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Zhang N, Liao H, Lin Z, Tang Q. Insights into the Role of Glutathione Peroxidase 3 in Non-Neoplastic Diseases. Biomolecules 2024; 14:689. [PMID: 38927092 PMCID: PMC11202029 DOI: 10.3390/biom14060689] [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: 05/07/2024] [Revised: 06/03/2024] [Accepted: 06/05/2024] [Indexed: 06/28/2024] Open
Abstract
Reactive oxygen species (ROSs) are byproducts of normal cellular metabolism and play pivotal roles in various physiological processes. Disruptions in the balance between ROS levels and the body's antioxidant defenses can lead to the development of numerous diseases. Glutathione peroxidase 3 (GPX3), a key component of the body's antioxidant system, is an oxidoreductase enzyme. GPX3 mitigates oxidative damage by catalyzing the conversion of hydrogen peroxide into water. Beyond its antioxidant function, GPX3 is vital in regulating metabolism, modulating cell growth, inducing apoptosis and facilitating signal transduction. It also serves as a significant tumor suppressor in various cancers. Recent studies have revealed aberrant expression of GPX3 in several non-neoplastic diseases, associating it with multiple pathological processes. This review synthesizes the current understanding of GPX3 expression and regulation, highlighting its extensive roles in noncancerous diseases. Additionally, this paper evaluates the potential of GPX3 as a diagnostic biomarker and explores emerging therapeutic strategies targeting this enzyme, offering potential avenues for future clinical treatment of non-neoplastic conditions.
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Affiliation(s)
- Nan Zhang
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; (N.Z.); (H.L.)
- Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan 430060, China
| | - Haihan Liao
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; (N.Z.); (H.L.)
- Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan 430060, China
| | - Zheng Lin
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; (N.Z.); (H.L.)
- Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan 430060, China
| | - Qizhu Tang
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; (N.Z.); (H.L.)
- Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan 430060, China
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Yamanaka Y, Tajima T, Tsujimura Y, Naito T, Mano Y, Tsukamoto M, Zenke Y, Sakai A. Adiponectin inhibits fibrosis of the palmar aponeurosis in Dupuytren's contracture in male patients. Bone Joint Res 2023; 12:486-493. [PMID: 37536684 PMCID: PMC10400293 DOI: 10.1302/2046-3758.128.bjr-2022-0449.r1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/05/2023] Open
Abstract
Aims Dupuytren's contracture is characterized by increased fibrosis of the palmar aponeurosis, with eventual replacement of the surrounding fatty tissue with palmar fascial fibromatosis. We hypothesized that adipocytokines produced by adipose tissue in contact with the palmar aponeurosis might promote fibrosis of the palmar aponeurosis. Methods We compared the expression of the adipocytokines adiponectin and leptin in the adipose tissue surrounding the palmar aponeurosis of male patients with Dupuytren's contracture, and of male patients with carpal tunnel syndrome (CTS) as the control group. We also examined the effects of adiponectin on fibrosis-related genes and proteins expressed by fibroblasts in the palmar aponeurosis of patients with Dupuytren's contracture. Results Adiponectin expression in the adipose tissue surrounding the palmar aponeurosis was significantly lower in patients with Dupuytren's contracture than in those with CTS. The expression of fibrosis-related genes and proteins, such as types 1 and 3 collagen and α-smooth muscle actin, was suppressed in a concentration-dependent manner by adding AdipoRon, an adiponectin receptor agonist. The expression of fibrosis-related genes and proteins was also suppressed by AdipoRon in the in vitro model of Dupuytren's contracture created by adding TGF-β to normal fibroblasts collected from patients with CTS. Conclusion Fibrosis of the palmar aponeurosis in Dupuytren's contracture in males may be associated with adiponectin expression in the adipose tissue surrounding the palmar aponeurosis. Although fibroblasts within the palmar aponeurosis are often the focus of attention when elucidating the pathogenesis of Dupuytren's contracture, adiponectin expression in adipose tissues warrants closer attention in future research.
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Affiliation(s)
- Yoshiaki Yamanaka
- Department of Orthopaedic Surgery, School of Medicine, University of Occupational and Environmental Health, Fukuoka, Japan
| | - Takafumi Tajima
- Department of Orthopaedic Surgery, School of Medicine, University of Occupational and Environmental Health, Fukuoka, Japan
| | - Yoshitaka Tsujimura
- Department of Orthopaedic Surgery, School of Medicine, University of Occupational and Environmental Health, Fukuoka, Japan
| | - Toichiro Naito
- Department of Orthopaedic Surgery, School of Medicine, University of Occupational and Environmental Health, Fukuoka, Japan
| | - Yosuke Mano
- Department of Orthopaedic Surgery, School of Medicine, University of Occupational and Environmental Health, Fukuoka, Japan
| | - Manabu Tsukamoto
- Department of Orthopaedic Surgery, School of Medicine, University of Occupational and Environmental Health, Fukuoka, Japan
| | - Yukichi Zenke
- Department of Orthopaedic Surgery, School of Medicine, University of Occupational and Environmental Health, Fukuoka, Japan
| | - Akinori Sakai
- Department of Orthopaedic Surgery, School of Medicine, University of Occupational and Environmental Health, Fukuoka, Japan
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Chikamatsu M, Watanabe H, Shintani Y, Murata R, Miyahisa M, Nishinoiri A, Imafuku T, Takano M, Arimura N, Yamada K, Kamimura M, Mukai B, Satoh T, Maeda H, Maruyama T. Albumin-fused long-acting FGF21 analogue for the treatment of non-alcoholic fatty liver disease. J Control Release 2023; 355:42-53. [PMID: 36690035 DOI: 10.1016/j.jconrel.2023.01.039] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 01/03/2023] [Accepted: 01/14/2023] [Indexed: 01/25/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) currently affects about 25% of the world's population, and the numbers continue to rise as the number of obese patients increases. However, there are currently no approved treatments for NAFLD. This study reports on the evaluation of the therapeutic effect of a recombinant human serum albumin-fibroblast growth factor 21 analogue fusion protein (HSA-FGF21) on the pathology of NAFLD that was induced by using two high-fat diets (HFD), HFD-60 and STHD-01. The HFD-60-induced NAFLD model mice with obesity, insulin resistance, dyslipidemia and hepatic lipid accumulation were treated with HSA-FGF21 three times per week for 4 weeks starting at 12 weeks after the HFD-60 feeding. The administration of HSA-FGF21 suppressed the increased body weight, improved hyperglycemia, hyperinsulinemia, and showed a decreased accumulation of plasma lipid and hepatic lipid levels. The elevation of C16:0, C18:0 and C18:1 fatty acids in the liver that were observed in the HFD-60 group was recovered by the HSA-FGF21 administration. The increased expression levels of the hepatic fatty acid uptake receptor (CD36) and fatty acid synthase (SREBP-1c, FAS, SCD-1, Elovl6) were also suppressed. In adipose tissue, HSA-FGF21 caused an improved adipocyte hypertrophy, a decrease in the levels of inflammatory cytokines and induced the expression of adiponectin and thermogenic factors. The administration of HSA-FGF21 to the STHD-01-induced NAFLD model mice resulted in suppressed plasma ALT and AST levels, oxidative stress, inflammatory cell infiltration and fibrosis. Together, HSA-FGF21 has some potential for use as a therapeutic agent for the treatment of NAFLD.
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Affiliation(s)
- Mayuko Chikamatsu
- Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan
| | - Hiroshi Watanabe
- Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
| | - Yuhi Shintani
- Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan
| | - Ryota Murata
- Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan
| | - Masako Miyahisa
- Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan
| | - Ayano Nishinoiri
- Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan
| | - Tadashi Imafuku
- Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan
| | - Mei Takano
- Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan
| | - Nanaka Arimura
- Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan
| | - Kohichi Yamada
- Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan
| | - Miya Kamimura
- Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan
| | - Baki Mukai
- Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan
| | - Takao Satoh
- Kumamoto Industrial Research Institute, Kumamoto, Japan
| | - Hitoshi Maeda
- Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan
| | - Toru Maruyama
- Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan
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Li Z, Zhu Z, Liu Y, Liu Y, Zhao H. Function and regulation of GPX4 in the development and progression of fibrotic disease. J Cell Physiol 2022; 237:2808-2824. [PMID: 35605092 DOI: 10.1002/jcp.30780] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Revised: 04/21/2022] [Accepted: 04/26/2022] [Indexed: 02/06/2023]
Abstract
Fibrosis is a common feature of fibrotic diseases that poses a serious threat to global health due to high morbidity and mortality in developing countries. There exist some chemical compounds and biomolecules associated with the development of fibrosis, including cytokines, hormones, and enzymes. Among them, glutathione peroxidase 4 (GPX4), as a selenoprotein antioxidant enzyme, is widely found in the embryo, testis, brain, liver, heart, and photoreceptor cells. Moreover, it is shown that GPX4 elicits diverse biological functions by suppressing phospholipid hydroperoxide at the expense of decreased glutathione (GSH), including loss of neurons, autophagy, cell repair, inflammation, ferroptosis, apoptosis, and oxidative stress. Interestingly, these processes are intimately related to the occurrence of fibrotic disease. Recently, GPX4 has been reported to exhibit a decline in fibrotic disease and inhibit fibrosis, suggesting that alterations of GPX4 can change the course or dictate the outcome of fibrotic disease. In this review, we summarize the role and underlying mechanisms of GPX4 in fibrosis diseases such as lung fibrosis, liver fibrosis, kidney fibrosis, cardiac fibrosis, and myelofibrosis.
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Affiliation(s)
- Zhaobing Li
- Department of Cardiology, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, Hunnan, China
| | - Zigui Zhu
- Department of Intensive Care Units, The Affiliated Nanhua Hospital, Hengyang Medical school, University of South China, Hengyang, Hunnan, China
| | - Yulu Liu
- Department of Intensive Care Units, The Affiliated Nanhua Hospital, Hengyang Medical school, University of South China, Hengyang, Hunnan, China
| | - Yannan Liu
- School of Nursing, Hunan University of Medicine, Huaihua, Hunan, China
| | - Hong Zhao
- School of Nursing, Hengyang Medical School, University of South China, Hengyang, Hunan, China
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Ou MY, Zhang H, Tan PC, Zhou SB, Li QF. Adipose tissue aging: mechanisms and therapeutic implications. Cell Death Dis 2022; 13:300. [PMID: 35379822 PMCID: PMC8980023 DOI: 10.1038/s41419-022-04752-6] [Citation(s) in RCA: 107] [Impact Index Per Article: 35.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 03/03/2022] [Accepted: 03/18/2022] [Indexed: 01/10/2023]
Abstract
Adipose tissue, which is the crucial energy reservoir and endocrine organ for the maintenance of systemic glucose, lipid, and energy homeostasis, undergoes significant changes during aging. These changes cause physiological declines and age-related disease in the elderly population. Here, we review the age-related changes in adipose tissue at multiple levels and highlight the underlying mechanisms regulating the aging process. We also discuss the pathogenic pathways of age-related fat dysfunctions and their systemic negative consequences, such as dyslipidemia, chronic general inflammation, insulin resistance, and type 2 diabetes (T2D). Age-related changes in adipose tissue involve redistribution of deposits and composition, in parallel with the functional decline of adipocyte progenitors and accumulation of senescent cells. Multiple pathogenic pathways induce defective adipogenesis, inflammation, aberrant adipocytokine production, and insulin resistance, leading to adipose tissue dysfunction. Changes in gene expression and extracellular signaling molecules regulate the aging process of adipose tissue through various pathways. In addition, adipose tissue aging impacts other organs that are infiltrated by lipids, which leads to systemic inflammation, metabolic system disruption, and aging process acceleration. Moreover, studies have indicated that adipose aging is an early onset event in aging and a potential target to extend lifespan. Together, we suggest that adipose tissue plays a key role in the aging process and is a therapeutic target for the treatment of age-related disease, which deserves further study to advance relevant knowledge.
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Affiliation(s)
- Min-Yi Ou
- Department of Plastic & Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 200011, Shanghai, China
| | - Hao Zhang
- Department of Plastic & Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 200011, Shanghai, China
| | - Poh-Ching Tan
- Department of Plastic & Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 200011, Shanghai, China
| | - Shuang-Bai Zhou
- Department of Plastic & Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 200011, Shanghai, China.
| | - Qing-Feng Li
- Department of Plastic & Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 200011, Shanghai, China.
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Applications of Stem Cell Therapy and Adipose-Derived Stem Cells for Skin Repair. CURRENT DERMATOLOGY REPORTS 2022. [DOI: 10.1007/s13671-022-00357-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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Mizusawa N, Harada N, Iwata T, Ohigashi I, Itakura M, Yoshimoto K. Identification of protease serine S1 family member 53 as a mitochondrial protein in murine islet beta cells. Islets 2022; 14:1-13. [PMID: 34636707 PMCID: PMC8812782 DOI: 10.1080/19382014.2021.1982325] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
The aim of this study was to identify genes that are specifically expressed in pancreatic islet β-cells (hereafter referred to as β-cells). Large-scale complementary DNA-sequencing analysis was performed for 3,429 expressed sequence tags derived from murine MIN6 β-cells, through homology comparisons using the GenBank database. Three individual ESTs were found to code for protease serine S1 family member 53 (Prss53). Prss53 mRNA is processed into both a short and long form, which encode 482 and 552 amino acids, respectively. Transient overexpression of myc-tagged Prss53 in COS-7 cells showed that Prss53 was strongly associated with the luminal surfaces of organellar membranes and that it underwent signal peptide cleavage and N-glycosylation. Immunoelectron microscopy and western blotting revealed that Prss53 localized to mitochondria in MIN6 cells. Short hairpin RNA-mediated Prss53 knockdown resulted in Ppargc1a downregulation and Ucp2 and Glut2 upregulation. JC-1 staining revealed that the mitochondria were depolarized in Prss53-knockdown MIN6 cells; however, no change was observed in glucose-stimulated insulin secretion. Our results suggest that mitochondrial Prss53 expression plays an important role in maintaining the health of β-cells.
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Affiliation(s)
- Noriko Mizusawa
- Department of Medical Pharmacology, Institute of Biomedical Sciences, Tokushima University, Tokushima, Japan
- CONTACT Noriko Mizusawa Department of Oral Bioscience, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-Kuramoto-cho, Tokushima City770-8504, Japan
| | - Nagakatsu Harada
- Department of Health and Nutrition, Faculty of Nursing and Nutrition, The University of Shimane, Shimane, Japan
| | - Takeo Iwata
- Department of Functional Morphology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Japan
| | - Izumi Ohigashi
- Division of Experimental Immunology, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan
| | - Mitsuo Itakura
- Division of Genetic Information, Institute for Genome Research, Tokushima University, Tokushima, Japan
| | - Katsuhiko Yoshimoto
- Department of Medical Pharmacology, Institute of Biomedical Sciences, Tokushima University, Tokushima, Japan
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Bosch E, Hebebrand M, Popp B, Penger T, Behring B, Cox H, Towner S, Kraus C, Wilson WG, Khan S, Krumbiegel M, Ekici AB, Uebe S, Trollmann R, Woelfle J, Reis A, Vasileiou G. BDV Syndrome: An Emerging Syndrome With Profound Obesity and Neurodevelopmental Delay Resembling Prader-Willi Syndrome. J Clin Endocrinol Metab 2021; 106:3413-3427. [PMID: 34383079 DOI: 10.1210/clinem/dgab592] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Indexed: 12/17/2022]
Abstract
CONTEXT CPE encodes carboxypeptidase E, an enzyme that converts proneuropeptides and propeptide hormones to bioactive forms. It is widely expressed in the endocrine and central nervous system. To date, 4 individuals from 2 families with core clinical features including morbid obesity, neurodevelopmental delay, and hypogonadotropic hypogonadism, harboring biallelic loss-of-function (LoF) CPE variants, have been reported. OBJECTIVE We describe 4 affected individuals from 3 unrelated consanguineous families, 2 siblings of Syrian, 1 of Egyptian, and 1 of Pakistani descent, all harboring novel homozygous CPE LoF variants. METHODS After excluding Prader-Willi syndrome (PWS), exome sequencing was performed in both Syrian siblings. The variants identified in the other 2 individuals were reported as research variants in a large-scale exome study and in the ClinVar database. Computational modeling of all possible missense alterations allowed assessing CPE tolerance to missense variants. RESULTS All affected individuals were severely obese with neurodevelopmental delay and other endocrine anomalies. Three individuals from 2 families shared the same CPE homozygous truncating variant c.361C > T, p.(Arg121*), while the fourth carried the c.994del, p.(Ser333Alafs*22) variant. Comparison of clinical features with previously described cases and standardization according to the Human Phenotype Ontology terms indicated a recognizable clinical phenotype, which we termed Blakemore-Durmaz-Vasileiou (BDV) syndrome. Computational analysis indicated high conservation of CPE domains and intolerance to missense changes. CONCLUSION Biallelic truncating CPE variants are associated with BDV syndrome, a clinically recognizable monogenic recessive syndrome with childhood-onset obesity, neurodevelopmental delay, hypogonadotropic hypogonadism, and hypothyroidism. BDV syndrome resembles PWS. Our findings suggest missense variants may also be clinically relevant.
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Affiliation(s)
- Elisabeth Bosch
- Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany
| | - Moritz Hebebrand
- Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany
| | - Bernt Popp
- Institute of Human Genetics, University of Leipzig Hospitals and Clinics, 04103 Leipzig, Germany
| | - Theresa Penger
- Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, 91054 Erlangen, Germany
| | - Bettina Behring
- Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, 91054 Erlangen, Germany
| | - Helen Cox
- West Midlands Regional Clinical Genetics Unit, Birmingham Women's Hospital, Edgbaston, Birmingham B15 2TG, UK
| | - Shelley Towner
- Department of Pediatrics, Division of Genetics, University of Virginia, Charlottesville, Virginia 22908, USA
| | - Cornelia Kraus
- Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany
| | - William G Wilson
- Department of Pediatrics, Division of Genetics, University of Virginia, Charlottesville, Virginia 22908, USA
| | - Shagufta Khan
- West Midlands Regional Clinical Genetics Unit, Birmingham Women's Hospital, Edgbaston, Birmingham B15 2TG, UK
| | - Mandy Krumbiegel
- Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany
| | - Arif B Ekici
- Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany
| | - Steffen Uebe
- Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany
| | - Regina Trollmann
- Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, 91054 Erlangen, Germany
| | - Joachim Woelfle
- Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, 91054 Erlangen, Germany
| | - André Reis
- Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany
| | - Georgia Vasileiou
- Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany
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Taouis M, Benomar Y. Is resistin the master link between inflammation and inflammation-related chronic diseases? Mol Cell Endocrinol 2021; 533:111341. [PMID: 34082045 DOI: 10.1016/j.mce.2021.111341] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Revised: 05/25/2021] [Accepted: 05/28/2021] [Indexed: 01/07/2023]
Abstract
Resistin has been firstly discovered in mice and was identified as an adipose tissue-secreted hormone or adipokine linking obesity and insulin resistance. In humans, resistin has been characterized as a hormone expressed and secreted by Immune cells especially by macrophages, and was linked to many inflammatory responses including inflammation of adipose tissue due to macrophages' infiltration. Human and mouse resistin display sequence and structural similarities and also dissimilarities that could explain their different expression pattern. In mice, strong pieces of evidence clearly associated high resistin plasma levels to obesity and insulin resistance suggesting that resistin could play an important role in the onset and progression of obesity and insulin resistance via resistin-induced inflammation. In humans, the link between resistin and obesity/insulin resistance is still a matter of debate and needs more epidemiological studies. Also, resistin has been linked to other chronic diseases such as cardiovascular diseases and cancers where resistin has been proposed in many studies as a biological marker.
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Affiliation(s)
- Mohammed Taouis
- Molecular Neuroendocrinology of Food Intake (NMPA), UMR 9197, University of Paris-Saclay, Orsay, France; NMPA, Dept. Development, Evolution and Cell Signaling, Paris-Saclay Institute of Neurosciences (NeuroPSI) CNRS UMR 9197, Orsay, France.
| | - Yacir Benomar
- Molecular Neuroendocrinology of Food Intake (NMPA), UMR 9197, University of Paris-Saclay, Orsay, France; NMPA, Dept. Development, Evolution and Cell Signaling, Paris-Saclay Institute of Neurosciences (NeuroPSI) CNRS UMR 9197, Orsay, France
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10
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Obesity and aging: Molecular mechanisms and therapeutic approaches. Ageing Res Rev 2021; 67:101268. [PMID: 33556548 DOI: 10.1016/j.arr.2021.101268] [Citation(s) in RCA: 114] [Impact Index Per Article: 28.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Revised: 01/19/2021] [Accepted: 02/02/2021] [Indexed: 02/08/2023]
Abstract
The epidemic of obesity is a major challenge for health policymakers due to its far-reaching effects on population health and potentially overwhelming financial burden on healthcare systems. Obesity is associated with an increased risk of developing acute and chronic diseases, including hypertension, stroke, myocardial infarction, cardiovascular disease, diabetes, and cancer. Interestingly, the metabolic dysregulation associated with obesity is similar to that observed in normal aging, and substantial evidence suggests the potential of obesity to accelerate aging. Therefore, understanding the mechanism of fat tissue dysfunction in obesity could provide insights into the processes that contribute to the metabolic dysfunction associated with the aging process. Here, we review the molecular and cellular mechanisms underlying both obesity and aging, and how obesity and aging can predispose individuals to chronic health complications. The potential of lifestyle and pharmacological interventions to counter obesity and obesity-related pathologies, as well as aging, is also addressed.
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New cell delivery system CellSaic with adipose-derived stromal cells promotes functional angiogenesis in critical limb ischemia model mice. J Artif Organs 2021; 24:343-350. [PMID: 33656644 PMCID: PMC8380570 DOI: 10.1007/s10047-021-01254-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Accepted: 02/02/2021] [Indexed: 10/29/2022]
Abstract
Current therapies for patients with critical limb ischemia have not reduced amputation risk owing to poor cell engraftment. The recombinant peptide Cellnest increases the engraftment rate of administered cells by forming a complex with the cells (CellSaic). We hypothesized that CellSaic containing adipose-derived stromal cells (ADSCs) could improve lower limb blood flow better than ADSCs alone, resulting in better transplanted cell engraftment. ADSCs were extracted from 8-week-old C57BL/6N mice. Thirty-two critical limb ischemia model mice were established by ligating femoral arteries. They were divided into CellSaic (n = 11), ADSC (n = 10), saline (n = 9), and Cellnest (n = 9) groups. Blood flow rate (affected side blood flow / healthy side blood flow × 100%) was evaluated using a laser Doppler blood flow meter every week. Mice were euthanized on day 28 for histological evaluation. Compared with the ADSC group (54.5 ± 17.2%), treated side blood flow rate of the CellSaic group (78.0 ± 24.9%) showed significant improvement on day 28 after administration (p < 0.05). CD31 staining showed significantly higher number of capillary vessels in the CellSaic group (53.0 ± 8.9 cells/mm3) than in the ADSC group (43.0 ± 6.8 cells/mm3) (p < 0.05). Fluorescent staining showed significantly higher number of arterioles containing both CD31 and αSMA double-positive cells in the CellSaic group than in the ADSC group (p < 0.05). CellSaic containing ADSCs exhibited superiority to ADSC transplantation alone in promoting functional angiogenesis, suggesting its potential in improving clinical outcomes of angiogenic therapy for ischemic limbs.
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Buday K, Conrad M. Emerging roles for non-selenium containing ER-resident glutathione peroxidases in cell signaling and disease. Biol Chem 2020; 402:271-287. [PMID: 33055310 DOI: 10.1515/hsz-2020-0286] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Accepted: 10/08/2020] [Indexed: 12/16/2022]
Abstract
Maintenance of cellular redox control is pivotal for normal cellular functions and cell fate decisions including cell death. Among the key cellular redox systems in mammals, the glutathione peroxidase (GPX) family of proteins is the largest conferring multifaceted functions and affecting virtually all cellular processes. The endoplasmic reticulum (ER)-resident GPXs, designated as GPX7 and GPX8, are the most recently added members of this family of enzymes. Recent studies have provided exciting insights how both enzymes support critical processes of the ER including oxidative protein folding, maintenance of ER redox control by eliminating H2O2, and preventing palmitic acid-induced lipotoxicity. Consequently, numerous pathological conditions, such as neurodegeneration, cancer and metabolic diseases have been linked with altered GPX7 and GPX8 expression. Studies in mice have demonstrated that loss of GPX7 leads to increased differentiation of preadipocytes, increased tumorigenesis and shortened lifespan. By contrast, GPX8 deficiency in mice results in enhanced caspase-4/11 activation and increased endotoxic shock in colitis model. With the increasing recognition that both types of enzymes are dysregulated in various tumor entities in man, we deem a review of the emerging roles played by GPX7 and GPX8 in health and disease development timely and appropriate.
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Affiliation(s)
- Katalin Buday
- Institute of Metabolism and Cell Death, Helmholtz Zentrum München, Ingolstädter Landstr. 1, D-85764Neuherberg, Germany
| | - Marcus Conrad
- Institute of Metabolism and Cell Death, Helmholtz Zentrum München, Ingolstädter Landstr. 1, D-85764Neuherberg, Germany.,National Research Medical University, Laboratory of Experimental Oncology, Ostrovityanova 1, 117997Moscow, Russia
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13
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Yang X, Ma Y, Zhao Z, Zhen S, Wen D. Complement C1q as a Potential Biomarker for Obesity and Metabolic Syndrome in Chinese Adolescents. Front Endocrinol (Lausanne) 2020; 11:586440. [PMID: 33329392 PMCID: PMC7735390 DOI: 10.3389/fendo.2020.586440] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Accepted: 10/20/2020] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Complement C1q (C1q) has been confirmed to be related to obesity, metabolic syndrome (MetS), and its components. However, human data regarding the associations are relatively scarce. This study aimed to investigate associations of C1q with obesity as well as MetS in Chinese adolescents. METHODS A total of 1,191 Chinese adolescents aged 13-18 years were enrolled in this study. The biochemical and anthropometric variables of all the subjects were evaluated using standardized procedures. C1q was measured using the immunoturbidometric assay. The relationship between C1q and obesity or MetS was analyzed using multiple regression analyses. RESULTS Obesity was more prevalent among participants in the highest tertile than in the lowest tertile of C1q levels. The highest tertile of C1q was related to a greater effect on the risk of MetS, and its trend test was statistically significant. Except for hyperglycemia, the prevalence of other components of MetS significantly increased relative to an increase in C1q tertile. Receiver operating characteristic (ROC) curve analysis of C1q for predicting adolescents with MetS illustrated that the area under the curve (AUC) was 0.82 [95% confidence interval (CI): 0.76, 0.88; P<0.001] in the total population after adjusting for confounders. CONCLUSIONS This study observed a significantly higher prevalence of obesity and MetS features in adolescents with high C1q. The findings of the current study also reported a significant relationship between C1q levels and MetS components [except for fasting plasma glucose (FPG)] in Chinese adolescents. C1q may represent a biomarker for predicting obesity or MetS in adolescents.
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Affiliation(s)
- Xuelian Yang
- Institute of Health Sciences, China Medical University, Shenyang, China
| | - Yanan Ma
- School of Public Health, China Medical University, Shenyang, China
| | - Zhongyi Zhao
- Department of Health Management, Shengjing Hospital of China Medical University, Shenyang, China
| | - Shihan Zhen
- Institute of Health Sciences, China Medical University, Shenyang, China
| | - Deliang Wen
- Institute of Health Sciences, China Medical University, Shenyang, China
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Maeda N, Funahashi T, Matsuzawa Y, Shimomura I. Adiponectin, a unique adipocyte-derived factor beyond hormones. Atherosclerosis 2019; 292:1-9. [PMID: 31731079 DOI: 10.1016/j.atherosclerosis.2019.10.021] [Citation(s) in RCA: 68] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2019] [Revised: 10/01/2019] [Accepted: 10/31/2019] [Indexed: 12/11/2022]
Abstract
Visceral fat accumulation has a marked impact on atherosclerotic cardiovascular diseases and metabolic syndrome clustering diabetes, dyslipidemia, and hypertension. Adiponectin, an adipocyte-derived circulating protein, is a representative adipocytokine and uniquely possesses two major properties: 1) its circulating concentration is approximately 3-6 orders of magnitude greater than ordinary hormones and cytokines; 2) its concentration inversely correlates with body fat mass despite its adipocyte-specific production. Low serum levels of adiponectin correlate with cardiometabolic diseases. Extensive experimental evidence has demonstrated that adiponectin possesses multiple properties, such as anti-atherosclerotic, anti-diabetic, and anti-inflammatory activities. It has been shown to play a central role against the development of metabolic syndrome and its complications. However, even approximately 25 years after its discovery, the properties of adiponectin, including how and why it exerts multiple beneficial effects on various tissues and/or organs, remain unclear. Furthermore, the mechanisms responsible for the very high circulating concentrations of adiponectin in the bloodstream have not been elucidated. Several adiponectin-binding partners, such as AdipoR1/2, have been identified, but do not fully explain the multi-functional and beneficial properties of adiponectin. Recent advances in adiponectin research may resolve these issues. Adiponectin binds to and covers cell surfaces with T-cadherin, a unique glycosylphosphatidylinositol (GPI)-anchored cadherin. The adiponectin/T-cadherin complex enhances exosomal production and release, excreting cell-toxic products from cells, particularly in the vasculature. In this review, we discuss adiponectin and the role of the adiponectin/T-cadherin system in the maintenance of whole body homeostasis and cardiovascular protection.
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Affiliation(s)
- Norikazu Maeda
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, 2-2, Yamada-oka, Suita, Osaka, 565-0871, Japan; Department of Metabolism and Atherosclerosis, Graduate School of Medicine, Osaka University, 2-2, Yamada-oka, Suita, Osaka, 565-0871, Japan.
| | - Tohru Funahashi
- Division of Osaka Health Support Center, Sumitomo Mitsui Banking Corporation, 6-5, Kitahama 4-chome, Chuo-ku, Osaka, Osaka, 541-0041, Japan
| | - Yuji Matsuzawa
- Department of Endocrinology and Metabolism, Sumitomo Hospital, 5-3-20, Nakanoshima, Kita-ku, Osaka, Osaka, 530-0005, Japan
| | - Iichiro Shimomura
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, 2-2, Yamada-oka, Suita, Osaka, 565-0871, Japan
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15
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Zheng H, Qiu L, Su Y, Yi C. Conventional Nanofat and SVF/ADSC-Concentrated Nanofat: A Comparative Study on Improving Photoaging of Nude Mice Skin. Aesthet Surg J 2019; 39:1241-1250. [PMID: 30869120 DOI: 10.1093/asj/sjz066] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Nanofats could improve photoaging. Stromal vascular fraction (SVF) and adipose-derived stem cells (ADSCs) may play pivotal roles. However, SVFs and ADSCs in nanofats processed by conventional methods cannot be enriched. Some researchers have found that after centrifugation, the SVF/ADSC density increases from top to bottom. OBJECTIVES The authors hypothesized that centrifugation can be used to obtain SVF/ADSC-concentrated nanofats that are superior to conventional nanofats in improving the photoaging of skin. METHODS After a photoaging model was successfully established in nude mice, the back of each mouse was divided into 4 areas and randomly injected with conventional nanofat, centrifuged nanofat (either the middle or lower layer of centrifuged nanofat), or normal saline. Wrinkles, dermis thickness, dermal collagen content, and elastic fiber morphology were measured and compared at weeks 4 and 8. RESULTS Compared with the wrinkles in the physiological saline injection areas, the wrinkles in the areas injected with the 3 nanofats (lower and middle layers of centrifuged nanofat and conventional nanofat) were significantly reduced. All 3 nanofat groups showed increased dermal thickness, increased collagen content, and a more regular distribution of elastic fibers compared with the saline injection areas. CONCLUSIONS The study established the efficacy of nanofats in improving photoaging by reducing wrinkles and increasing the thickness of dermal collagen, making nanofats a promising novel treatment for photoaging. The SVF/ADSC-concentrated nanofats exhibited the most improvement.
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Affiliation(s)
- Hui Zheng
- Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, China
| | - Lihong Qiu
- Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, China
| | - Yingjun Su
- Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, China
| | - Chenggang Yi
- Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, China
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16
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Idrizaj E, Garella R, Squecco R, Baccari MC. Adipocytes-released Peptides Involved in the Control of Gastrointestinal Motility. Curr Protein Pept Sci 2019; 20:614-629. [PMID: 30663565 DOI: 10.2174/1389203720666190121115356] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2018] [Revised: 01/07/2019] [Accepted: 01/09/2019] [Indexed: 12/18/2022]
Abstract
The present review focuses on adipocytes-released peptides known to be involved in the control of gastrointestinal motility, acting both centrally and peripherally. Thus, four peptides have been taken into account: leptin, adiponectin, nesfatin-1, and apelin. The discussion of the related physiological or pathophysiological roles, based on the most recent findings, is intended to underlie the close interactions among adipose tissue, central nervous system, and gastrointestinal tract. The better understanding of this complex network, as gastrointestinal motor responses represent peripheral signals involved in the regulation of food intake through the gut-brain axis, may also furnish a cue for the development of either novel therapeutic approaches in the treatment of obesity and eating disorders or potential diagnostic tools.
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Affiliation(s)
- Eglantina Idrizaj
- Department of Experimental and Clinical Medicine, Section of Physiological Sciences, University of Florence, Florence, Italy
| | - Rachele Garella
- Department of Experimental and Clinical Medicine, Section of Physiological Sciences, University of Florence, Florence, Italy
| | - Roberta Squecco
- Department of Experimental and Clinical Medicine, Section of Physiological Sciences, University of Florence, Florence, Italy
| | - Maria Caterina Baccari
- Department of Experimental and Clinical Medicine, Section of Physiological Sciences, University of Florence, Florence, Italy
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17
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Nishizawa H, Shimomura I. Population Approaches Targeting Metabolic Syndrome Focusing on Japanese Trials. Nutrients 2019; 11:nu11061430. [PMID: 31242621 PMCID: PMC6627423 DOI: 10.3390/nu11061430] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Revised: 06/21/2019] [Accepted: 06/23/2019] [Indexed: 12/02/2022] Open
Abstract
The clinical importance of assessment of metabolic syndrome lies in the selection of individuals with multiple risk factors based on visceral fat accumulation, and helping them to reduce visceral fat. Behavioral modification by population approach is important, which adds support to the personal approach. The complexity of visceral fat accumulation requires multicomponent and multilevel intervention. Preparation of food and physical environments could be useful strategies for city planners. Furthermore, actions on various frameworks, including organizational, community, and policy levels, have been recently reported. There are universal public health screening programs and post-screening health educational systems in Japan, and diseases management programs in Germany. Understanding one’s own health status is important for motivation for lifestyle modification. The U.S. Preventive Services Task Force recommends that primary care practitioners screen all adults for obesity and offer behavioral interventions and intensive counseling. Established evidence-based guidelines for behavioral counseling are needed within the primary care setting.
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Affiliation(s)
- Hitoshi Nishizawa
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, 2-2-B5, Yamada-oka, Suita, Osaka 565-0871, Japan.
| | - Iichiro Shimomura
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, 2-2-B5, Yamada-oka, Suita, Osaka 565-0871, Japan.
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18
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Zhao L, Zong W, Zhang H, Liu R. Kidney Toxicity and Response of Selenium Containing Protein-glutathione Peroxidase (Gpx3) to CdTe QDs on Different Levels. Toxicol Sci 2018; 168:201-208. [DOI: 10.1093/toxsci/kfy297] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
- Lining Zhao
- *School of Environmental Science and Engineering, Shandong University, China-America CRC for Environment & Health, Shandong Province, Qingdao, Shandong 266237, P. R. China
| | - Wansong Zong
- College of Population, Resources and Environment, Shandong Normal University, Jinan 250014, P. R. China
| | - Hao Zhang
- Laboratory of Immunology for Environment and Health, Shandong Analysis and Test Center, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250014, China
- Hubei Provincial Key Laboratory of Occurrence and Intervention of Rheumatic Diseases, Affiliated Hospital of Hubei University for Nationalities, Enshi 445000, China
| | - Rutao Liu
- *School of Environmental Science and Engineering, Shandong University, China-America CRC for Environment & Health, Shandong Province, Qingdao, Shandong 266237, P. R. China
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19
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Suárez-Vega A, Arranz JJ, Pérez V, de la Fuente LF, Mateo J, Gutiérrez-Gil B. Early adipose deposits in sheep: comparative analysis of the perirenal fat transcriptome of Assaf and Churra suckling lambs. Anim Genet 2018; 49:605-617. [PMID: 30311245 DOI: 10.1111/age.12725] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/09/2018] [Indexed: 11/28/2022]
Abstract
Adipose deposits influence the quality of ruminant carcasses, and in suckling lambs, internal types of adipose deposits represent a notable proportion of total fat. The aim of this study was to perform a comparative analysis of the perirenal fat transcriptomes of suckling lambs from two breeds with different growth and carcass characteristics. The perirenal fat tissue from 14 suckling lambs (Assaf, n = 8; Churra, n = 6) was used for the RNA-seq analysis. The functional enrichment analysis of the 670 highly expressed genes (>150 fragments per kilobase of exon per million fragments mapped) in the perirenal fat transcriptome of both breeds revealed that the majority of these genes were involved in energy processes. The expression of the UCP1 gene, a classical biomarker of brown fat, and the presence of multilocular adipocytes in the two breeds supported the presence of brown fat at the transition stage towards white fat tissue. The differential expression analysis performed identified 373 differentially expressed genes (DEGs) between the two compared breeds. Brown/white fat gene biomarkers were not included in the list of DEGs. In Assaf lambs, DEGs were enriched in Gene Ontology (GO) biological processes related to fatty-acid oxidation, whereas in Churra lambs, the majority of the significantly enriched GO terms were related to cholesterol synthesis, which suggests that upregulated DEGs in Assaf lambs are implicated in fat burning, whereas the Churra upregulated DEGs are linked to fat accumulation. These results can help to increase knowledge of the genes controlling early fat deposition in ruminants and shed light on fundamental aspects of adipose tissue growth.
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Affiliation(s)
- A Suárez-Vega
- Departamento de Producción Animal, Facultad de Veterinaria, Universidad de León, Campus de Vegazana s/n, León, 24071, Spain
| | - J J Arranz
- Departamento de Producción Animal, Facultad de Veterinaria, Universidad de León, Campus de Vegazana s/n, León, 24071, Spain
| | - V Pérez
- Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad de León, Campus de Vegazana s/n, León, 24071, Spain
| | - L F de la Fuente
- Departamento de Producción Animal, Facultad de Veterinaria, Universidad de León, Campus de Vegazana s/n, León, 24071, Spain
| | - J Mateo
- Departamento de Higiene y Tecnología de los Alimentos, Facultad de Veterinaria, Universidad de León, Campus de Vegazana s/n, León, 24071, Spain
| | - B Gutiérrez-Gil
- Departamento de Producción Animal, Facultad de Veterinaria, Universidad de León, Campus de Vegazana s/n, León, 24071, Spain
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20
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Kugo H, Tanaka H, Moriyama T, Zaima N. Pathological Implication of Adipocytes in AAA Development and the Rupture. Ann Vasc Dis 2018; 11:159-168. [PMID: 30116407 PMCID: PMC6094042 DOI: 10.3400/avd.ra.17-00130] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2017] [Accepted: 02/23/2018] [Indexed: 12/21/2022] Open
Abstract
Abdominal aortic aneurysm (AAA) is a vascular disease that involves the gradual dilation of the abdominal aorta followed by its rupture. AAA is closely associated with weakening of the vascular wall due to oxidative stress, chronic inflammation, and degradation of the extracellular matrix. No effective drug therapy is currently available for preventing aneurysm progression or rupture. Adipocytes in the vascular wall are reportedly closely associated with AAA development and rupture. Fiber degradation in the aneurysm wall is enhanced by increased numbers of adipocytes, and rupture risk may increase as well. Recent studies suggested that appropriate control of adipocytes in the vascular wall may be an important strategy to prevent AAA rupture, and further studies may aid in the establishment of a method for preventing AAA rupture by therapeutic drugs or functional foods. In this review, we summarize adipocyte function and the correlation between AAA and adipocytes.
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Affiliation(s)
- Hirona Kugo
- Department of Applied Biological Chemistry, Graduate School of Agriculture, Kindai University, Nara, Japan
| | - Hiroki Tanaka
- Department of Medical Physiology, Hamamatsu University School of Medicine, Shizuoka, Japan
| | - Tatsuya Moriyama
- Department of Applied Biological Chemistry, Graduate School of Agriculture, Kindai University, Nara, Japan
| | - Nobuhiro Zaima
- Department of Applied Biological Chemistry, Graduate School of Agriculture, Kindai University, Nara, Japan
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21
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Wang X, Shu X, Huo W, Zou L, Li L. Efficacy of protein extracts from medium of Adipose-derived stem cells via microneedles on Asian skin. J COSMET LASER THER 2017; 20:237-244. [PMID: 29283688 DOI: 10.1080/14764172.2017.1400171] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
OBJECTIVES To explore efficacy of protein extracts from medium of Adipose-derived stem cells (ADSCs) via microneedles on Asian skin in a double-blind, split-face, randomized, control study. METHODS Thirty volunteers received the treatment, left-side and right-side of their face were randomly assigned to test side and control side. The protein extracts from medium of ADSCs were applied via microneedles into the test side and ultrapure water was applied into the control side. The only person who knew what was being used by each subject on each side of the face was the therapist. Clinical evaluation including instrument test and self-questionnaire was performed by independent observers before and after the treatment, which lasted for 3 months. RESULTS All subjects completed the study. Compared to ultrapure water, the protein extracts from medium of ADSCs showed a statistically significant improvement for melanin index, skin brightness, gloss, skin roughness, elasticity, and wrinkles (p < 0.05). More than 70% of the participants described that all wrinkles, firmness, elasticity, hydration, whitening, and radiance were strongly improved in the test side. CONCLUSIONS Protein extracts from medium of ADSCs presented anti-aging and whitening efficacy via microneedles on Asian skin without skin adverse side.
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Affiliation(s)
- Xi Wang
- a Department of Dermatology, West China Hospital , Sichuan University , Chengdu , China
| | - Xiaohong Shu
- b Cosmetics Evaluation Center, West China Hospital , Sichuan University , Chengdu , China
| | - Wei Huo
- b Cosmetics Evaluation Center, West China Hospital , Sichuan University , Chengdu , China
| | - Lin Zou
- b Cosmetics Evaluation Center, West China Hospital , Sichuan University , Chengdu , China
| | - Li Li
- a Department of Dermatology, West China Hospital , Sichuan University , Chengdu , China
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Ji L, Wu HT, Qin XY, Lan R. Dissecting carboxypeptidase E: properties, functions and pathophysiological roles in disease. Endocr Connect 2017; 6:R18-R38. [PMID: 28348001 PMCID: PMC5434747 DOI: 10.1530/ec-17-0020] [Citation(s) in RCA: 42] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2017] [Accepted: 03/27/2017] [Indexed: 01/02/2023]
Abstract
Since discovery in 1982, carboxypeptidase E (CPE) has been shown to be involved in the biosynthesis of a wide range of neuropeptides and peptide hormones in endocrine tissues, and in the nervous system. This protein is produced from pro-CPE and exists in soluble and membrane forms. Membrane CPE mediates the targeting of prohormones to the regulated secretory pathway, while soluble CPE acts as an exopeptidase and cleaves C-terminal basic residues from peptide intermediates to generate bioactive peptides. CPE also participates in protein internalization, vesicle transport and regulation of signaling pathways. Therefore, in two types of CPE mutant mice, Cpefat/Cpefat and Cpe knockout, loss of normal CPE leads to a lot of disorders, including diabetes, hyperproinsulinemia, low bone mineral density and deficits in learning and memory. In addition, the potential roles of CPE and ΔN-CPE, an N-terminal truncated form, in tumorigenesis and diagnosis were also addressed. Herein, we focus on dissecting the pathophysiological roles of CPE in the endocrine and nervous systems, and related diseases.
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Affiliation(s)
- Lin Ji
- Department of Cell Biology & Medical GeneticsSchool of Medicine, Shenzhen University, Shenzhen, China
| | - Huan-Tong Wu
- Beijing Engineering Research Center of Food Environment and HealthCollege of Life & Environmental Sciences, Minzu University of China, Beijing, China
| | - Xiao-Yan Qin
- Beijing Engineering Research Center of Food Environment and HealthCollege of Life & Environmental Sciences, Minzu University of China, Beijing, China
| | - Rongfeng Lan
- Department of Cell Biology & Medical GeneticsSchool of Medicine, Shenzhen University, Shenzhen, China
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23
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Park KS, Park KI, Suh HS, Hwang DS, Jang JB, Lee JM. The efficacy and safety of acupuncture on serum leptin levels in obese patients: A systematic review and meta-analysis. Eur J Integr Med 2017. [DOI: 10.1016/j.eujim.2017.03.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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O'Connor EM, Durack E. Osteocalcin: The extra-skeletal role of a vitamin K-dependent protein in glucose metabolism. JOURNAL OF NUTRITION & INTERMEDIARY METABOLISM 2017. [DOI: 10.1016/j.jnim.2017.01.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
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Sano T, Nagayasu S, Suzuki S, Iwashita M, Yamashita A, Shinjo T, Sanui T, Kushiyama A, Kanematsu T, Asano T, Nishimura F. Epicatechin downregulates adipose tissue CCL19 expression and thereby ameliorates diet-induced obesity and insulin resistance. Nutr Metab Cardiovasc Dis 2017; 27:249-259. [PMID: 28062181 DOI: 10.1016/j.numecd.2016.11.008] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2016] [Revised: 11/05/2016] [Accepted: 11/11/2016] [Indexed: 11/20/2022]
Abstract
BACKGROUND AND AIMS Epicatechin (EC) intake has been suggested to be beneficial for the prevention of cardiovascular disorders, and it is well known that adipose tissue inflammation is one of the major risk factors for coronary heart diseases. The purpose of the present study was to determine the in vitro and in vivo effects of EC on adipose tissue inflammation and obesity. METHODS AND RESULTS DNA microarray analysis was performed to evaluate the effects of EC on gene expression in adipocytes co-cultured with bacterial endotoxin-stimulated macrophages. To determine the in vivo effects of the catechin, C57BL/6 mice were fed either a high-fat diet (HFD) or HFD combined with EC, and metabolic changes were observed EC suppressed the expression of many inflammatory genes in the adipocytes co-cultured with endotoxin-stimulated macrophages. Specifically, EC markedly suppressed chemokine (CC motif) ligand 19 (CCL19) expression. The target cell of EC appeared to macrophages. The in vivo study indicated that mice fed the EC-supplemented HFD were protected from diet-induced obesity and insulin resistance. Accordingly, the expression levels of genes associated with inflammation in adipose tissue and in the liver were downregulated in this group of mice. CONCLUSIONS EC exerts beneficial effects for the prevention of adipose tissue inflammation and insulin resistance. Since we previously reported that mice deficient in the CCL19 receptor were protected from diet-induced obesity and insulin resistance, it can be concluded that the beneficial effects of EC could be mediated, at least in part, by marked suppression of CCL19 expression.
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Affiliation(s)
- T Sano
- Section of Periodontology, Kyushu University Faculty of Dental Science, Fukuoka, Japan
| | - S Nagayasu
- Department of Dental Science for Health Promotion, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
| | - S Suzuki
- Department of Dental Science for Health Promotion, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
| | - M Iwashita
- Section of Periodontology, Kyushu University Faculty of Dental Science, Fukuoka, Japan
| | - A Yamashita
- Section of Periodontology, Kyushu University Faculty of Dental Science, Fukuoka, Japan
| | - T Shinjo
- Section of Periodontology, Kyushu University Faculty of Dental Science, Fukuoka, Japan
| | - T Sanui
- Section of Periodontology, Kyushu University Faculty of Dental Science, Fukuoka, Japan
| | - A Kushiyama
- Division of Metabolic Diseases, The Institute for Adult Diseases, Asahi Life Foundation, Tokyo, Japan
| | - T Kanematsu
- Department of Cellular and Molecular Pharmacology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
| | - T Asano
- Department of Biological Chemistry, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
| | - F Nishimura
- Section of Periodontology, Kyushu University Faculty of Dental Science, Fukuoka, Japan.
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Yamamoto H, Nakae H, Uji Y, Maeda K, Tani T, Eguchi Y. Plasma Adiponectin Levels in Acute Liver Failure Patients Treated with Plasma Filtration with Dialysis and Plasma Exchange. Ther Apher Dial 2016; 19:349-54. [PMID: 26386223 DOI: 10.1111/1744-9987.12344] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Plasma filtration with dialysis (PDF) is a blood purification therapy in which simple plasma exchange (PE) is performed using a selective membrane plasma separator while the dialysate flows outside of the hollow fibers. Improvement of hypoadiponectinemia is considered to be a useful therapeutic approach for ameliorating fatal conditions including cardio-metabolic and infectious disease. We investigated the effects of PDF in comparison to PE in terms of plasma adiponectin (APN) changes in patients with acute liver failure. Seventeen patients with liver failure were studied; PDF was performed 55 times and PE 14 times. Plasma APN levels increased significantly after PDF, while decreasing significantly after PE. PDF appears to be among the most useful blood purification therapies in acute liver failure cases in terms of increasing APN levels.
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Affiliation(s)
- Hiroshi Yamamoto
- Department of Surgery, Shiga University of Medical Science, Shiga, Japan
| | - Hajime Nakae
- Department of Emergency and Critical Care Medicine, Akita University School of Medicine, Akita, Japan
| | - Yoshitaka Uji
- Department of Gastroenterological Surgery, Shinkoga Hospital, Fukuoka, Japan
| | - Kazuhisa Maeda
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Tohru Tani
- Department of Surgery, Shiga University of Medical Science, Shiga, Japan
| | - Yutaka Eguchi
- Department of Critical and Intensive Care Medicine, Shiga University of Medical Science, Shiga, Japan
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Tanaka S, Kanazawa I, Notsu M, Sugimoto T. Visceral fat obesity increases serum DPP-4 levels in men with type 2 diabetes mellitus. Diabetes Res Clin Pract 2016; 116:1-6. [PMID: 27321309 DOI: 10.1016/j.diabres.2016.04.027] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2016] [Revised: 04/02/2016] [Accepted: 04/16/2016] [Indexed: 11/18/2022]
Abstract
OBJECTIVE The relationship between serum DPP-4 level and visceral fat mass is still unclear in type 2 diabetes mellitus (T2DM). This study thus aimed to examine the association of visceral fat accumulation and metabolic syndrome with serum DPP-4 levels in T2DM. METHODS Visceral and subcutaneous fat areas were evaluated by performing computed tomography scan in 135 men with T2DM, who had never taken DPP-4 inhibitors or GLP-1 receptor agonists. We investigated the association between serum DPP-4 levels and visceral fat area as well as the presence of metabolic syndrome. RESULTS Multiple regression analysis adjusted for age, duration of T2DM, body mass index, serum creatinine, and HbA1c showed that serum DPP-4 levels were positively associated with visceral fat area (β=0.25, p=0.04), but not subcutaneous fat area (β=-0.18, p=0.13). In logistic regression analyses adjusted for the confounding factors described above, serum DPP-4 levels were positively associated with visceral fat obesity and metabolic syndrome [odds ratio (OR)=1.63, 95% confidence interval (CI)=1.00-2.66 per standard deviation (SD) increase, p=0.04; OR=1.77, 95%CI=1.09-2.88 per SD increase, p=0.02, respectively]. CONCLUSIONS The present study showed that serum DPP-4 level was positively and specifically associated with accumulation of visceral fat and the presence of metabolic syndrome in men with T2DM.
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Affiliation(s)
- Sayuri Tanaka
- Department of Internal Medicine 1, Shimane University Faculty of Medicine, Japan.
| | - Ippei Kanazawa
- Department of Internal Medicine 1, Shimane University Faculty of Medicine, Japan.
| | - Masakazu Notsu
- Department of Internal Medicine 1, Shimane University Faculty of Medicine, Japan.
| | - Toshitsugu Sugimoto
- Department of Internal Medicine 1, Shimane University Faculty of Medicine, Japan.
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Kanazawa I. Osteocalcin as a hormone regulating glucose metabolism. World J Diabetes 2015; 6:1345-1354. [PMID: 26722618 PMCID: PMC4689779 DOI: 10.4239/wjd.v6.i18.1345] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2015] [Revised: 10/23/2015] [Accepted: 12/02/2015] [Indexed: 02/05/2023] Open
Abstract
The number of patients with osteoporosis and diabetes is rapidly increasing all over the world. Bone is recently recognized as an endocrine organ. Accumulating evidence has shown that osteocalcin, which is specifically expressed in osteoblasts and secreted into the circulation, regulates glucose homeostasis by stimulating insulin expression in pancreas and adiponectin expression in adipocytes, resulting in improving glucose intolerance. On the other hand, insulin and adiponectin stimulate osteocalcin expression in osteoblasts, suggesting that positive feedforward loops exist among bone, pancreas, and adipose tissue. In addition, recent studies have shown that osteocalcin enhances insulin sensitivity and the differentiation in muscle, while secreted factors from muscle, myokines, regulate bone metabolism. These findings suggest that bone metabolism and glucose metabolism are associated with each other through the action of osteocalcin. In this review, I describe the role of osteocalcin in the interaction among bone, pancreas, brain, adipose tissue, and muscle.
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Proteomic Analysis of Extracellular Vesicles Released by Adipocytes of Otsuka Long-Evans Tokushima Fatty (OLETF) Rats. Protein J 2015; 34:220-35. [DOI: 10.1007/s10930-015-9616-z] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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Šram M, Vrselja Z, Lekšan I, Ćurić G, Selthofer-Relatić K, Radić R. Epicardial Adipose Tissue Is Nonlinearly Related to Anthropometric Measures and Subcutaneous Adipose Tissue. Int J Endocrinol 2015; 2015:456293. [PMID: 26124828 PMCID: PMC4466489 DOI: 10.1155/2015/456293] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2014] [Accepted: 04/06/2015] [Indexed: 12/28/2022] Open
Abstract
Introduction. Adipose tissue is the largest endocrine organ, composed of subcutaneous (SAT) and visceral adipose tissue (VAT), the latter being highly associated with coronary artery disease (CAD). Expansion of epicardial adipose tissue (EAT) is linked to CAD. One way of assessing the CAD risk is with low-cost anthropometric measures, although they are inaccurate and cannot discriminate between VAT and SAT. The aim of this study is to evaluate (1) the relationship between EAT thickness, SAT thickness and anthropometric measures in a cohort of patients assessed at the cardiology unit and (2) determine predictive power of anthropometric measures and EAT and SAT thickness in establishment of CAD. Methods. Anthropometric measures were obtained from 53 CAD and 42 non-CAD patients. Vascular and structural statuses were obtained with coronarography and echocardiography, as well as measurements of the EAT and SAT thickness. Results. Anthropometric measures showed moderate positive correlation with EAT and SAT thickness. Anthropometric measures and SAT follow nonlinear S curve relationship with EAT. Strong nonlinear power curve relationship was observed between EAT and SAT thinner than 10 mm. Anthropometric measures and EAT and SAT were poor predictors of CAD. Conclusion. Anthropometric measures and SAT have nonlinear relationship with EAT. EAT thickness and anthropometric measures have similar CAD predictive value.
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Affiliation(s)
- Miroslav Šram
- Department of Cardiology, Clinic of Internal Medicine, Osijek University Hospital Centre, 31000 Osijek, Croatia
| | - Zvonimir Vrselja
- Department of Anatomy and Neuroscience, Faculty of Medicine, University of J.J. Strossmayer in Osijek, 31000 Osijek, Croatia
| | - Igor Lekšan
- Department of Cardiac Surgery, Clinic of Surgery, Osijek University Hospital, 31000 Osijek, Croatia
| | - Goran Ćurić
- DNA Laboratory, Department of Chemistry, Biochemistry and Clinical Chemistry, Faculty of Medicine, University of J.J. Strossmayer in Osijek, 31000 Osijek, Croatia
| | - Kristina Selthofer-Relatić
- Department of Cardiology, Clinic of Internal Medicine, Osijek University Hospital Centre, 31000 Osijek, Croatia
- Department of Internal Medicine, Faculty of Medicine, University of J.J. Strossmayer in Osijek, 31000 Osijek, Croatia
- *Kristina Selthofer-Relatić:
| | - Radivoje Radić
- Department of Anatomy and Neuroscience, Faculty of Medicine, University of J.J. Strossmayer in Osijek, 31000 Osijek, Croatia
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Sabour H, Norouzi Javidan A, Latifi S, Shidfar F, Vafa MR, Emami Razavi SH, Larijani B, Heshmat R. Relationship between leptin and adiponectin concentrations in plasma and femoral and spinal bone mineral density in spinal cord-injured individuals. Spine J 2015; 15:1-9. [PMID: 24948038 DOI: 10.1016/j.spinee.2014.06.009] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2014] [Revised: 05/11/2014] [Accepted: 06/09/2014] [Indexed: 02/03/2023]
Abstract
BACKGROUND CONTEXT Previously, the associations between leptin and adiponectin levels with bone mineral density (BMD) have been reported in different populations, and occasionally, controversial results have been demonstrated. Until now, these relationships in spinal cord-injured individuals have not yet been described. PURPOSE We tried to investigate the correlation between leptin and adiponectin concentrations in plasma and BMD in Iranian patients with spinal cord injury (SCI). STUDY DESIGN/SETTING Cross-sectional investigation. PATIENT SAMPLE Referred patients with SCI who did not meet our exclusion criteria such as pregnancy, lactation, amputation, history of diabetes, cancer, endocrinology disease, and use of special medications entered the study. OUTCOME MEASURES Bone mineral density of femoral neck, trochanter, intertrochanteric zone, total hip, and lumbar vertebrae assessed by dual-energy X-ray absorptiometry and serum leptin and adiponectin levels measured by blood sample analysis using immunoassay techniques. METHODS Patient demographic characteristics were measured during face-to-face visits. Injury level and Spinal cord Injury Association (ASIA) score were assessed by clinical examination and were confirmed by imaging aids. Measured levels of leptin and adiponectin and dual-energy X-ray absorptiometry results were analyzed with partial correlation analysis method after adjustment for weight, body mass index (BMI), and age. RESULTS Total of 104 patients (19 females and 85 males) entered this investigation. Higher leptin concentration was significantly associated with higher BMD in femoral neck (p=.006, r=0.73), femoral intertrochanteric zone (p=.001, r=0.83), and hip (p=.001, r=0.81) only in female patients, whereas no such association was detected in male participants after adjusting for BMI and age. Leptin and adiponectin levels were not associated with lumbar spine BMD in both genders. Neither injury level nor ASIA score and plegia type (paraplegia or tetraplegia) influenced on leptin and adiponectin concentrations. CONCLUSIONS We found no association between leptin concentration and BMD in male individuals, whereas a positive correlation between leptin and BMD of femoral neck, intertrochanter, and hip was observed in female patients that shows a sexual polymorphism in this relationship. However, by considering the low number of female participants, these results should be interpreted cautiously. Lumbar spine BMD was associated with neither leptin nor adiponectin level in both genders.
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Affiliation(s)
- Hadis Sabour
- Brain and Spinal Injury Research Center (BASIR), Tehran University of Medical Sciences, Keshavarz Blvd, Tehran, Iran
| | - Abbas Norouzi Javidan
- Brain and Spinal Injury Research Center (BASIR), Tehran University of Medical Sciences, Keshavarz Blvd, Tehran, Iran
| | - Sahar Latifi
- Brain and Spinal Injury Research Center (BASIR), Tehran University of Medical Sciences, Keshavarz Blvd, Tehran, Iran
| | - Farzad Shidfar
- Department of Nutrition, Iran University of Medical Sciences, Hemat Highway, Tehran, Iran
| | - Mohammad Reza Vafa
- Department of Nutrition, Iran University of Medical Sciences, Hemat Highway, Tehran, Iran
| | - Seyed-Hassan Emami Razavi
- Brain and Spinal Injury Research Center (BASIR), Tehran University of Medical Sciences, Keshavarz Blvd, Tehran, Iran
| | - Bagher Larijani
- Endocrinology and Metabolism Research Institute (EMRI), Tehran University of Medical Sciences, Shariati Hospital, North Kargar Avenue, Tehran, Iran
| | - Ramin Heshmat
- Endocrinology and Metabolism Research Institute (EMRI), Tehran University of Medical Sciences, Shariati Hospital, North Kargar Avenue, Tehran, Iran; Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, No. 111, 19th St, North Karegar, Tehran 14579-65597, Iran.
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Al Hannan F, Culligan KG. Human resistin and the RELM of Inflammation in diabesity. Diabetol Metab Syndr 2015; 7:54. [PMID: 26097512 PMCID: PMC4474570 DOI: 10.1186/s13098-015-0050-3] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2015] [Accepted: 06/05/2015] [Indexed: 12/11/2022] Open
Abstract
The initial discovery of resistin and resistin-like molecules (RELMs) in rodents suggested a role for these adipocytokines in molecular linkage of obesity, Type 2 Diabetes mellitus and metabolic syndrome. Since then, it became apparent that the story of resistin and RELMs was very much of mice and men. The putative role of this adipokine family evolved from that of a conveyor of insulin resistance in rodents to instigator of inflammatory processes in humans. Structural dissimilarity, variance in distribution profiles and a lack of corroborating evidence for functional similarities separate the biological functions of resistin in humans from that of rodents. Although present in gross visceral fat deposits in humans, resistin is a component of inflammation, being released from infiltrating white blood cells of the sub-clinical chronic low grade inflammatory response accompanying obesity, rather than from the adipocyte itself. This led researchers to further explore the functions of the resistin family of proteins in inflammatory-related conditions such as atherosclerosis, as well as in cancers such as endometrial and gastric cancers. Although elevated levels of resistin have been found in these conditions, whether it is causative or as a result of these conditions still remains to be determined.
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Affiliation(s)
- Fatima Al Hannan
- />Department of Biomedical Sciences, Royal College of Surgeons in Ireland – Bahrain, Building No. 2441, Road 2835, Busaiteen, Kingdom of Bahrain
| | - Kevin Gerard Culligan
- />Department of Biomedical Sciences, Royal College of Surgeons in Ireland – Bahrain, Building No. 2441, Road 2835, Busaiteen, Kingdom of Bahrain
- />Royal College of Surgeons in Ireland – Bahrain, PO Box 15503, Adliya, Kingdom of Bahrain
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Trayhurn P, Alomar SY. Oxygen deprivation and the cellular response to hypoxia in adipocytes - perspectives on white and brown adipose tissues in obesity. Front Endocrinol (Lausanne) 2015; 6:19. [PMID: 25745415 PMCID: PMC4333869 DOI: 10.3389/fendo.2015.00019] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2015] [Accepted: 02/02/2015] [Indexed: 12/17/2022] Open
Abstract
Relative hypoxia has been shown to develop in white adipose tissue depots of different types of obese mouse (genetic, dietary), and this leads to substantial changes in white adipocyte function. These changes include increased production of inflammation-related adipokines (such as IL-6, leptin, Angptl4, and VEGF), an increase in glucose utilization and lactate production, and the induction of fibrosis and insulin resistance. Whether hypoxia also occurs in brown adipose tissue depots in obesity has been little considered. However, a recent study has reported low pO2 in brown fat of obese mice, this involving mitochondrial loss and dysfunction. We suggest that obesity-linked hypoxia may lead to similar alterations in brown adipocytes as in white fat cells - particularly changes in adipokine production, increased glucose uptake and lactate release, and insulin resistance. This would be expected to compromise thermogenic activity and the role of brown fat in glucose homeostasis and triglyceride clearance, underpinning the development of the metabolic syndrome. Hypoxia-induced augmentation of lactate production may also stimulate the "browning" of white fat depots through recruitment of UCP1 and the development of brite adipocytes.
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Affiliation(s)
- Paul Trayhurn
- Clore Laboratory, Buckingham Institute for Translational Medicine, University of Buckingham, Buckingham, UK
- College of Science, King Saud University, Riyadh, Saudi Arabia
- Obesity Biology Unit, Institute of Ageing and Chronic Diseases, University of Liverpool, Liverpool, UK
- *Correspondence: Paul Trayhurn, Clore Laboratory, Buckingham Institute for Translational Medicine, University of Buckingham, Hunter Street, Buckingham MK18 1EG, UK e-mail:
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Klein N, Neumann J, O'Neil JD, Schneider D. Folding and stability of the aquaglyceroporin GlpF: Implications for human aqua(glycero)porin diseases. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES 2014; 1848:622-33. [PMID: 25462169 DOI: 10.1016/j.bbamem.2014.11.015] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/12/2014] [Revised: 11/12/2014] [Accepted: 11/14/2014] [Indexed: 01/22/2023]
Abstract
Aquaporins are highly selective polytopic transmembrane channel proteins that facilitate the permeation of water across cellular membranes in a large diversity of organisms. Defects in aquaporin function are associated with common diseases, such as nephrogenic diabetes insipidus, congenital cataract and certain types of cancer. In general, aquaporins have a highly conserved structure; from prokaryotes to humans. The conserved structure, together with structural dynamics and the structural framework for substrate selectivity is discussed. The folding pathway of aquaporins has been a topic of several studies in recent years. These studies revealed that a conserved protein structure can be reached by following different folding pathways. Based on the available data, we suggest a complex folding pathway for aquaporins, starting from the insertion of individual helices up to the formation of the tetrameric aquaporin structure. The consequences of some known mutations in human aquaporin-encoding genes, which most likely affect the folding and stability of human aquaporins, are discussed.
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Affiliation(s)
- Noreen Klein
- Department of Pharmacy and Biochemistry, Johannes Gutenberg-University Mainz, 55128 Mainz, Germany
| | - Jennifer Neumann
- Department of Pharmacy and Biochemistry, Johannes Gutenberg-University Mainz, 55128 Mainz, Germany
| | - Joe D O'Neil
- Department of Chemistry, University of Manitoba, Winnipeg, Manitoba R3T 2N2, Canada
| | - Dirk Schneider
- Department of Pharmacy and Biochemistry, Johannes Gutenberg-University Mainz, 55128 Mainz, Germany.
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Yañez-Rivera TG, Baños-Gonzalez MA, Ble-Castillo JL, Torres-Hernandez ME, Torres-Lopez JE, Borrayo-Sanchez G. Relationship between epicardial adipose tissue, coronary artery disease and adiponectin in a Mexican population. Cardiovasc Ultrasound 2014; 12:35. [PMID: 25200587 PMCID: PMC4163040 DOI: 10.1186/1476-7120-12-35] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2014] [Accepted: 08/26/2014] [Indexed: 12/22/2022] Open
Abstract
Background The amount of epicardial adipose tissue (EAT) around the heart has been identified as an independent predictor of coronary artery disease (CAD), potentially through local release of inflammatory cytokines. Ethnic differences have been observed, but no studies have investigated this relationship in the Mexican population. The objective of the present study was to evaluate whether a relationship exist between EAT thickness assessed via echocardiography with CAD and adiponectin levels in a Mexican population. Methods We studied 153 consecutive patients who underwent coronary angiography and transthoracic echocardiography (TTE). EAT thickness on the free wall of the right ventricle was measured at the end of systole from parasternal long and short axis views of three consecutive cardiac cycles. Coronary angiograms were analyzed for the presence, extent and severity of CAD. Serum adiponectin, lipids, glucose, C-reactive protein and fibrinogen were determined. Results EAT thickness was greater in patients with CAD than in those without CAD from both parasternal long (5.39 ± 1.75 mm vs 4.00 ± 1.67 mm p < 0.0001) and short-axis views (5.23 ± 1.67 vs 4.12 ± 1.77, p = 0.001). EAT thickness measured from parasternal long and short-axis showed a statistically significant positive correlation with age (r = 0.354, p < 0.001; r = 0.286, p < 0.001 respectively), and waist circumference (r = 0.189, p = 0.019; r = 0.217, p = 0.007 respectively). A significant negative correlation between EAT thickness from the parasternal long axis with cholesterol-HDL was observed (r = -0.163, p = 0.045). No significant correlation was found between epicardial fat thickness and serum adiponectin or with the severity of CAD. Conclusions EAT thickness was greater in patients with CAD. However, no correlation was observed with the severity of the disease or with serum adiponectin levels. EAT thickness measured by echocardiography might provide additional information for risk assessment and prediction of CAD.
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Affiliation(s)
| | | | - Jorge L Ble-Castillo
- Centro de Investigación y Posgrado, DACS, Universidad Juárez Autónoma de Tabasco (UJAT), Villahermosa, Tabasco, Mexico.
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de Waard EAC, van Geel TACM, Savelberg HHCM, Koster A, Geusens PPMM, van den Bergh JPW. Increased fracture risk in patients with type 2 diabetes mellitus: an overview of the underlying mechanisms and the usefulness of imaging modalities and fracture risk assessment tools. Maturitas 2014; 79:265-74. [PMID: 25192916 DOI: 10.1016/j.maturitas.2014.08.003] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2014] [Accepted: 08/06/2014] [Indexed: 12/11/2022]
Abstract
Type 2 diabetes mellitus has recently been linked to an increased fracture risk. Since bone mass seems to be normal to elevated in patient with type 2 diabetes, the increased fracture risk is thought to be due to both an increased falling frequency and decreased bone quality. The increased falling frequency is mainly a result of complications of the disease such as a retinopathy and polyneuropathy. Bone quality is affected through changes in bone shape, bone micro-architecture, and in material properties such as bone mineralization and the quality of collagen. Commonly used methods for predicting fracture risk such as dual energy X-ray absorptiometry and fracture risk assessment tools are helpful in patients with type 2 diabetes mellitus, but underestimate the absolute fracture risk for a given score. New imaging modalities such as high resolution peripheral quantitative computed tomography are promising for giving insight in the complex etiology underlying the fragility of the diabetic bone, as they can give more insight into the microarchitecture and geometry of the bone. We present an overview of the contributing mechanisms to the increased fracture risk and the usefulness of imaging modalities and risk assessment tools in predicting fracture risk in patients with type 2 diabetes.
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Affiliation(s)
- Ellis A C de Waard
- Maastricht University Medical Centre/NUTRIM, Department of Internal Medicine, Subdivision of Rheumatology, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands.
| | - Tineke A C M van Geel
- Maastricht University/CAPHRI and NUTRIM, Department of Family Medicine, P.O. Box 616, 6200MD Maastricht, The Netherlands
| | - Hans H C M Savelberg
- Maastricht University Medical Centre/NUTRIM, Department of Human Movement Science, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands
| | - Annemarie Koster
- Maastricht University/CAPHRI, Department of Social Medicine, School for Public Health and Primary Care, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands
| | - Piet P M M Geusens
- Maastricht University Medical Centre/CAPHRI, Department of Internal Medicine, Subdivision of Rheumatology, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands; University of Hasselt, Biomedical Research Institute, P.O. Box 6, 3590 Diepenbeek, Belgium
| | - Joop P W van den Bergh
- Maastricht University Medical Centre/NUTRIM, Department of Internal Medicine, Subdivision of Rheumatology, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands; University of Hasselt, Biomedical Research Institute, P.O. Box 6, 3590 Diepenbeek, Belgium; VieCuri Medical Centre, Department of Internal Medicine, Subdivision of Endocrinology, P.O. Box 1926, 5900 BX Venlo, The Netherlands
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Mohiti-Ardekani J, Soleymani-Salehabadi H, Owlia MB, Mohiti A. Relationships between serum adipocyte hormones (adiponectin, leptin, resistin), bone mineral density and bone metabolic markers in osteoporosis patients. J Bone Miner Metab 2014; 32:400-4. [PMID: 24052207 DOI: 10.1007/s00774-013-0511-4] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2012] [Accepted: 08/07/2013] [Indexed: 12/21/2022]
Abstract
The purpose of this study was to investigate the relationship between fasting serum leptin, adiponectin and resistin levels and bone mineral density (BMD) in osteoporosis patients and a non-osteoporosis control group. We studied 81 non-diabetic osteoporosis patients (92 % female, 8 % male; mean age 54.5 ± 15.5 years and body mass index [BMI] 28.2 ± 4.6) and 120 non-diabetic individuals with normal BMD as controls (86 % female, 14 % male; mean age 39.7 ± 10.4 years and BMI 28.8 ± 4.4). BMD was studied by dual-energy X-ray absorptiometry from the lumbar spine (L1-L4) and femoral neck and fasting blood samples were taken for biochemical measurement of fasting blood glucose, leptin, adiponectin and resistin. Fasting levels of plasma adiponectin had a significant negative correlation with BMD of the femoral neck and lumbar spine in the osteoporosis group (r = -0.478, P = 0.003, r = -0.513, P = 0.023) but not in the non-osteoporosis group (r = -0.158, P = 0.057, r = -0.23, P = 0.465). Fasting plasma levels of resistin were significantly correlated only with femur BMD in the osteoporosis group, and not significantly correlated with lumbar spine BMD (r = -0.244, P = 0.048 vs r = 0.276, P = 0.56). Leptin did not have a significant correlation with BMD in either the osteoporosis or non-osteoporosis groups (P > 0.05). Adiponectin had a significant negative correlation with BMD of the lumbar spine and femoral neck. The correlation between leptin and resistin are not inconclusive.
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Affiliation(s)
- J Mohiti-Ardekani
- Department of Biochemistry and Molecular Biology, Faculty of Medicine, Shahid Saduoghi University of Medical Science, Yazd, Iran,
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Matsuzawa Y. Obesity and metabolic syndrome: the contribution of visceral fat and adiponectin. ACTA ACUST UNITED AC 2014. [DOI: 10.2217/dmt.14.30] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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Mori T, Koyama Y, Maeda N, Nakamura Y, Fujishima Y, Matsuda K, Funahashi T, Shimada S, Shimomura I. Ultrastructural localization of adiponectin protein in vasculature of normal and atherosclerotic mice. Sci Rep 2014; 4:4895. [PMID: 24809933 PMCID: PMC4013939 DOI: 10.1038/srep04895] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2014] [Accepted: 04/17/2014] [Indexed: 11/25/2022] Open
Abstract
Adiponectin, adipose-specific secretory protein, abundantly circulates in bloodstream and its concentration is around 1000-fold higher than that of other cytokines and hormones. Hypoadiponectinemia is a risk factor for atherosclerosis. There is little or no information on ultrastructural localization of adiponectin in the vasculature. Herein we investigated the localization of vascular adiponectin in the aorta using the immunoelectron microscopic technique. In wild-type (WT) mice, adiponectin was mainly detected on the luminal surface membrane of endothelial cells (ECs) and also found intracellularly in the endocytic vesicles of ECs. In the atherosclerotic lesions of apolipoprotein E-knockout (ApoE-KO) mice, adiponectin was detected in ECs, on the cell surface membrane of synthetic smooth muscle cells, and on the surface of monocytes adherent to ECs. Changes in adiponectin localization within the wall of the aorta may provide novel insight into the pathogenesis of atherosclerosis.
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Affiliation(s)
- Takuya Mori
- 1] Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan 565-0871 [2]
| | - Yoshihisa Koyama
- 1] Department of Neuroscience and Cell Biology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan 565-0871 [2]
| | - Norikazu Maeda
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan 565-0871
| | - Yukiko Nakamura
- Department of Neuroscience and Cell Biology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan 565-0871
| | - Yuya Fujishima
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan 565-0871
| | - Keisuke Matsuda
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan 565-0871
| | - Tohru Funahashi
- 1] Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan 565-0871 [2] Department of Metabolism and Atherosclerosis, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan 565-0871
| | - Shoichi Shimada
- Department of Neuroscience and Cell Biology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan 565-0871
| | - Iichiro Shimomura
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan 565-0871
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Nakatsuji H, Kishida K, Sekimoto R, Komura N, Kihara S, Funahashi T, Shimomura I. Accumulation of adiponectin in inflamed adipose tissues of obese mice. Metabolism 2014; 63:542-53. [PMID: 24467915 DOI: 10.1016/j.metabol.2013.12.012] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2013] [Revised: 11/29/2013] [Accepted: 12/31/2013] [Indexed: 12/20/2022]
Abstract
OBJECTIVE Adipose tissue inflammation plays an important role in the pathogenesis of obesity-associated complications, such as atherosclerosis. Adiponectin secreted from adipocytes has various beneficial effects including anti-inflammatory effect. Obesity often presents with hypoadiponectinemia. However, the mechanism and adiponectin movement in obesity remain uncharacterized. Here we investigated tissue distribution of adiponectin protein in lean and obese mice. METHODS Adiponectin protein levels were evaluated by enzyme-linked immunosorbent assay and western blotting. Adipose tissues were fractionated into mature adipocyte fraction (MAF) and stromal vascular fraction (SVF). RESULTS Adiponectin protein was detected not only in MAF but also in SVF, which lacks adiponectin mRNA expression, of adipose tissue remarkably. SVF adiponectin protein level was higher in obese mice than in lean mice. The mechanism of adiponectin accumulation was investigated in adiponectin-deficient (APN-KO) mice after injection of plasma from wild-type mice. These mice showed accumulation of exogenous adiponectin, which derived from wild type mice, in adipose tissues, and the adiponectin was more observed in SVF of diet induced obese APN-KO mice than lean APN-KO mice. Among the adiponectin binding proteins, T-cadherin mRNA and protein levels in SVF of obese mice were remarkably higher than in lean mice. Oxidative stress levels were also significantly higher in SVF of obese mice than lean mice. Mechanistically, H2O2 up-regulated T-cadherin mRNA level in murine macrophages. CONCLUSIONS The results demonstrated adiponectin targets to adipose SVF of obese mice. These findings should shed a new light on the pathology of adipose tissue inflammation and hypoadiponectinemia of obesity.
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Affiliation(s)
- Hideaki Nakatsuji
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Ken Kishida
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
| | - Ryohei Sekimoto
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Noriyuki Komura
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Shinji Kihara
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Tohru Funahashi
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan; Department of Metabolism and Atherosclerosis, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Iichiro Shimomura
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan
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Nakatsuji H, Kishida K, Sekimoto R, Funahashi T, Shimomura I. Tracing the movement of adiponectin in a parabiosis model of wild-type and adiponectin-knockout mice. FEBS Open Bio 2014; 4:276-82. [PMID: 24918039 PMCID: PMC4048846 DOI: 10.1016/j.fob.2014.03.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2014] [Revised: 03/04/2014] [Accepted: 03/04/2014] [Indexed: 01/08/2023] Open
Abstract
Adiponectin is exclusively synthesized by adipocytes and exhibits anti-diabetic, anti-atherosclerotic and anti-inflammatory properties. Hypoadiponectinemia is associated in obese individuals with insulin resistance and atherosclerosis. However, the mechanisms responsible for hypoadiponectinemia remain unclear. Here, we investigated adiponectin movement using hetero parabiosis model of wild type (WT) and adiponectin-deficient (KO) mice. WT mice were parabiosed with WT mice (WT-WT) or KO mice (WT-KO) and adiponectin levels were measured serially up to 63 days after surgery. In the WT-KO parabiosis model, circulating adiponectin levels of the WT partners decreased rapidly, on the other hand, those of KO partners increased, and then these reached comparable levels each other at day 7. Circulating adiponectin levels decreased further to the detection limit of assay, and remained low up to day 63. However, adiponectin protein was detected in the adipose tissues of not only the WT partner but also WT-KO mice. In the diet-induced obesity model, high adiponectin protein levels were detected in adipose stromal vascular fraction of diet-induced obese KO partner, without changes in its binding proteins. The use of parabiosis experiments shed light on movement of native adiponectin among different tissues such as the state of hypoadiponectinemia in obesity.
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Key Words
- APN, adiponectin
- Adiponectin
- Adipose tissue
- HF/HS, high fat/high sucrose diet
- KO (WT–KO), KO partner of WT–KO
- KO, adiponectin deficient mice
- MAF, mature adipocyte fraction
- NC, normal chow diet
- Obesity
- Parabiosis
- SVF, stromal vascular fraction
- WATmes, mesenteric white adipose tissue
- WATsub, subcutaneous white adipose tissue
- WT (WT–KO), WT partner of WT–KO
- WT (WT–WT), WT partner of WT–WT
- WT, wild type mice
- WT–KO, parabiosis between WT and KO
- WT–WT, parabiosis between WT and WT
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Affiliation(s)
- Hideaki Nakatsuji
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Ken Kishida
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Ryohei Sekimoto
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Tohru Funahashi
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan ; Department of Metabolism and Atherosclerosis, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Iichiro Shimomura
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan
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Inoue K, Maeda N, Mori T, Sekimoto R, Tsushima Y, Matsuda K, Yamaoka M, Suganami T, Nishizawa H, Ogawa Y, Funahashi T, Shimomura I. Possible involvement of Opa-interacting protein 5 in adipose proliferation and obesity. PLoS One 2014; 9:e87661. [PMID: 24516558 PMCID: PMC3916335 DOI: 10.1371/journal.pone.0087661] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2013] [Accepted: 12/27/2013] [Indexed: 12/15/2022] Open
Abstract
Obesity is an epidemic matter increasing risk for cardiovascular diseases and metabolic disorders such as type 2 diabetes. We recently examined the association between visceral fat adiposity and gene expression profile of peripheral blood cells in human subjects. In a series of studies, Opa (Neisseria gonorrhoeae opacity-associated)-interacting protein 5 (OIP5) was nominated as a molecule of unknown function in adipocytes and thus the present study was performed to investigate the role of OIP5 in obesity. Adenovirus overexpressing Oip5 (Ad-Oip5) was generated and infected to 3T3-L1 cells stably expressing Coxsackie-Adenovirus Receptor (CAR-3T3-L1) and to mouse subcutaneous fat. For a knockdown experiment, siRNA against Oip5 (Oip5-siRNA) was introduced into 3T3-L1 cells. Proliferation of adipose cells was measured by BrdU uptake, EdU-staining, and cell count. Significant increase of Oip5 mRNA level was observed in obese white adipose tissues and such increase was detected in both mature adipocytes fraction and stromal vascular cell fraction. Ad-Oip5-infected CAR-3T3-L1 preadipocytes and adipocytes proliferated rapidly, while a significant reduction of proliferation was observed in Oip5-siRNA-introduced 3T3-L1 preadipocytes. Fat weight and number of adipocytes were significantly increased in Ad-Oip5-administered fat tissues. Oip5 promotes proliferation of pre- and mature-adipocytes and contributes adipose hyperplasia. Increase of Oip5 may associate with development of obesity.
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Affiliation(s)
- Kana Inoue
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Norikazu Maeda
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
- * E-mail:
| | - Takuya Mori
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Ryohei Sekimoto
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Yu Tsushima
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Keisuke Matsuda
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Masaya Yamaoka
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Takayoshi Suganami
- Department of Organ Network and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
| | - Hitoshi Nishizawa
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Yoshihiro Ogawa
- Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
| | - Tohru Funahashi
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
- Department of Metabolism and Atherosclerosis, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Iichiro Shimomura
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
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High serum vaspin concentrations in patients with ulcerative colitis. Dig Dis Sci 2014; 59:315-21. [PMID: 24166663 DOI: 10.1007/s10620-013-2905-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2013] [Accepted: 10/03/2013] [Indexed: 12/09/2022]
Abstract
BACKGROUND Adipocytokines are associated with energy homeostasis and mediate various immune responses and inflammatory processes. Vaspin is a novel adipocytokine that is thought to exhibit anti-inflammatory effects. AIM We aimed to evaluate serum vaspin levels in inflammatory bowel disease (IBD) and determine its possible associations with the course and to clarify its intestinal localization. METHODS Serum samples were obtained from patients with Crohn's disease (CD; n = 30) and ulcerative colitis (UC; n = 33) and from healthy volunteers (controls; n = 26). Enzyme-linked immunosorbent assays were performed for all patients. Vaspin immunohistochemical staining was performed for intestines affected with IBD. RESULTS Serum vaspin concentrations were significantly higher in patients with UC than in patients with CD and controls (422.9 ± 361.9 vs. 163.4 ± 116.2 vs. 147.5 ± 89.4 pg/mL, respectively; P < 0.01). There was no difference in the serum vaspin concentrations between the patients with CD and controls. There was also no difference in the serum vaspin concentrations between the patients with active IBD and those with inactive IBD. However, the serum vaspin concentrations of most patients with UC increased after remission induction. Vaspin was expressed in the adipocytes of the mesenteric adipose tissues but not in the epithelial or inflammatory cells of large intestines of the patients with IBD. CONCLUSIONS Serum vaspin concentrations are elevated in patients with UC and increase further after remission induction, suggesting that vaspin may aid the auxiliary diagnosis of UC and may be useful for assessing disease activity in patients.
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Komolka K, Albrecht E, Wimmers K, Michal JJ, Maak S. Molecular heterogeneities of adipose depots - potential effects on adipose-muscle cross-talk in humans, mice and farm animals. J Genomics 2014; 2:31-44. [PMID: 25057322 PMCID: PMC4105427 DOI: 10.7150/jgen.5260] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Adipose tissue is considered as a major endocrine organ that secretes numerous proteins called adipokines. The heterogeneous nature of adipose tissue in different parts of the body suggests respective heterogeneity of proteomes and secretomes. This review consolidates knowledge from recent studies targeting the diversity of different adipose depots affecting the pattern of secreted adipokines and discusses potential consequences for the cross-talk between adipose and skeletal muscle in humans, rodent models and farm animals. Special attention is paid to muscle-associated fat depots like inter- and intramuscular fat that become focus of attention in the context of the rather new notion of skeletal muscle as a major endocrine organ. Understanding the complexity of communication between adipocytes and skeletal muscle cells will allow developing strategies for improvement of human health and for sustainable production of high quality meat.
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Affiliation(s)
- Katrin Komolka
- 1. Research Unit Muscle Biology and Growth, Leibniz-Institute for Farm Animal Biology (FBN), W.-Stahl-Allee 2, D-18196 Dummerstorf, Germany
| | - Elke Albrecht
- 1. Research Unit Muscle Biology and Growth, Leibniz-Institute for Farm Animal Biology (FBN), W.-Stahl-Allee 2, D-18196 Dummerstorf, Germany
| | - Klaus Wimmers
- 2. Research Unit Molecular Biology, Leibniz-Institute for Farm Animal Biology (FBN), W.-Stahl-Allee 2, D-18196 Dummerstorf, Germany
| | - Jennifer J Michal
- 3. Department of Animal Sciences, Washington State University, Pullman, WA 99164, USA
| | - Steffen Maak
- 1. Research Unit Muscle Biology and Growth, Leibniz-Institute for Farm Animal Biology (FBN), W.-Stahl-Allee 2, D-18196 Dummerstorf, Germany
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Funahashi T, Matsuzawa Y. Adiponectin and the cardiometabolic syndrome: an epidemiological perspective. Best Pract Res Clin Endocrinol Metab 2014; 28:93-106. [PMID: 24417949 DOI: 10.1016/j.beem.2013.09.002] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Adiponectin is an adipocyte-derived plasma protein with cardio-vasculo-protective and anti-diabetic properties. Plasma adiponectin levels are low in patients with the cardiometabolic syndrome (a cluster of multiple risk factors based on visceral fat accumulation). Routine measurement of plasma adiponectin may be useful to encourage life-style changes.
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Affiliation(s)
- Tohru Funahashi
- Department of Metabolism and Atherosclerosis, Osaka University Graduate School of Medicine, 2-2 B5 Yamadaoka, Suita, Osaka 565-0871, Japan.
| | - Yuji Matsuzawa
- Sumitomo Hospital, 5-3-20 Nakanoshima, Kita-Ku, Osaka 530-0005, Japan.
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Decreased plasma levels of brain-derived neurotrophic factor and its relationship with obesity and birth weight in obese Japanese children. Obes Res Clin Pract 2014; 8:e63-9. [DOI: 10.1016/j.orcp.2012.07.003] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2012] [Revised: 07/27/2012] [Accepted: 07/31/2012] [Indexed: 12/27/2022]
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Zhang L, Zhou ZQ, Li G, Fu MZ. The effect of deposition Se on the mRNA expression levels of GPxs in goats from a Se-enriched county of China. Biol Trace Elem Res 2013; 156:111-23. [PMID: 24072670 DOI: 10.1007/s12011-013-9830-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2013] [Accepted: 09/16/2013] [Indexed: 01/18/2023]
Abstract
Previous studies revealed that Se was an important regulatory factor for glutathione peroxidase (GPx) genes. However, the relationship between Se concentrations and mRNA expression levels of GPxs were unclear in goats, especially the goats living in natural Se-enriched area. Thus, the aim of this study was to determine the Se concentrations and the mRNA expression levels of GPx-1, GPx-2, GPx-3, and GPx-4 in goats from Ziyang County (ZY-H and ZY-L goats) and Baoji City (BJ-P goats), which were Se-rich region and Se-poor region in China, respectively. Atomic fluorescence spectrometry was used as an essential method to determine the Se concentrations in heart, liver, spleen, lung, kidney, longissimus, biceps femoris, and serum, and the gene expressions were quantified in mRNA samples extracted from the above tissues by real-time quantitative reverse transcription-polymerase chain reaction. We found that the Se concentrations in ZY-H and ZY-L goats were higher than that in BJ-P goats significantly (P < 0.05), and the pertinence relations of Se levels between serum and heart, liver, spleen, and kidney were significant (P < 0.05). The mRNA levels of GPx-1 in ZY-H and ZY-L goats were higher than that in BJ-P goats very significantly (P < 0.01) except for longissimus (P < 0.05). Our results indicated a significant trend for GPx-2 in the direction of increasing mRNA levels with increasing Se concentrations in goats but had no statistical significance (P > 0.05) in our experimental conditions. As to GPx-3, its mRNA expression in spleen, lung, and kidney (P < 0.05) were upregulated and were consensual to high Se contents in ZY-H goats, but no significant effects were observed in heart, liver, longissimus, and biceps femoris among our three groups (P > 0.05). The mRNA levels of GPx-4 in heart, liver, lung, and kidney of ZY-H and ZY-L goats were higher than that of BJ-P goats (P < 0.05), and the difference was very significant in lung especially (P < 0.01), but no change in spleen, longissimus, and biceps femoris (P > 0.05). In summary, these data suggested that the goats living in Ziyang County were rich in Se, and the deposition Se played important roles in the mRNA expression of GPx-1, GPx-3, and GPx-4 in certain tissues of goats differentially.
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Affiliation(s)
- Lei Zhang
- College of Animal Science and Technology, Northwest A & F University, Yangling, Xianyang, Shaanxi, 712100, China,
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Tarantino G, Finelli C. Pathogenesis of hepatic steatosis: The link between hypercortisolism and non-alcoholic fatty liver disease. World J Gastroenterol 2013; 19:6735-6743. [PMID: 24187449 PMCID: PMC3812473 DOI: 10.3748/wjg.v19.i40.6735] [Citation(s) in RCA: 61] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2013] [Accepted: 09/17/2013] [Indexed: 02/06/2023] Open
Abstract
Based on the available literature, non alcoholic fatty liver disease or generally speaking, hepatic steatosis, is more frequent among people with diabetes and obesity, and is almost universally present amongst morbidly obese diabetic patients. Non alcoholic fatty liver disease is being increasingly recognized as a common liver condition in the developed world, with non alcoholic steatohepatitis projected to be the leading cause of liver transplantation. Previous data report that only 20% of patients with Cushing’s syndrome have hepatic steatosis. Aiming at clarifying the reasons whereby patients suffering from Cushing’s syndrome - a condition characterized by profound metabolic changes - present low prevalence of hepatic steatosis, the Authors reviewed the current concepts on the link between hypercortisolism and obesity/metabolic syndrome. They hypothesize that this low prevalence of fat accumulation in the liver of patients with Cushing’s syndrome could result from the inhibition of the so-called low-grade chronic-inflammation, mainly mediated by Interleukin 6, due to an excess of cortisol, a hormone characterized by an anti-inflammatory effect. The Cushing’s syndrome, speculatively considered as an in vivo model of the hepatic steatosis, could also help clarify the mechanisms of non alcoholic fatty liver disease.
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