toshiya Okahisa
- Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
| | - Masahiko Nakasono
- Department of Internal Medicine, Tsurugi Municipal Handa Hospital, Tokushima, Japan
| | - Hiroshi Fukuno
- Department of Internal Medicine, Higashi Tokushima Medical Center, National Hospital Organization, Tokushima, Japan
| | - Yoshihiko Miyamoto
- Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
| | - Yasuyuki Okada
- Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
| | - Jun Okazaki
- Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
| | - Jinsei Miyoshi
- Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
| | - Tetsu Tomonari
- Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
| | - Tatsuya Taniguchi
- Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
| | - Takahiro Goji
- Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
| | - Shinji Kitamura
- Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
| | - Hiroshi Miyamoto
- Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
| | - Naoki Muguruma
- Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
| | - Tetsuji Takayama
- Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
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