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de Melo Cavalcante RB, Leão LMCSM, Tavares ABW, Lopes KG, Terra C, Salgado AA, Kraemer-Aguiar LG. Visceral adipose tissue, epicardial fat, and hepatic steatosis in polycystic ovary syndrome: a study of ectopic fat stores and metabolic dysfunction. Endocrine 2025; 87:866-874. [PMID: 39425841 DOI: 10.1007/s12020-024-04077-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2024] [Accepted: 10/09/2024] [Indexed: 10/21/2024]
Abstract
PURPOSE In polycystic ovary syndrome (PCOS), ectopic fat accumulation remains debatable. Therefore, intra-abdominal, hepatic, and epicardial fat were compared between PCOS women and body mass index (BMI)-matched controls and their associations with metabolic and hormonal parameters were explored. Furthermore, the performance of echocardiographic epicardial adipose tissue thickness (EATT) and hepatic steatosis measurement using transient elastography-based controlled attenuation parameter (TE-CAP) in screening abdominal visceral adipose tissue (VAT) was originally evaluated. METHODS Women aged 18-39 years with BMI < 35 kg/m² were recruited. PCOS was defined by the Rotterdam criteria. All participants underwent clinical and laboratory exams, dual-energy X-ray absorptiometry (DXA), TE-CAP, and echocardiography. A receiver operating characteristic curve was applied to evaluate the accuracy and optimal cutoff values of TE-CAP and EATT in predicting DXA-measured VAT. RESULTS The study included 35 women with PCOS and 37 controls. PCOS women exhibited higher levels of androgens, insulin resistance (IR) parameters, LDL-cholesterol, triglycerides, VAT, and EATT. VAT correlated with IR and triglycerides, whereas EATT correlated with HDL-cholesterol. In PCOS women aged 18-29, the cutoff values of CAP and EATT for VAT were 198.0 and 3.07, respectively, with CAP showing higher area under the curves (AUC). In PCOS women aged 30-39, the cutoff values were 209.5 and 3.36, respectively, with EATT showing higher AUC. CONCLUSION VAT correlates with more metabolic parameters in PCOS than TE-CAP or EATT. TE-CAP is useful for VAT screening in PCOS patients aged 18-39 years, whereas EATT is effective and outperforms CAP in those aged 30-39 years.
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Affiliation(s)
- Rebeca Bandeira de Melo Cavalcante
- Postgraduate Program in Clinical and Experimental Pathophysiology, Faculty of Medical Sciences, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil
| | | | - Ana Beatriz Winter Tavares
- Postgraduate Program in Clinical and Experimental Pathophysiology, Faculty of Medical Sciences, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil
- Endocrinology, Department of Internal Medicine, Faculty of Medical Sciences, State University of Rio de Janeiro (UERJ), Rio de Janeiro, RJ, Brazil
| | - Karynne Grutter Lopes
- Postgraduate Program in Clinical and Experimental Pathophysiology, Faculty of Medical Sciences, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil
- Obesity Unit (SAI-Ob), Multiuser Clinical Research Center (CePeM), Pedro Ernesto University Hospital, State University of Rio de Janeiro (UERJ), Rio de Janeiro, RJ, Brazil
| | - Carlos Terra
- Gastroenterology/Liver Unit, Department of Internal Medicine, Faculty of Medical Sciences, State University of Rio de Janeiro (UERJ), Rio de Janeiro, RJ, Brazil
| | - Angelo Antunes Salgado
- Cardiology, Department of Medical Specialties, Faculty of Medical Sciences, State University of Rio de Janeiro (UERJ), Rio de Janeiro, RJ, Brazil
| | - Luiz Guilherme Kraemer-Aguiar
- Postgraduate Program in Clinical and Experimental Pathophysiology, Faculty of Medical Sciences, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
- Endocrinology, Department of Internal Medicine, Faculty of Medical Sciences, State University of Rio de Janeiro (UERJ), Rio de Janeiro, RJ, Brazil.
- Obesity Unit (SAI-Ob), Multiuser Clinical Research Center (CePeM), Pedro Ernesto University Hospital, State University of Rio de Janeiro (UERJ), Rio de Janeiro, RJ, Brazil.
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Geng Y, Liu Z, Hu R, Ma W, Wu X, Dong H, Song K, Xu X, Huang Y, Li F, Song Y, Zhang M. Opportunities and challenges: interleukin-22 comprehensively regulates polycystic ovary syndrome from metabolic and immune aspects. J Ovarian Res 2023; 16:149. [PMID: 37525285 PMCID: PMC10388558 DOI: 10.1186/s13048-023-01236-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Accepted: 07/13/2023] [Indexed: 08/02/2023] Open
Abstract
Polycystic ovary syndrome (PCOS) is known as a prevalent but complicated gynecologic disease throughout the reproductive period. Typically, it is characterized by phenotypic manifestations of hyperandrogenism, polycystic ovary morphology, and persistent anovulation. For now, the therapeutic modality of PCOS is still a formidable challenge. Metabolic aberrations and immune challenge of chronic low-grade inflammatory state are significant in PCOS individuals. Recently, interleukin-22 (IL-22) has been shown to be therapeutically effective in immunological dysfunction and metabolic diseases, which suggests a role in the treatment of PCOS. In this review, we outline the potential mechanisms and limitations of IL-22 therapy in PCOS-related metabolic disorders including its regulation of insulin resistance, gut barrier, systemic inflammation, and hepatic steatosis to generate insights into developing novel strategies in clinical practice.
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Affiliation(s)
- Yuli Geng
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, China
| | - Zhuo Liu
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, China
| | - Runan Hu
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, China
| | - Wenwen Ma
- Department of Traditional Chinese Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, China
| | - Xiao Wu
- Department of Traditional Chinese Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, China
| | - Haoxu Dong
- Department of Traditional Chinese Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, China
| | - Kunkun Song
- Department of Traditional Chinese Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, China
| | - Xiaohu Xu
- Department of Traditional Chinese Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, China
| | - Yanjing Huang
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, China
| | - Fan Li
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, China
| | - Yufan Song
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, China.
- Department of Traditional Chinese Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, China.
| | - Mingmin Zhang
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, China.
- Department of Traditional Chinese Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, China.
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Manzano-Nunez R, Santana-Dominguez M, Rivera-Esteban J, Sabiote C, Sena E, Bañares J, Tacke F, Pericàs JM. Non-Alcoholic Fatty Liver Disease in Patients with Polycystic Ovary Syndrome: A Systematic Review, Meta-Analysis, and Meta-Regression. J Clin Med 2023; 12:856. [PMID: 36769504 PMCID: PMC9917911 DOI: 10.3390/jcm12030856] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 01/15/2023] [Accepted: 01/19/2023] [Indexed: 01/25/2023] Open
Abstract
BACKGROUND The metabolic effects of polycystic ovary syndrome (PCOS) may increase the risk of non-alcoholic fatty liver disease (NAFLD). However, the burden of NAFLD in PCOS has not been unequivocally defined. This systematic review (SR), meta-analysis (MA) assessed NAFLD's prevalence, and risk factors in patients with PCOS. METHODS A literature search was performed in MEDLINE, Scopus, and Scielo. First, we performed a MA of proportions to estimate the prevalence of NAFLD in PCOS. Second, we performed meta-analyses of precalculated adjusted odds ratios to examine NAFLD risk factors. Finally, we performed a meta-regression to model how the estimated prevalence changed with changes in prespecified variables. RESULTS We identified 817 articles from the database searches. Thirty-six were included. MA of proportions found a pooled NAFLD prevalence of 43% (95% CI, 35-52%) with high heterogeneity (I2 = 97.2%). BMI, waist circumference, ALT values, HOMA-IR values, free androgen index levels, hyperandrogenism, and triglycerides were associated with significantly higher risk-adjusted odds of NAFLD among patients with PCOS. Meta-regression showed that rises in NAFLD prevalence were mediated through increases in metabolic syndrome prevalence and higher levels of HOMA-IR, free androgen index, and total testosterone. CONCLUSION The prevalence of NAFLD (43%) among PCOS patients is high despite their average young age, with several metabolic and PCOS-specific factors influencing its occurrence. Screening programs may aid in detecting metabolic-associated fatty liver disease and prevent its consequences. Further work is required to establish the burden of liver-related outcomes once NAFLD has progressed in the PCOS population.
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Affiliation(s)
- Ramiro Manzano-Nunez
- Liver Unit, Vall d’Hebron University Hospital, 08035 Barcelona, Spain
- Vall d’Hebron Institute for Research, 08035 Barcelona, Spain
- Faculty of Medicine, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain
| | | | - Jesus Rivera-Esteban
- Liver Unit, Vall d’Hebron University Hospital, 08035 Barcelona, Spain
- Vall d’Hebron Institute for Research, 08035 Barcelona, Spain
- Faculty of Medicine, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain
| | - Clara Sabiote
- Liver Unit, Vall d’Hebron University Hospital, 08035 Barcelona, Spain
- Vall d’Hebron Institute for Research, 08035 Barcelona, Spain
| | - Elena Sena
- Liver Unit, Vall d’Hebron University Hospital, 08035 Barcelona, Spain
- Vall d’Hebron Institute for Research, 08035 Barcelona, Spain
| | - Juan Bañares
- Liver Unit, Vall d’Hebron University Hospital, 08035 Barcelona, Spain
- Vall d’Hebron Institute for Research, 08035 Barcelona, Spain
| | - Frank Tacke
- Department of Hepatology & Gastroenterology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, 10117 Berlin, Germany
| | - Juan M. Pericàs
- Liver Unit, Vall d’Hebron University Hospital, 08035 Barcelona, Spain
- Vall d’Hebron Institute for Research, 08035 Barcelona, Spain
- Centros de Investigación Biomédica en Red, Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain
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The Implication of Mechanistic Approaches and the Role of the Microbiome in Polycystic Ovary Syndrome (PCOS): A Review. Metabolites 2023; 13:metabo13010129. [PMID: 36677054 PMCID: PMC9863528 DOI: 10.3390/metabo13010129] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2022] [Revised: 01/09/2023] [Accepted: 01/10/2023] [Indexed: 01/18/2023] Open
Abstract
As a complex endocrine and metabolic condition, polycystic ovarian syndrome (PCOS) affects women's reproductive health. These common symptoms include hirsutism, hyperandrogenism, ovulatory dysfunction, irregular menstruation, and infertility. No one knows what causes it or how to stop it yet. Alterations in gut microbiota composition and disruptions in secondary bile acid production appear to play a causative role in developing PCOS. PCOS pathophysiology and phenotypes are tightly related to both enteric and vaginal bacteria. Patients with PCOS exhibit changed microbiome compositions and decreased microbial diversity. Intestinal microorganisms also alter PCOS patient phenotypes by upregulating or downregulating hormone release, gut-brain mediators, and metabolite synthesis. The human body's gut microbiota, also known as the "second genome," can interact with the environment to improve metabolic and immunological function. Inflammation is connected to PCOS and may be caused by dysbiosis in the gut microbiome. This review sheds light on the recently discovered connections between gut microbiota and insulin resistance (IR) and the potential mechanisms of PCOS. This study also describes metabolomic studies to obtain a clear view of PCOS and ways to tackle it.
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Roy S, Abudu A, Salinas I, Sinha N, Cline-Fedewa H, Yaw AM, Qi W, Lydic TA, Takahashi DL, Hennebold JD, Hoffmann HM, Wang J, Sen A. Androgen-mediated Perturbation of the Hepatic Circadian System Through Epigenetic Modulation Promotes NAFLD in PCOS Mice. Endocrinology 2022; 163:bqac127. [PMID: 35933634 PMCID: PMC9419696 DOI: 10.1210/endocr/bqac127] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Indexed: 11/19/2022]
Abstract
In women, excess androgen causes polycystic ovary syndrome (PCOS), a common fertility disorder with comorbid metabolic dysfunctions including diabetes, obesity, and nonalcoholic fatty liver disease. Using a PCOS mouse model, this study shows that chronic high androgen levels cause hepatic steatosis while hepatocyte-specific androgen receptor (AR)-knockout rescues this phenotype. Moreover, through RNA-sequencing and metabolomic studies, we have identified key metabolic genes and pathways affected by hyperandrogenism. Our studies reveal that a large number of metabolic genes are directly regulated by androgens through AR binding to androgen response element sequences on the promoter region of these genes. Interestingly, a number of circadian genes are also differentially regulated by androgens. In vivo and in vitro studies using a circadian reporter [Period2::Luciferase (Per2::LUC)] mouse model demonstrate that androgens can directly disrupt the hepatic timing system, which is a key regulator of liver metabolism. Consequently, studies show that androgens decrease H3K27me3, a gene silencing mark on the promoter of core clock genes, by inhibiting the expression of histone methyltransferase, Ezh2, while inducing the expression of the histone demethylase, JMJD3, which is responsible for adding and removing the H3K27me3 mark, respectively. Finally, we report that under hyperandrogenic conditions, some of the same circadian/metabolic genes that are upregulated in the mouse liver are also elevated in nonhuman primate livers. In summary, these studies not only provide an overall understanding of how hyperandrogenism associated with PCOS affects liver gene expression and metabolism but also offer insight into the underlying mechanisms leading to hepatic steatosis in PCOS.
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Affiliation(s)
- Sambit Roy
- Reproductive and Developmental Sciences Program, Department of Animal Science, Michigan State University, East Lansing, MI, USA
| | - Aierken Abudu
- Reproductive and Developmental Sciences Program, Department of Animal Science, Michigan State University, East Lansing, MI, USA
| | - Irving Salinas
- Reproductive and Developmental Sciences Program, Department of Animal Science, Michigan State University, East Lansing, MI, USA
| | - Niharika Sinha
- Reproductive and Developmental Sciences Program, Department of Animal Science, Michigan State University, East Lansing, MI, USA
| | - Holly Cline-Fedewa
- Reproductive and Developmental Sciences Program, Department of Animal Science, Michigan State University, East Lansing, MI, USA
| | - Alexandra M Yaw
- Reproductive and Developmental Sciences Program, Department of Animal Science, Michigan State University, East Lansing, MI, USA
| | - Wenjie Qi
- Department of Biomedical Engineering, Michigan State University, East Lansing, MI, USA
| | - Todd A Lydic
- Collaborative Mass Spectrometry Core, Department of Physiology, Michigan State University, East Lansing, MI, USA
| | | | - Jon D Hennebold
- Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Beaverton, OR, USA
- Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, OR, USA
| | - Hanne M Hoffmann
- Reproductive and Developmental Sciences Program, Department of Animal Science, Michigan State University, East Lansing, MI, USA
| | - Jianrong Wang
- Department of Computational Mathematics, Science and Engineering, Michigan State University, East Lansing, MI, USA
| | - Aritro Sen
- Reproductive and Developmental Sciences Program, Department of Animal Science, Michigan State University, East Lansing, MI, USA
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Shalimar, Elhence A, Bansal B, Gupta H, Anand A, Singh TP, Goel A. Prevalence of Non-alcoholic Fatty Liver Disease in India: A Systematic Review and Meta-analysis. J Clin Exp Hepatol 2022; 12:818-829. [PMID: 35677499 PMCID: PMC9168741 DOI: 10.1016/j.jceh.2021.11.010] [Citation(s) in RCA: 53] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2021] [Accepted: 11/18/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) contributes to a large proportion of liver disease burden in the world. Several groups have studied the prevalence of NAFLD in the Indian population. AIM A systematic review of the published literature and meta-analysis was carried out to estimate the prevalence of NAFLD in the Indian population. METHODS English language literature published until April 2021 was searched from electronic databases. Original data published in any form which had reported NAFLD prevalence in the Indian population were included. The subgroup analysis of prevalence was done based on the age (adults or children) and risk category, i.e., average-risk group (community population, participants of control arm, unselected participants, hypothyroidic individuals, athletes, aviation crew, and army personnel) and high-risk group (obesity or overweight, diabetes mellitus, coronary artery disease, etc.). The prevalence estimates were pooled using the random-effects model. Heterogeneity was assessed with I2. RESULTS Sixty-two datasets (children 8 and adults 54) from 50 studies were included. The pooled prevalence of NAFLD was estimated from 2903 children and 23,581 adult participants. Among adults, the estimated pooled prevalence was 38.6% (95% CI 32-45.5). The NAFLD prevalence in average-risk and high-risk subgroups was estimated to be 28.1% (95% CI 20.8-36) and 52.8% (95% CI 46.5-59.1), respectively. The estimated NAFLD prevalence was higher in hospital-based data (40.8% [95% CI 32.6-49.3%]) than community-based data (28.2% [95% CI 16.9-41%]). Among children, the estimated pooled prevalence was 35.4% (95% CI 18.2-54.7). The prevalence among non-obese and obese children was 12.4 (95% CI 4.4-23.5) and 63.4 (95% CI 59.4-67.3), respectively. CONCLUSION Available data suggest that approximately one in three adults or children have NAFLD in India.
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Key Words
- ALT, Alanine aminotransferase
- AST, Aspartate aminotransferase
- BMI, Body mass index
- CAD, Coronary artery disease
- CI, Confidence interval
- DM, Diabetes mellitus
- GBD, Global burden of disease
- GDM, Gestational diabetes mellitus
- GDP, Gross domestic product
- HC, Healthy control
- IGT, Impaired glucose tolerance
- NAFLD, Non-alcoholic fatty liver disease
- NASH, Non-alcoholic steatohepatitis
- NPCDCS, National Program for Prevention and Control of Cancer, Diabetes, Cardiovascular Diseases and Stroke
- OSA, Obstructive sleep apnea
- PCOS, Polycystic ovarian syndrome
- UT, Union Territories
- diabetes mellitus
- fatty liver
- metabolic syndrome
- obesity
- steatohepatitis
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Affiliation(s)
- Shalimar
- All India Institute of Medical Sciences, New Delhi, India
| | - Anshuman Elhence
- Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
| | - Bhavik Bansal
- All India Institute of Medical Sciences, New Delhi, India
| | - Hardik Gupta
- All India Institute of Medical Sciences, New Delhi, India
| | - Abhinav Anand
- All India Institute of Medical Sciences, New Delhi, India
| | - Thakur P. Singh
- Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
| | - Amit Goel
- Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
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Chi ZC. Research status and progress of metabolic associated fatty liver disease. Shijie Huaren Xiaohua Zazhi 2022; 30:1-16. [DOI: 10.11569/wcjd.v30.i1.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Metabolic associated fatty liver disease (MAFLD) is a more appropriate general predicate to describe non-alcoholic fatty liver disease. The new definition lists metabolic dysfunction as an important cause of liver disease, demonstrates the high heterogeneity of this condition, and speeds up the transformation path to new treatment. The incidence of extrahepatic complications and related diseases of MAFLD far exceed that of the liver disease itself, which seriously threatens human health. In view of the current insufficient understanding of its severity, and the imperfect understanding of the disease scope, pathogenesis, and diagnosis of extrahepatic complications, especially the lack of effective drug treatment, this paper introduces and reviews the research status and progress of extrahepatic complications of MAFLD.
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Affiliation(s)
- Zhao-Chun Chi
- Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao 266011, Shandong Province, China
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Wang D, He B. Current Perspectives on Nonalcoholic Fatty Liver Disease in Women with Polycystic Ovary Syndrome. Diabetes Metab Syndr Obes 2022; 15:1281-1291. [PMID: 35494531 PMCID: PMC9048954 DOI: 10.2147/dmso.s362424] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Accepted: 03/31/2022] [Indexed: 12/29/2022] Open
Abstract
Polycystic ovary syndrome (PCOS) is one of the most common reproductive, endocrine, and metabolic disorders in premenopausal women. Clinically, PCOS is mainly caused by androgen excess and ovarian dysfunction, manifested by anovulatory menstrual cycles, infertility, and hirsutism. In addition, PCOS increases the risk of insulin resistance, obesity, cardiovascular disease, anxiety and depression, dyslipidemia, and endometrial cancer. Nonalcoholic fatty liver disease (NAFLD) is defined as ≥5% fat accumulation in the liver in the absence of remaining secondary causes and has become one of the most common chronic liver diseases worldwide. The prevalence of NAFLD is significantly higher and more severe in women with PCOS, and its pathogenesis can be associated with various risk factors such as hyperandrogenemia, insulin resistance, obesity, chronic low-grade inflammation, and genetic factors. Although there is no definitive solution for the management of NAFLD in PCOS, some progress has been made. Lifestyle modification should be the basis of management, and drugs to improve metabolism, such as insulin sensitizers and glucagon-like peptide-1 agonists, may show better efficacy. Bariatric surgery may also be a treatment of NAFLD in obese women with PCOS. This paper reviews three aspects of prevalence, risk factors, and management, in order to better understand the current state of research on NAFLD in PCOS, to explore the pathogenesis of NAFLD in PCOS, and to encourage further research on the application of drugs in this field.
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Affiliation(s)
- Dongxu Wang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China
| | - Bing He
- Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China
- Correspondence: Bing He, Department of Endocrinology, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Shenyang, 110004, People’s Republic of China, Tel/Fax +86-24-96615-23111, Email
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Huang J, Huang B, Kong Y, Yang Y, Tian C, Chen L, Liao Y, Ma L. Polycystic ovary syndrome: Identification of novel and hub biomarkers in the autophagy-associated mRNA-miRNA-lncRNA network. Front Endocrinol (Lausanne) 2022; 13:1032064. [PMID: 36523600 PMCID: PMC9745174 DOI: 10.3389/fendo.2022.1032064] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Accepted: 11/14/2022] [Indexed: 12/03/2022] Open
Abstract
INTRODUCTION Polycystic ovary syndrome (PCOS) is a common metabolic and endocrine disorder prevalent among women of reproductive age. Recent studies show that autophagy participated in the pathogenesis of PCOS, including anovulation, hyperandrogenism, and metabolic disturbances. This study was designed to screen autophagy-related genes (ATGs) that may play a pivotal role in PCOS, providing potential biomarkers and identifying new molecular subgroups for therapeutic intervention. METHODS Gene expression profiles of the PCOS and control samples were obtained from the publicly available Gene Expression Omnibus database. The gene lists of ATGs from databases were integrated. Then, the weighted gene co-expression network analysis was conducted to obtain functional modules and construct a multifactorial co-expression network. Gene Ontology and KEGG pathway enrichment analyses were performed for further exploration of ATG's function in the key modules. Differentially expressed ATGs were identified and validated in external datasets with the Limma R package. To provide guidance on PCOS phenotyping, the dysfunction module consists of a co-expression network mapped to PCOS patients. A PCOS-Autophagy-related co-expression network was established using Cytoscape, followed by identifying molecular subgroups using the Limma R package. ps. RNA-sequencing analysis was used to confirm the differential expression of hub ATGs, and the diagnostic value of hub ATGs was assessed by receiver operating characteristic curve analysis. RESULTS Three modules (Brown, Turquoise, and Green) in GSE8157, three modules (Blue, Red, and Green) in GSE43264, and four modules (Blue, Green, Black, and Yellow) in GSE106724 were identified to be PCOS-related by WGCNA analysis. 29 ATGs were found to be the hub genes that strongly correlated with PCOS. These hub ATGs were mainly enriched in autophagy-related functions and pathways such as autophagy, endocytosis, apoptosis, and mTOR signaling pathways. The mRNA-miRNA-lncRNA multifactorial network was successfully constructed. And three new molecular subgroups were identified via the K-means algorithm. DISCUSSION We provide a novel insight into the mechanisms behind autophagy in PCOS. BRCA1, LDLR, MAP1B, hsa-miR-92b-3p, hsa-miR-20b-5p, and NEAT1 might play a considerably important role in PCOS dysfunction. As a result, new potential biomarkers can be evaluated for use in PCOS diagnosis and treatment in the future.
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Falzarano C, Lofton T, Osei-Ntansah A, Oliver T, Southward T, Stewart S, Andrisse S. Nonalcoholic Fatty Liver Disease in Women and Girls With Polycystic Ovary Syndrome. J Clin Endocrinol Metab 2022; 107:258-272. [PMID: 34491336 DOI: 10.1210/clinem/dgab658] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Indexed: 12/15/2022]
Abstract
CONTEXT Nonalcoholic fatty liver disease (NAFLD) describes a spectrum of liver damage due to excessive hepatic lipid accumulation. Recent research has demonstrated a high prevalence of NAFLD in women with polycystic ovary syndrome (PCOS). RESULTS Strong associations independent of body mass index (BMI) have been found between high androgen levels characteristic of PCOS, as well as insulin resistance, and the presence of NAFLD in these women, suggesting that these factors contribute to liver injury more significantly than obesity. Current studies indicate the occurrence of NAFLD in normal weight women with PCOS in addition to the commonly researched women who are overweight and obese. While the majority of studies address NAFLD in adult, premenopausal women (ages 25-40 years), the occurrence of NAFLD in young and adolescent women has gone largely unaddressed. Research in this field lacks diversity; a majority of studies either focus on populations of White women or are missing demographic information entirely. CONCLUSIONS Future studies should include larger, more racially and ethnically inclusive populations and particular attention should be paid to how excess androgens and insulin resistance contribute to the increased risk of NAFLD seen in women with PCOS of varying weights, ages, and ethnicities. OBJECTIVE AND METHODS Here, we review NAFLD in women with PCOS with subsections focused on the impact of hyperandrogenism, BMI, insulin resistance and age. Most notably, we present the most up-to-date racially and ethnically diverse worldwide prevalence of NAFLD in women with PCOS compared with women without PCOS (51.56% vs 29.64%, P < .001, respectively).
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Affiliation(s)
- Claire Falzarano
- Howard University College of Medicine, Physiology and Biophysics, Washington, DC, 20059, USA
| | - Taylor Lofton
- Howard University College of Medicine, Physiology and Biophysics, Washington, DC, 20059, USA
| | - Adjoa Osei-Ntansah
- Howard University College of Medicine, Physiology and Biophysics, Washington, DC, 20059, USA
| | - Trinitee Oliver
- Howard University College of Medicine, Physiology and Biophysics, Washington, DC, 20059, USA
| | - Taylor Southward
- Howard University College of Medicine, Physiology and Biophysics, Washington, DC, 20059, USA
| | - Salim Stewart
- Howard University College of Medicine, Physiology and Biophysics, Washington, DC, 20059, USA
| | - Stanley Andrisse
- Howard University College of Medicine, Physiology and Biophysics, Washington, DC, 20059, USA
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11
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Kumariya S, Ubba V, Jha RK, Gayen JR. Autophagy in ovary and polycystic ovary syndrome: role, dispute and future perspective. Autophagy 2021; 17:2706-2733. [PMID: 34161185 PMCID: PMC8526011 DOI: 10.1080/15548627.2021.1938914] [Citation(s) in RCA: 155] [Impact Index Per Article: 38.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Revised: 05/30/2021] [Accepted: 06/02/2021] [Indexed: 02/05/2023] Open
Abstract
Polycystic ovary syndrome (PCOS) is a unification of endocrine and metabolic disorders and has become immensely prevalent among women of fertile age. The prime organ affected in PCOS is the ovary and its distressed functioning elicits disturbed reproductive outcomes. In the ovary, macroautophagy/autophagy performs a pivotal role in directing the chain of events starting from oocytes origin until its fertilization. Recent discoveries demonstrate a significant role of autophagy in the pathogenesis of PCOS. Defective autophagy in the follicular cells during different stages of follicles is observed in the PCOS ovary. Exploring different autophagy pathways provides a platform for predicting the possible cause of altered ovarian physiology in PCOS. In this review, we have emphasized autophagy's role in governing follicular development under normal circumstances and in PCOS, including significant abnormalities associated with PCOS such as anovulation, hyperandrogenemia, metabolic disturbances, and related abnormality. So far, few studies have linked autophagy and PCOS and propose its essential role in PCOS progression. However, detailed knowledge in this area is lacking. Here we have summarized the latest knowledge related to autophagy associated with PCOS. This review's main objective is to provide a background of autophagy in the ovary, its possible connection with PCOS and suggested a novel proposal for future studies to aid a better understanding of PCOS pathogenesis.Abbreviations: AE: androgen excess; AF: antral follicle; AKT/PKB: AKT serine/threonine kinase; AMH: anti-Mullerian hormone; AMPK: AMP-activated protein kinase; ATG: autophagy-related; BCL2: BCL2 apoptosis regulator; BECN1: beclin 1; BMP: bone morphogenetic protein; CASP3: caspase 3; CL: corpus luteum; CYP17A1/P450C17: cytochrome P450 family 17 subfamily A member 1; CYP19A1: cytochrome P450 family 19 subfamily A member 1; DHEA: dehydroepiandrosterone; EH: endometrial hyperplasia; FF: follicular fluid; FOXO: forkhead box O; FSH: follicle stimulating hormone; GC: granulosa cell; GDF: growth differentiation factor; HA: hyperandrogenemia; HMGB1: high mobility group box 1; IGF1: insulin like growth factor 1; INS: insulin; IR: insulin resistance; LHCGR/LHR: luteinizing hormone/choriogonadotropin receptor; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MAPK/ERK: mitogen-activated protein kinase; MAPK8/JNK: mitogen-activated protein kinase 8; MTOR: mechanistic target of rapamycin kinase; MTORC: mechanistic target of rapamycin complex; NAFLD: nonalcoholic fatty liver disease; NFKB: nuclear factor kappa B; OLR1/LOX-1: oxidized low density lipoprotein receptor 1; oxLDL: oxidized low-density lipoproteins; PA: palmitic acid; PCOS: polycystic ovary syndrome; PF: primary follicle; PGC: primordial germ cell; PI3K: phosphoinositide 3-kinase; PMF: primordial follicle; ROS: reactive oxygen species; RP: resting pool; SIRT1: sirtuin 1; SQSTM1/p62: sequestosome 1; T2DM: type 2 diabetes mellitus; TC: theca cell; TUG1: taurine up-regulated 1.
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Affiliation(s)
- Sanjana Kumariya
- Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute CSIR-Central Drug Research Institute, Lucknow, India
| | - Vaibhave Ubba
- Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow, India
| | - Rajesh K. Jha
- Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow, India
- Academy of Scientific and Innovative Research, Ghaziabad, India
| | - Jiaur R. Gayen
- Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute CSIR-Central Drug Research Institute, Lucknow, India
- Academy of Scientific and Innovative Research, Ghaziabad, India
- Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow, India
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12
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Park JY, Kim WJ, Chung YH, Kim B, Park Y, Park IY, Ko HS. Association between pregravid liver enzyme levels and gestational diabetes in twin pregnancies: a secondary analysis of national cohort study. Sci Rep 2021; 11:18695. [PMID: 34548558 PMCID: PMC8455664 DOI: 10.1038/s41598-021-98180-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Accepted: 08/24/2021] [Indexed: 12/11/2022] Open
Abstract
Multiple pregnancies are prone to gestational diabetes mellitus (GDM). This study investigated the association between pregravid liver enzyme levels and the development of GDM in a twin pregnancy. Women who had the National Health Screening Examination and delivered their twin babies within one year were enrolled. Pregravid liver enzyme levels were divided into high and low level. Risks for developing GDM by high levels of liver enzymes were analyzed, in subgroups by pregravid obesity or metabolic syndrome. Among the 4348 twin pregnancies, 369 women (8.5%) developed GDM not requiring insulin treatment (GDM - IT), and 119 women (2.7%) developed GDM requiring insulin treatment(GDM + IT). High levels of pregravid GGT and ALT were related to risks of GDM + IT not only in women with obesity or metabolic syndrome (odds ratio[OR] 6.348, 95% confidence interval [CI] 2.579-15.624 and OR 6.879, 95% CI 2.232-21.204, respectively), but also in women without obesity (OR 3.05, 95% CI 1.565-5.946) or without metabolic syndrome (OR 3.338, 95% CI 1.86-5.992), compared to in women with low levels of those. However, there were no significant associations in the pregravid ALT and GGT levels and risks for development of GDM - IT, unrelated to pregravid obesity or metabolic syndrome. Therefore, this study suggests that women with high levels of pregravid GGT and ALT need to recognize their increased risk of GDM + IT, regardless of pregravid obesity or MetS, when they get pregnant twin.
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Affiliation(s)
- Jae-Young Park
- Department of Obstetrics and Gynecology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea
| | - Woo Jeng Kim
- Department of Obstetrics and Gynecology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea
| | - Yoo Hyun Chung
- Department of Obstetrics and Gynecology, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Bongseong Kim
- Department of Biostatistics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Yonggyu Park
- Department of Biostatistics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - In Yang Park
- Department of Obstetrics and Gynecology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea
| | - Hyun Sun Ko
- Department of Obstetrics and Gynecology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.
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13
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Salva-Pastor N, López-Sánchez GN, Chávez-Tapia NC, Audifred-Salomón JR, Niebla-Cárdenas D, Topete-Estrada R, Pereznuñez-Zamora H, Vidaltamayo-Ramírez R, Báez-Arellano ME, Uribe M, Nuño-Lámbarri N. Polycystic ovary syndrome with feasible equivalence to overweight as a risk factor for non-alcoholic fatty liver disease development and severity in Mexican population. Ann Hepatol 2021; 19:251-257. [PMID: 32111488 DOI: 10.1016/j.aohep.2020.01.004] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Revised: 01/09/2020] [Accepted: 01/14/2020] [Indexed: 02/06/2023]
Abstract
INTRODUCTION AND OBJECTIVES Polycystic ovary syndrome (PCOS) is the most common endocrinology disorder in women of reproductive age; these patients have a higher risk of suffering from non-alcoholic fatty liver disease (NAFLD). We determine the frequency of NAFLD in Mexican patients with PCOS and matched-controls. PATIENTS AND METHODS Cross-sectional study, with 98 women of 18-44 years old. Rotterdam 2003 criteria integrated PCOS diagnosis. Those with significant alcohol consumption, chronic liver disease, use of steatogenic drugs, and pharmacological PCOS treatment or fertility protocol were excluded. Controls were matched in a 1:1 ratio by age and body mass index (BMI). The presence of NAFLD was determined by transient elastography performed by a single experienced operator. RESULTS A total of 98 female volunteers at reproductive age were recruited. NAFLD denoted markedly higher in patients with than without PCOS at 69.3% vs. 34.6%, respectively. Compared to controls, PCOS patients had a significantly higher risk of NAFLD (OR=4.26, 95% CI 1.83-9.93). Severe steatosis was the most frequent NAFLD stage between women with PCOS and NAFLD. Patients with hyperandrogenism have a significantly higher mean CAP 277.83dB/m than controls without hyperandrogenism 191.57dB/m. NAFLD prevalence was 84.3% in PCOS patients with phenotype A, while in another phenotype, it was 41.1%. CONCLUSIONS PCOS is an independent risk factor for NAFLD development. NAFLD screening needs to be considered in all PCOS patients independently of BMI, except in PCOS patients without hyperandrogenism and BMI<25.
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Affiliation(s)
- Nicolás Salva-Pastor
- Translational Research Unit, Medica Sur Clinical Foundation, Mexico City, Mexico
| | | | - Norberto Carlos Chávez-Tapia
- Translational Research Unit, Obesity and Digestive Diseases Unit, Medica Sur Clinical Foundation, Mexico City, Mexico
| | | | - Danniela Niebla-Cárdenas
- Department of Gynecology and Obstetrics "Dr. Manuel Gea González" General Hospital, Mexico City, Mexico
| | - Rafael Topete-Estrada
- Department of Gynecology and Obstetrics "Dr. Manuel Gea González" General Hospital, Mexico City, Mexico
| | | | | | | | - Misael Uribe
- Translational Research Unit, Obesity and Digestive Diseases Unit, Medica Sur Clinical Foundation, Mexico City, Mexico
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14
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Shengir M, Chen T, Guadagno E, Ramanakumar AV, Ghali P, Deschenes M, Wong P, Krishnamurthy S, Sebastiani G. Non-alcoholic fatty liver disease in premenopausal women with polycystic ovary syndrome: A systematic review and meta-analysis. JGH OPEN 2021; 5:434-445. [PMID: 33860093 PMCID: PMC8035436 DOI: 10.1002/jgh3.12512] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Revised: 01/30/2021] [Accepted: 02/08/2021] [Indexed: 12/13/2022]
Abstract
Background and Aim Non‐alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS) are prevalent conditions sharing common pathogenic factors. We performed a systematic literature review and meta‐analysis aiming to investigate the association between NAFLD and PCOS among premenopausal PCOS patients. Methods Relevant studies were systematically identified from scientific databases until 2019. We calculated pooled odds ratio (OR) using a random‐effect model, and heterogeneity was addressed through I2. Subgroup analyses and meta‐regression for various covariates were performed. Results Of the 1833 studies retrieved, 23 studies with 7148 participants qualified for quantitative synthesis. The pooled result showed that women with PCOS had a 2.5‐fold increase in the risk of NAFLD compared to controls (pooled OR 2.49, 95% confidence interval [CI] 2.20–2.82). In subgroup analyses comparing PCOS to controls, South American/Middle East PCOS patients had a greater risk of NAFLD (OR 3.55, 95% CI 2.27–5.55) compared to their counterpart from Europe (OR 2.22, 95% CI 1.85–2.67) and Asia (OR 2.63, 95% CI 2.20–3.15). Insulin resistance and metabolic syndrome were more frequent in the PCOS group (OR 1.97, 95% CI 1.44–2.71 and OR 3.39, 95% CI 2.42–4.76, respectively). Study quality and body mass index (BMI) were the only covariates that showed a relationship with the outcome in the meta‐regression, with a regression coefficient of −2.219 (95% CI −3.927 to −0.511) and −1.929 (95% CI −3.776 to −0.0826), respectively. Conclusions This meta‐analysis indicates that premenopausal PCOS patients are associated with 2.5‐fold increase in the risk of NAFLD, and BMI seems to be the main cofactor.
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Affiliation(s)
- Mohamed Shengir
- Division of Experimental Medicine McGill University Montreal Quebec Canada
| | - Tianyan Chen
- Department of Medicine McGill University Health Centre Montreal Quebec Canada
| | - Elena Guadagno
- Harvey E. Beardmore Division of Pediatric Surgery The Montreal Children's Hospital, McGill University Health Centre Montreal Quebec Canada
| | | | - Peter Ghali
- Department of Medicine University of Florida Jacksonville Florida USA
| | - Marc Deschenes
- Department of Medicine McGill University Health Centre Montreal Quebec Canada
| | - Philip Wong
- Department of Medicine McGill University Health Centre Montreal Quebec Canada
| | | | - Giada Sebastiani
- Department of Medicine McGill University Health Centre Montreal Quebec Canada
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15
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Li AA, Ahmed A, Kim D. Extrahepatic Manifestations of Nonalcoholic Fatty Liver Disease. Gut Liver 2021; 14:168-178. [PMID: 31195434 PMCID: PMC7096231 DOI: 10.5009/gnl19069] [Citation(s) in RCA: 69] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2019] [Revised: 03/26/2019] [Accepted: 04/05/2019] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and encompasses a spectrum of pathology from simple steatosis to inflammation and significant fibrosis that leads to cirrhosis. NAFLD and its comorbid conditions extend well beyond the liver. It is a multisystemic clinical disease entity with extrahepatic manifestations such as cardiovascular disease, type 2 diabetes, chronic kidney disease, hypothyroidism, polycystic ovarian syndrome, and psoriasis. Indeed, the most common causes of mortality in subjects with NAFLD are cardiovascular disease, followed by malignancies and then liver-related complications as a distant third. This review focuses on several of the key extrahepatic manifestations of NAFLD and areas for future investigation. Clinicians should learn to screen and initiate treatment for these extrahepatic manifestations in a prompt and timely fashion before they progress to end-organ damage.
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Affiliation(s)
- Andrew A Li
- Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Donghee Kim
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
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16
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Investigating the Relationship Between Insulin Resistance and Fatty Liver in a Random Population of Tehran. HEPATITIS MONTHLY 2020. [DOI: 10.5812/hepatmon.102972] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
Background: Insulin resistance can be a predictor of adverse fatty liver disease and health problems. Objectives: The present study aimed to investigate the effect of insulin resistance on fatty liver disease. Methods: This study used the data of 2,160 individuals registered in a cross-sectional study who were randomly selected from among clients of a nutrition clinic in Tehran from April to December 2019. Insulin resistance and beta-cell activity were calculated by the homeostasis model assessment formula. The study outcome was defined as having fatty liver disease. The odds ratio (95% CI) was calculated using logistic regression models. Results: The mean age was 35 (± 9) in healthy subjects and 49 (± 8) in fatty liver disease patients (age range: 16 to 42 years). Nearly 34.5% of the individuals had fatty liver disease. According to the adjusted results of the logistic regression model, the risk of NAFLD was 1.05 (P < 0.001) for one unit increase in fasting insulin and 1.01 (P < 0.001) for one unit increase in 2-h insulin, which indicated the statistically significant relationship of NAFLD with fasting insulin and 2-h insulin. Also, the risk of NAFLD was 1.01 P < 0.001) for one unit increase in FPG, which was statistically significant. Moreover, the adjusted risk of NAFLD was 1.00 (P < 0.001) for one unit increase in 2-h glucose, which was not statistically significant. Finally, the adjusted risk of NAFLD was 1.29 (P < 0.001) for one unit increase in HOMA-IR, which was statistically significant. Conclusions: The findings of the present study demonstrated that insulin resistance could increase the risk of fatty liver disease. Also, each one-unit increase in fasting blood sugar, fasting insulin, and 2-h insulin increased the risk of fatty liver disease. Therefore, the results of this study may be useful for health policymakers to design suitable preventive and therapeutic interventions for those with NAFLD to prevent and control this disease.
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17
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Wang Y, Guo X, Xu W, Cai J, Zhang Y, Wu C, Li S, Sun Y, Liu W, Tao T. Role of Androgen in Liver Fat Content in Women: Metabolically Advantageous or Disadvantageous? Endocr Pract 2020; 26:1003-1016. [PMID: 33471689 DOI: 10.4158/ep-2019-0407] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2019] [Accepted: 04/29/2020] [Indexed: 12/12/2022]
Abstract
OBJECTIVE Androgens have a controversial effect on liver fat content (LFC) in androgen-excess females and androgen-deficient males. Polycystic ovarian syndrome (PCOS) is often associated with hyperandrogenism and nonalcoholic fatty liver disease. The aim of this study was to explore the association between hyperandrogenemia and increased liver fat content in women with PCOS, independent of other metabolic parameters. METHODS This case series study included 501 women with PCOS and 112 aged-matched controls in the outpatient department of a tertiary hospital. Anthropometric measurements, hepatic and renal function, glucose and lipid metabolism parameters, and sex hormones were examined in these women. LFC was measured by quantitative ultrasonography. RESULTS Women with hyperandrogenism (P<.001), an oligomenorrhoea/anovulation phenotype (P = .0064), and a diagnosis of PCOS (P<.001) had higher LFC. Androgen level is an important factor among the 9 independent risk factors of LFC (P = .0239) and may have a dimorphic impact on LFC. In all women, when the free androgen index (FAI) was less than 41.94, LFC increased with the elevated FAI; when the FAI was greater than 41.94, LFC decreased with the elevated FAI (P<.001). In women with PCOS, receiver operating characteristic curve analysis demonstrated that LFC could at least partially predict impaired glucose regulation, impaired lipid metabolism, and insulin resistance (P<.0001 for all). CONCLUSION Androgen level is associated with LFC in dimorphic directions. LFC may be a predictive factor of insulin resistance, impaired glucose regulation, and impaired lipid metabolism in women with PCOS.
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Affiliation(s)
- Yuying Wang
- From the Department of Endocrinology and Metabolism, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Xiaojing Guo
- the Department of Health Statistics, Second Military Medical University, Shanghai, China
| | - Wendi Xu
- From the Department of Endocrinology and Metabolism, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Jie Cai
- From the Department of Endocrinology and Metabolism, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Yi Zhang
- From the Department of Endocrinology and Metabolism, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Chunhua Wu
- the Division of Ultrasonography, Department of Radiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Shengxian Li
- From the Department of Endocrinology and Metabolism, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Yun Sun
- the Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Wei Liu
- From the Department of Endocrinology and Metabolism, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China; the Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China..
| | - Tao Tao
- From the Department of Endocrinology and Metabolism, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
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18
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Sun LF, Yang YL, Xiao TX, Li MX, Zhang JV. Removal of DHT can relieve polycystic ovarian but not metabolic abnormalities in DHT-induced hyperandrogenism in mice. Reprod Fertil Dev 2020; 31:1597-1606. [PMID: 31142430 DOI: 10.1071/rd18459] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2018] [Accepted: 04/24/2019] [Indexed: 12/30/2022] Open
Abstract
Polycystic ovary syndrome (PCOS) is an endocrine disorder with a high prevalence in women of childbearing age. To date, there is no method of efficiently diagnosing PCOS and curing it completely because its pathomechanism remains unclear. Here, we investigated whether metabolic abnormalities maintain the hyperandrogenism and PCOS-like ovaries and whether the symptoms induced by excess androgen are treatable. We ceased the abnormal dihydrotestosterone (DHT) stimulation to determine changes in PCOS-like mice. After ceasing DHT stimulation, the ovarian morphology and gene expression recovered from the DHT-stimulated status. However, after cessation of DHT stimulation, the hypertrophy of adipose tissues and hepatic steatosis were not significantly restored, and fat accumulation-related gene expression and serum metabolic markers in the mice were altered. These findings showed that the reproductive dysfunction was obviously relieved, but because the metabolic abnormalities were not relieved after the cessation of excess androgen for 30 days, it appears that the latter may not maintain the former.
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Affiliation(s)
- Li-Feng Sun
- Research Laboratory for Reproductive Health, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; and University of Chinese Academy of Sciences, Beijing 100049, China
| | - Ya-Li Yang
- Research Laboratory for Reproductive Health, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
| | - Tian-Xia Xiao
- Research Laboratory for Reproductive Health, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
| | - Meng-Xia Li
- Research Laboratory for Reproductive Health, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
| | - Jian V Zhang
- Research Laboratory for Reproductive Health, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; and Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China; and Corresponding author.
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19
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Sarkar M, Suzuki A. Reproductive Health and Nonalcoholic Fatty Liver Disease in Women: Considerations Across the Reproductive Lifespan. Clin Liver Dis (Hoboken) 2020; 15:219-222. [PMID: 32617153 PMCID: PMC7326635 DOI: 10.1002/cld.955] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2019] [Revised: 03/02/2020] [Accepted: 03/06/2020] [Indexed: 02/04/2023] Open
Affiliation(s)
- Monika Sarkar
- Division of GI/HepatologyUniversity of California, San FranciscoSan FranciscoCA
| | - Ayako Suzuki
- Division of GI/HepatologyDuke UniversityDurhamNC
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20
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Chakraborty S, Ganie MA, Masoodi I, Jana M, Gupta N, Sofi NY. Fibroscan as a non-invasive predictor of hepatic steatosis in women with polycystic ovary syndrome. Indian J Med Res 2020; 151:333-341. [PMID: 32461397 PMCID: PMC7371053 DOI: 10.4103/ijmr.ijmr_610_18] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Background & objectives: There is limited data on non-alcoholic fatty liver disease (NAFLD) among Indian women with polycystic ovary syndrome (PCOS), and there are no data on the utility of fibroscan in its assessment. The objective of this study was thus to investigate the frequency of hepatic steatosis in young women with PCOS and evaluate the utility of transient elastography (TE) in its assessment. Methods: Seventy women diagnosed with PCOS and 60 apparently healthy women (controls) were enrolled in this pilot study. These women were evaluated for clinical, biochemical and hormonal parameters, transabdominal ultrasonography, dual-energy X-ray absorptiometry and fibroscan assessing liver stiffness measure (LSM) and controlled attenuation parameter (CAP). Other indices such as liver fat score (LFS), lipid accumulation product (LAP), fibrosis-4 (FIB-4) and aspartate aminotransferase to platelet ratio index, hepatic steatosis index (HIS) scores were also calculated. The main outcome measures were the presence of NAFLD in women with PCOS and its correlation with CAP and LSM on TE. Results: Women with PCOS had higher frequency (38.57 vs. 6.67%) of hepatic steatosis than control women as determined by abdominal sonography. The aminotransferases were higher in PCOS group (14.28 vs. 1.7%, P=0.03) even after adjusting for body mass index implying higher non-alcoholic steatohepatitis among young PCOS patients. PCOS women had significantly higher CAP on TE compared to controls (210 vs. 196). CAP had a significant correlation with LFS, LAP and HIS. Interpretation & conclusions: NAFLD is common in young women with PCOS, and fibroscan using TE may be considered as a promising non-invasive diagnostic modality in its early detection.
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Affiliation(s)
- Semanti Chakraborty
- Department of Endocrinology & Metabolism, All India Institute of Medical Sciences, New Delhi, India
| | - Mohd Ashraf Ganie
- Department of Endocrinology & Metabolism, All India Institute of Medical Sciences, New Delhi, India
| | - Ibrahim Masoodi
- Department of Medicine, Division of Medical Gastroenterology, Yenepoya Medical College, Mangaluru, Karnataka, India
| | - Manisha Jana
- Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India
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- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Nandita Gupta
- Department of Endocrinology & Metabolism, All India Institute of Medical Sciences, New Delhi, India
| | - Nighat Yaseen Sofi
- Department of Endocrinology & Metabolism, All India Institute of Medical Sciences, New Delhi, India
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21
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NAFLD and Extra-Hepatic Comorbidities: Current Evidence on a Multi-Organ Metabolic Syndrome. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2019; 16:ijerph16183415. [PMID: 31540048 PMCID: PMC6765902 DOI: 10.3390/ijerph16183415] [Citation(s) in RCA: 85] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Revised: 09/06/2019] [Accepted: 09/08/2019] [Indexed: 02/06/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide and its incidence is definitely increasing. NAFLD is a metabolic disease with extensive multi-organ involvement, whose extra-hepatic manifestations include type 2 diabetes mellitus, cardiovascular disease, obstructive sleep apnea, chronic kidney disease, osteoporosis, and polycystic ovarian syndrome. Recently, further evidence has given attention to pathological correlations not strictly related to metabolic disease, also incorporating in this broad spectrum of systemic involvement hypothyroidism, psoriasis, male sexual dysfunction, periodontitis, and urolithiasis. The most common cause of mortality in NAFLD is represented by cardiovascular disease, followed by liver-related complications. Therefore, clinicians should learn to screen and initiate treatment for these extra-hepatic manifestations, in order to provide appropriate multidisciplinary assessments and rigorous surveillance. This review evaluates the current evidence regarding extra-hepatic associations of NAFLD, focusing on the pathogenic hypothesis and the clinical implications.
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Harsha Varma S, Tirupati S, Pradeep TVS, Sarathi V, Kumar D. Insulin resistance and hyperandrogenemia independently predict nonalcoholic fatty liver disease in women with polycystic ovary syndrome. Diabetes Metab Syndr 2019; 13:1065-1069. [PMID: 31336445 DOI: 10.1016/j.dsx.2018.12.020] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2018] [Accepted: 12/26/2018] [Indexed: 12/16/2022]
Abstract
AIMS To find the prevalence and predictors of nonalcoholic fatty liver disease (NAFLD) in Asian Indian polycystic ovary syndrome (PCOS) women. MATERIALS AND METHODS This is a prospective, cross-sectional study conducted at a tertiary care hospital from South India. Sixty women fulfilling the Rotterdam (2003) criteria for PCOS were recruited for the study. All participants were evaluated with ultrasound abdomen for fatty liver and additional biochemical investigations including fasting plasma glucose, postprandial plasma glucose, serum insulin, lipid profile and liver function tests. RESULTS The mean age of the study population was 24.06 ± 5.9 (range: 15-39) years. Oligomenorrhea, hirsutism and acne were present in 58 (96.7%), 37 (61.7%) and 33 (55%) women. Mean BMI of the study population was 29.5 ± 5.28 (range: 19.95 to 45.44) kg/m2. Fifty (83.3%) women were obese (BMI: ≥ 25 kg/m2). Twenty-three (38.3%) women with PCOS had NAFLD. Three women each had isolated elevation of alanine transaminase (ALT) and aspartate transaminases (AST) whereas three women had elevation of both. All women with elevated transaminases had NAFLD. By univariate analysis, factors associated with NAFLD were serum total cholesterol, serum insulin, HOMA-IR, hyperandrogenism, ALT and AST. On multiple regression analysis using linear regression, HOMA-IR and hyperandrogenemia were the only significant predictors of NAFLD. CONCLUSION Our study reports NAFLD in more than one third of Asian Indian women with PCOS. In addition to insulin resistance (HOMA-IR), hyperandrogenemia is an independent predictor of NAFLD in women with PCOS.
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Affiliation(s)
- Sree Harsha Varma
- Department of Endocrinology, Narayana Medical College and Hospital, Nellore, 524003, India.
| | - Sunanda Tirupati
- Department of Endocrinology, Narayana Medical College and Hospital, Nellore, 524003, India.
| | - T V S Pradeep
- Department of Endocrinology, Narayana Medical College and Hospital, Nellore, 524003, India.
| | - Vijaya Sarathi
- Department of Endocrinology, Narayana Medical College and Hospital, Nellore, 524003, India.
| | - Dileep Kumar
- Department of Endocrinology, Narayana Medical College and Hospital, Nellore, 524003, India.
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23
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Patel S. Polycystic ovary syndrome (PCOS), an inflammatory, systemic, lifestyle endocrinopathy. J Steroid Biochem Mol Biol 2018; 182:27-36. [PMID: 29678491 DOI: 10.1016/j.jsbmb.2018.04.008] [Citation(s) in RCA: 288] [Impact Index Per Article: 41.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2018] [Revised: 02/03/2018] [Accepted: 04/16/2018] [Indexed: 02/06/2023]
Abstract
Polycystic ovary syndrome (PCOS) is an endocrine disorder, afflicting females of reproductive age. This syndrome leads to infertility, insulin resistance, obesity, and cardiovascular problems, including a litany of other health issues. PCOS is a polygenic, polyfactorial, systemic, inflammatory, dysregulated steroid state, autoimmune disease, manifesting largely due to lifestyle errors. The advent of biochemical tests and ultrasound scanning has enabled the detection of PCOS in the affected females. Subsequently, a huge amount of insight on PCOS has been garnered in recent times. Interventions like oral contraceptive pills, metformin, and hormone therapy have been developed to bypass or reverse the ill effects of PCOS. However, lifestyle correction to prevent aberrant immune activation and to minimize the exposure to inflammatory agents, appears to be the sustainable therapy of PCOS. This holistic review with multiple hypotheses might facilitate to devise better PCOS management approaches.
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Affiliation(s)
- Seema Patel
- Bioinformatics and Medical Informatics Research Center, San Diego State University, Campanile Dr, San Diego, CA, 92182, USA.
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24
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Wu J, Yao XY, Shi RX, Liu SF, Wang XY. A potential link between polycystic ovary syndrome and non-alcoholic fatty liver disease: an update meta-analysis. Reprod Health 2018; 15:77. [PMID: 29747678 PMCID: PMC5946415 DOI: 10.1186/s12978-018-0519-2] [Citation(s) in RCA: 62] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2017] [Accepted: 04/29/2018] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Epidemiological literature regarding the effect of polycystic ovary syndrome (PCOS) as a risk factor for non-alcoholic fatty liver disease (NAFLD) remains inconsistent. Furthermore, it remains debatable whether NAFLD is associated with PCOS as a consequence of shared risk factors or whether PCOS contributes to NAFLD in an independent fashion. Therefore, this meta-analysis was conducted. METHODS This meta-analysis was conducted in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Relevant studies published before May 2017 were identified and retrieved from PubMed and Web of Science databases. The data were extracted, and the pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS A total of 17 studies were included into the present analysis. Compared to the control group, the risk of NAFLD in the PCOS group was higher (OR = 2.25, 95% CI = 1.95-2.60). When stratified by BMI and geographic location, the results indicated that the frequency of NAFLD risk was significantly higher in obese subjects (OR = 3.01, 95% CI = 1.88-4.82), non-obese subjects (OR = 2.07, 95% CI = 1.12-3.85), subjects from Europe (OR = 2.00, 95% CI = 1.58-2.52), subjects from the Asia-Pacific Region, (OR = 2.32, 95% CI = 1.89-2.84) and subjects from America (OR = 2.96, 95% CI = 1.93-4.55). In addition, PCOS patients with hyperandrogenism (HA) had a significantly higher risk of NAFLD, compared with controls (OR = 3.31, 95% CI = 2.58-4.24). However, there was no association between PCOS patients without HA and higher risk of NAFLD (OR = 1.46; 95% CI =0.55-3.87). The results of this meta-analysis should be interpreted with caution due to the small number of observational studies and possible confounding factors. CONCLUSION The meta-analysis results suggest that PCOS is significantly associated with high risk of NAFLD. Although this association was independent of obesity and geographic region, it might be correlated with HA.
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Affiliation(s)
- Jia Wu
- Department of Gynecology, Changzhou No. 2 Hospital, Affiliated with Nanjing Medical University, Changzhou, 213000 China
| | - Xin-Yu Yao
- Department of Gastroenterology, Changzhou No. 2 Hospital, Affiliated with Nanjing Medical University, Changzhou, 213000 China
| | - Ru-Xia Shi
- Department of Gynecology, Changzhou No. 2 Hospital, Affiliated with Nanjing Medical University, Changzhou, 213000 China
| | - Su-Fen Liu
- Department of Gynecology, Changzhou No. 2 Hospital, Affiliated with Nanjing Medical University, Changzhou, 213000 China
| | - Xiao-Yong Wang
- Department of Gastroenterology, Changzhou No. 2 Hospital, Affiliated with Nanjing Medical University, Changzhou, 213000 China
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25
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Wang Y, Zhou W, Wu C, Zhang Y, Lin T, Sun Y, Liu W, Tao T. Circulating osteopontin and its association with liver fat content in non-obese women with polycystic ovary syndrome: a case control study. Reprod Biol Endocrinol 2018; 16:31. [PMID: 29587769 PMCID: PMC5870073 DOI: 10.1186/s12958-018-0331-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2017] [Accepted: 02/06/2018] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Osteopontin (OPN) plays an important role in inflammatory processes and insulin resistance. Polycystic ovary syndrome (PCOS) is a reproductive metabolic disease associated with insulin resistance and metabolic abnormalities, including high levels of liver fat content (LFC). The objective of this study was to explore whether circulating OPN independently contributes to elevated LFC in non-obese PCOS patients. METHODS This study included 61 non-obese PCOS patients and 56 age-matched healthy women from Shanghai, China. After an overnight fast, all participants underwent anthropometric measurements, oral glucose tolerance tests, lipid profile and sex hormone measurements. Quantitative measurement of LFC by ultrasonography was performed. OPN concentrations were measured using ELISA. An independent samples t-test and the Mann-Whitney U test were performed to compare variables between the two groups; one-way ANOVA and Kruskal-Wallis test were performed to compare four subgroups of patients. Correlations were determined by Spearman's correlation tests. Stepwise multiple linear regression analyses were performed to assess for independent contributors. A receiver operating characteristic curve with the maximum Youden index was calculated for the optimal cut-off value. RESULTS In non-obese PCOS women, circulating OPN levels were increased in the subgroups with a higher body mass index (BMI) and free androgen index (FAI), and the LFC levels were increased in the elevated OPN subgroups. Moreover, increased OPN was associated with increased FAI and LFC in PCOS women, and the association between OPN and LFC was independent of triglyceride, HOMA-IR and FAI after adjusting for PCOS status in all participants. OPN combined with FAI and hsCRP may better predict NAFLD than WHR in this study cohort. However, there was no significant difference in circulating OPN levels between non-obese PCOS and normal control women. CONCLUSIONS Increased OPN levels may be related to FAI and elevated LFC in non-obese women with PCOS.
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Affiliation(s)
- Yuying Wang
- Department of Endocrinology and Metabolism, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road, Shanghai, 200127, China
| | - Wei Zhou
- Department of Emergency, South Campus, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Chunhua Wu
- Division of Ultrasonography, Department of Radiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road, Shanghai, 200127, China
| | - Yi Zhang
- Department of Endocrinology and Metabolism, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road, Shanghai, 200127, China
| | - Tzuchun Lin
- Department of Endocrinology and Metabolism, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road, Shanghai, 200127, China
| | - Yun Sun
- Shanghai Key laboratory for Assisted Reproduction and Reproductive Genetics, Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road, Shanghai, 200127, China
| | - Wei Liu
- Department of Endocrinology and Metabolism, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road, Shanghai, 200127, China.
- Shanghai Key laboratory for Assisted Reproduction and Reproductive Genetics, Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road, Shanghai, 200127, China.
| | - Tao Tao
- Department of Endocrinology and Metabolism, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road, Shanghai, 200127, China.
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26
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Rocha ALL, Faria LC, Guimarães TCM, Moreira GV, Cândido AL, Couto CA, Reis FM. Non-alcoholic fatty liver disease in women with polycystic ovary syndrome: systematic review and meta-analysis. J Endocrinol Invest 2017; 40:1279-1288. [PMID: 28612285 DOI: 10.1007/s40618-017-0708-9] [Citation(s) in RCA: 113] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2017] [Accepted: 06/05/2017] [Indexed: 02/06/2023]
Abstract
PURPOSE Non-alcoholic fatty liver disease (NAFLD) is an insidious pathologic condition that can manifest from simple steatosis to steatohepatitis (NASH) with potential progression to cirrhosis. Like the polycystic ovary syndrome (PCOS), NAFLD is associated with obesity, diabetes mellitus, insulin resistance and metabolic syndrome. PCOS women have an increased risk of NAFLD, but it is debatable which features of PCOS, either specific (androgen excess) or unspecific (metabolic derangements) affect the NAFLD risk. METHODS We performed a systematic review and meta-analysis of studies that addressed the association of PCOS and NAFLD. We selected 17 studies published between 2007 and 2017 that included 2734 PCOS patients and 2561 controls of similar age and body mass index (BMI). RESULTS PCOS patients have increased prevalence of NAFLD (odds ratio 2.54, 95% confidence interval 2.19-2.95). PCOS women with hyperandrogenism (classic phenotype) have a higher prevalence of NAFLD compared to women with PCOS without hyperandrogenism, even after correction for confounding variables. Among women with PCOS, those with NAFLD have higher serum total testosterone (mean difference 0.40 nmol/L, 95% CI 0.29-0.50 nmol/L) and free androgen index (mean difference 4.46, 95% CI 3.53-5.39) than those without NAFLD. The studies that used multivariate analysis controlling for age, BMI, triglycerides, and insulin resistance index confirmed that serum androgens are independent predictors of NAFLD in women with PCOS. CONCLUSION The prevalence of NAFLD is increased in women with PCOS and the presence of NAFLD is associated with high serum androgen levels, in addition to obesity and insulin resistance.
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Affiliation(s)
- A L L Rocha
- Department of Obstetrics and Gynecology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - L C Faria
- Department of Internal Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - T C M Guimarães
- Department of Internal Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - G V Moreira
- Department of Obstetrics and Gynecology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - A L Cândido
- Department of Internal Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - C A Couto
- Department of Internal Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - F M Reis
- Department of Obstetrics and Gynecology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
- Division of Human Reproduction, Departments of Obstetrics and Gynecology, Hospital das Clínicas, Universidade Federal de Minas Gerais, Av. Alfredo Balena, 110, 9˚ andar, Belo Horizonte, MG, 30130-100, Brazil.
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27
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Mehrabian F, Jahanmardi R. Nonalcoholic Fatty Liver Disease in a Sample of Iranian Women with Polycystic Ovary Syndrome. Int J Prev Med 2017; 8:79. [PMID: 29114377 PMCID: PMC5651659 DOI: 10.4103/ijpvm.ijpvm_305_16] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2016] [Accepted: 07/09/2017] [Indexed: 01/10/2023] Open
Abstract
Introduction: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women in reproductive age that is associated with insulin resistance (IR) and metabolic abnormalities which are also a part of metabolic syndrome (Met S). This study was aimed to determine the prevalence of nonalcoholic fatty liver disease (NAFLD) women diagnosed with PCOS based on the Rotterdam criteria from January 2013 to June 2014. Methods: In this cross-sectional study, 75 women with PCOS and 75 healthy controls were enrolled. Anthropometric parameters, biochemical and hormonal investigation, were measured in all women. IR was calculated by homeostasis model assessment. Abdominal ultrasonography and biochemical tests were used to determine the NAFLD. Results: The level of triglyceride, cholesterol, low-density lipoprotein, aspartate aminotransferase, alkalin phosphatase, fasting insulin, and homeostatic model assessment index in women with PCOS were significantly higher than women without PCOS. High-density lipoprotein and alanine aminotransferase (ALT) in women with PCOS were significantly lower. The frequency of IR women with or without PCOS was 53.3% and 29.3%, respectively (P = 0.003). The frequency of Met S in women with PCOS was 33.3% and in other was 10.7% (P = 0.001). The prevalence of fatty liver in women with or without PCOS was 38.7% and 18.7%, respectively (0.008). In women with PCOS, body mass index (BMI) (odds ratio [OR] = 4.25; P = 0.046), ALT (OR = 1.62; P = 0.005), fasting insulin (OR = 1.32; P = 0.032), and IR (OR = 58.17; P = 0.025) were associated with a higher fatty liver. Conclusions: NAFLD is frequent in patients with PCOS with combination with other metabolic derangements. BMI, ALT, fasting insulin, and IR are the risk factors for high prevalence of NAFLD in women with PCOS.
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Affiliation(s)
- Ferdous Mehrabian
- Department of Obstetrics and Gynecology, Medical School, University of Medical Sciences, Isfahan, Iran
| | - Roya Jahanmardi
- Department of Obstetrics and Gynecology, Medical School, University of Medical Sciences, Isfahan, Iran
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28
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Macut D, Božić-Antić I, Bjekić-Macut J, Tziomalos K. MANAGEMENT OF ENDOCRINE DISEASE: Polycystic ovary syndrome and nonalcoholic fatty liver disease. Eur J Endocrinol 2017; 177:R145-R158. [PMID: 28694246 DOI: 10.1530/eje-16-1063] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2016] [Revised: 04/26/2017] [Accepted: 05/04/2017] [Indexed: 12/15/2022]
Abstract
Polycystic ovary syndrome (PCOS) is a frequent endocrine disease in women, with a number of metabolic and reproductive consequences. Obesity, insulin resistance (IR) and type 2 diabetes are prominent metabolic characteristics of PCOS and common factors affecting liver function and generating nonalcoholic fatty liver disease (NAFLD). Multiple genes involved in the synthesis of androgens, cytokines and IR, as well as acquired factors, such as endocrine disruptors, could associate the etiopathogenesis of PCOS and NAFLD. Besides the high prevalence of PCOS in general population, NAFLD was shown to be a frequent condition in transition periods, such as adolescence and menopause. Although liver biopsy is considered to be the gold standard for diagnosing liver damage, its routine use in such a prevalent condition as PCOS can be related to a higher rate of complications. Therefore, it is necessary to be able to diagnose NAFLD using simple and reliable surrogate markers. Recently, fatty liver index and NAFLD fatty liver score analyzed in large cohorts of PCOS women have been shown as accurate markers of liver damage in this metabolically vulnerable population. Lifestyle changes are still the mainstay of the management of NAFLD in PCOS, although prospective randomized controlled clinical studies remain a priority in the field. With regard to medications, metformin may be the drug of choice for treating PCOS patients with NAFLD when pharmacologic therapy is considered. Liraglutide use in obese PCOS has shown favorable effects on the predictors of liver fibrosis. In this review, we aim to summarize the influence of the common risk factors and to discuss the diagnostic approaches and management options for NAFLD in patients with PCOS.
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Affiliation(s)
- Djuro Macut
- Clinic of Endocrinology, Diabetes and Metabolic Diseases
| | | | - Jelica Bjekić-Macut
- Department of Endocrinology, CHC Bezanijska Kosa, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Konstantinos Tziomalos
- First Propaedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece
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Kim JJ, Kim D, Yim JY, Kang JH, Han KH, Kim SM, Hwang KR, Ku SY, Suh CS, Kim SH, Choi YM. Polycystic ovary syndrome with hyperandrogenism as a risk factor for non-obese non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2017; 45:1403-1412. [PMID: 28370150 DOI: 10.1111/apt.14058] [Citation(s) in RCA: 60] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2016] [Revised: 12/13/2016] [Accepted: 03/04/2017] [Indexed: 12/13/2022]
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is known to be associated with polycystic ovary syndrome (PCOS). However, most studies investigated the prevalence of NAFLD in obese PCOS patients. AIM To compare the prevalence of non-obese NAFLD in women with or without PCOS, and to assess an independent association between PCOS and NAFLD in a non-obese Asian cohort. METHODS This was a case-control study using a prospective PCOS cohort. After subjects with other potential causes of chronic liver disease were excluded, 275 non-obese women with PCOS and 892 non-obese controls were enrolled. NAFLD was determined by hepatic ultrasonography. Main outcomes were the prevalence of NAFLD on hepatic ultrasonography between non-obese women with or without PCOS, and an independent association between non-obese NAFLD and PCOS. RESULTS Non-obese women with PCOS had a significantly higher prevalence of NAFLD than those without PCOS (5.5% vs. 2.8%, P = 0.027). PCOS was associated with non-obese NAFLD (odds ratio: 2.62, 95% confidence intervals: 1.25-5.48) after adjustment for age and body mass index (BMI). In women with PCOS, the level of androgenicity represented by free testosterone or free androgen index was associated with NAFLD after adjustment for age, BMI, lipid profile, insulin resistance or glycaemic status. CONCLUSIONS Non-obese NAFLD is more prevalent in women with polycystic ovary syndrome than in those without. In non-obese patients with polycystic ovary syndrome, hyperandrogenemia may be an independent risk factor for non-obese NAFLD.
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Affiliation(s)
- J J Kim
- Department of Obstetrics and Gynecology, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Korea
- The Institute of Reproductive Medicine and Population, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea
| | - D Kim
- Department of Internal Medicine, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Korea
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - J Y Yim
- Department of Internal Medicine, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Korea
| | - J H Kang
- Department of Radiology, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Korea
| | - K H Han
- Department of Obstetrics and Gynecology, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Korea
| | - S M Kim
- Department of Obstetrics and Gynecology, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Korea
| | - K R Hwang
- Department of Obstetrics and Gynecology, Seoul Municipal Boramae Hospital, Seoul, Korea
| | - S Y Ku
- The Institute of Reproductive Medicine and Population, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
| | - C S Suh
- The Institute of Reproductive Medicine and Population, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
| | - S H Kim
- The Institute of Reproductive Medicine and Population, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
| | - Y M Choi
- The Institute of Reproductive Medicine and Population, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
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Metabolic consequences of obesity and insulin resistance in polycystic ovary syndrome: diagnostic and methodological challenges. Nutr Res Rev 2017; 30:97-105. [PMID: 28222828 DOI: 10.1017/s0954422416000287] [Citation(s) in RCA: 90] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Women with polycystic ovary syndrome (PCOS) have a considerable risk of metabolic dysfunction. This review aims to present contemporary knowledge on obesity, insulin resistance and PCOS with emphasis on the diagnostic and methodological challenges encountered in research and clinical practice. Variable diagnostic criteria for PCOS and associated phenotypes are frequently published. Targeted searches were conducted to identify all available data concerning the association of obesity and insulin resistance with PCOS up to September 2016. Articles were considered if they were peer reviewed, in English and included women with PCOS. Obesity is more prevalent in women with PCOS, but studies rarely reported accurate assessments of adiposity, nor split the study population by PCOS phenotypes. Many women with PCOS have insulin resistance, though there is considerable variation reported in part due to not distinguishing subgroups known to have an impact on insulin resistance as well as limited methodology to measure insulin resistance. Inflammatory markers are positively correlated with androgen levels, but detailed interactions need to be identified. Weight management is the primary therapy; specific advice to reduce the glycaemic load of the diet and reduce the intake of pro-inflammatory SFA and advanced glycation endproducts have provided promising results. It is important that women with PCOS are educated about their increased risk of metabolic complications in order to make timely and appropriate lifestyle modifications. Furthermore, well-designed robust studies are needed to evaluate the mechanisms behind the improvements observed with dietary interventions.
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31
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Abstract
Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting reproductive-age women. PCOS causes hyperandrogenism and anovulation and increases the risk of multiple health conditions including infertility, diabetes mellitus, and cardiovascular disease. This article outlines current recommendations for diagnostic testing, treatment options, and holistic care of the woman with PCOS.
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32
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Targher G, Rossini M, Lonardo A. Evidence that non-alcoholic fatty liver disease and polycystic ovary syndrome are associated by necessity rather than chance: a novel hepato-ovarian axis? Endocrine 2016; 51:211-21. [PMID: 26024975 DOI: 10.1007/s12020-015-0640-8] [Citation(s) in RCA: 64] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2015] [Accepted: 05/22/2015] [Indexed: 02/06/2023]
Abstract
Increasing evidence suggests that non-alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS) are associated with obesity, insulin resistance, metabolic syndrome, cardiovascular disease, cirrhosis, and liver tumors. On these grounds, we have hypothesized that NAFLD and PCOS occur more frequently than expected by chance alone. We have tested this hypothesis by reviewing the clinical and biological evidence that supports a significant association between NAFLD and PCOS. PubMed was extensively searched for articles published through March 2015 using the keywords "nonalcoholic fatty liver disease" or "fatty liver" combined with "PCOS." Several cross-sectional and case-control studies have consistently demonstrated that the prevalence of NAFLD is remarkably increased in young women with PCOS, independent of overweight/obesity and other coexisting metabolic syndrome features, and that these women are more likely to have the more severe forms of NAFLD (non-alcoholic steatohepatitis, advanced fibrosis, and cirrhosis). Accumulating evidence suggests that NAFLD, especially its necro-inflammatory form, may exacerbate hepatic and systemic insulin resistance and releases multiple pro-inflammatory, pro-coagulant, and pro-fibrogenic mediators that may play important roles in the pathophysiology of PCOS. These findings call for more active and systematic search for NAFLD among women with PCOS. Conversely, gastroenterologists/hepatologists need to be aware of the presence of PCOS among female patients with NAFLD and compatible clinical features. Finally, all these patients should undergo regular follow-up not only for liver-related complications but also for cardio-metabolic diseases.
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Affiliation(s)
- Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Piazzale Stefani, 1, 37126, Verona, Italy.
| | - Maurizio Rossini
- Section of Rheumatology, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Amedeo Lonardo
- Outpatient Liver Clinic and Division of Internal Medicine - Department of Biomedical, Metabolic and Neural Sciences, NOCSAE, Baggiovara, Azienda USL, University of Modena and Reggio Emilia, Modena, Italy
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33
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Palioura E, Diamanti-Kandarakis E. Polycystic ovary syndrome (PCOS) and endocrine disrupting chemicals (EDCs). Rev Endocr Metab Disord 2015; 16:365-71. [PMID: 26825073 DOI: 10.1007/s11154-016-9326-7] [Citation(s) in RCA: 89] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Polycystic ovary syndrome (PCOS) is a heterogeneous disorder of unclear etiopathogenesis that is likely to involve genetic and environmental components synergistically contributing to its phenotypic expression. Endocrine disrupting chemicals (EDCs) and in particular Bisphenol A (BPA) represent a group of widespread pollutants intensively investigated as possible environmental contributors to PCOS pathogenesis. Substantial evidence from in vitro and animal studies incriminates endocrine disruptors in the induction of reproductive and metabolic aberrations resembling PCOS characteristics. In humans, elevated BPA concentrations are observed in adolescents and adult PCOS women compared to reproductively healthy ones and are positively correlated with hyperandrogenemia, implying a potential role of the chemical in PCOS pathophysiology, although a causal interference cannot yet be established. It is plausible that developmental exposure to specific EDCs could permanently alter neuroendocrine, reproductive and metabolic regulation favoring PCOS development in genetically predisposed individuals or it could accelerate and/or exacerbate the natural course of the syndrome throughout life cycle exposure.
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Affiliation(s)
- Eleni Palioura
- Department of Endocrinology and Center of Excellence in Diabetes, Euroclinic Athens, Athens, Greece
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Ramezani-Binabaj M, Motalebi M, Karimi-sari H, Rezaee-Zavareh MS, Alavian SM. Are women with polycystic ovarian syndrome at a high risk of non-alcoholic Fatty liver disease; a meta-analysis. HEPATITIS MONTHLY 2014; 14:e23235. [PMID: 25598791 PMCID: PMC4286712 DOI: 10.5812/hepatmon.23235] [Citation(s) in RCA: 60] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
CONTEXT Insulin resistance is a hallmark of metabolic syndrome (MS). It has been proposed that both polycystic ovarian syndrome (PCOS) and nonalcoholic fatty liver disease (NAFLD) are correlated with Insulin resistance. Therefore, PCOS and NAFLD can be attributed with insulin resistance and therefore MS. The aim of this meta-analysis was to determine whether PCOS patients are at a high risk of NAFLD. EVIDENCE ACQUISITION Google scholar, Scopus, ISI Web of Science, Embase, MEDLINE, and some Iranian databases such as scientific information database (SID), IranMedex, and MagIran were searched to identify relevant studies. We included all papers regardless of their language from January 1985 to June 2013. By using data on prevalence of NAFLD in patients with and without PCOS, odds ratio (OR) with 95% confidence intervals (CIs) were calculated in each study. Chi-squared test was used to assess heterogeneity between studies. RESULTS We finally included seven eligible studies. According to chi-squared test, there was a significant heterogeneity (73.6%) between studies (P = 0.001). NAFLD prevalence was significantly higher in patients with PCOS compared to healthy control, with an overall OR of 3.93 (95% CI: 2.17, 7.11).There was no significant publication bias based on Begg's and Egger's tests. CONCLUSIONS According to the results of this meta-analysis, there was a high risk of NAFLD in women with PCOS. We suggest evaluating patients with PCOS regarding NAFLD.
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Affiliation(s)
- Mahdi Ramezani-Binabaj
- Students' Research Committee, Baqiyatallah University of Medical Sciences, Tehran, IR Iran
- Middle East Liver Diseases Center (MELD), Tehran, IR Iran
| | - Mohsen Motalebi
- Nephrology and Urology Research Center, Baqiyatallah University of Medical Sciences, Tehran, IR Iran
| | - Hamidreza Karimi-sari
- Students' Research Committee, Baqiyatallah University of Medical Sciences, Tehran, IR Iran
| | - Mohammad Saeid Rezaee-Zavareh
- Students' Research Committee, Baqiyatallah University of Medical Sciences, Tehran, IR Iran
- Middle East Liver Diseases Center (MELD), Tehran, IR Iran
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Kelley CE, Brown AJ, Diehl AM, Setji TL. Review of nonalcoholic fatty liver disease in women with polycystic ovary syndrome. World J Gastroenterol 2014; 20:14172-84. [PMID: 25339805 PMCID: PMC4202347 DOI: 10.3748/wjg.v20.i39.14172] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2014] [Revised: 04/11/2014] [Accepted: 04/30/2014] [Indexed: 02/07/2023] Open
Abstract
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-aged women. Women with PCOS frequently have metabolic complications including insulin resistance (IR), early diabetes, hypertension and dyslipidemia. Recent studies have demonstrated an association between PCOS and another metabolic complication: nonalcoholic fatty liver disease (NAFLD). NAFLD occurs as a result of abnormal lipid handling by the liver, which sensitizes the liver to injury and inflammation. It can progress to nonalcoholic steatohepatitis (NASH), which is characterized by hepatocyte injury and apoptosis. With time and further inflammation, NASH can progress to cirrhosis. Thus, given the young age at which NAFLD may occur in PCOS, these women may be at significant risk for progressive hepatic injury over the course of their lives. Many potential links between PCOS and NAFLD have been proposed, most notably IR and hyperandrogenemia. Further studies are needed to clarify the association between PCOS and NAFLD. In the interim, clinicians should be aware of this connection and consider screening for NAFLD in PCOS patients who have other metabolic risk factors. The optimal method of screening is unknown. However, measuring alanine aminotransferase and/or obtaining ultrasound on high-risk patients can be considered. First line treatment consists of lifestyle interventions and weight loss, with possible pharmacologic interventions in some cases.
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Lai H, Jia X, Yu Q, Zhang C, Qiao J, Guan Y, Kang J. High-fat diet induces significant metabolic disorders in a mouse model of polycystic ovary syndrome. Biol Reprod 2014; 91:127. [PMID: 25100714 DOI: 10.1095/biolreprod.114.120063] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Polycystic ovary syndrome (PCOS) is the most common female endocrinopathy associated with both reproductive and metabolic disorders. Dehydroepiandrosterone (DHEA) is currently used to induce a PCOS mouse model. High-fat diet (HFD) has been shown to cause obesity and infertility in female mice. The possible effect of an HFD on the phenotype of DHEA-induced PCOS mice is unknown. The aim of the present study was to investigate both reproductive and metabolic features of DHEA-induced PCOS mice fed a normal chow or a 60% HFD. Prepubertal C57BL/6 mice (age 25 days) on the normal chow or an HFD were injected (s.c.) daily with the vehicle sesame oil or DHEA for 20 consecutive days. At the end of the experiment, both reproductive and metabolic characteristics were assessed. Our data show that an HFD did not affect the reproductive phenotype of DHEA-treated mice. The treatment of HFD, however, caused significant metabolic alterations in DHEA-treated mice, including obesity, glucose intolerance, dyslipidemia, and pronounced liver steatosis. These findings suggest that HFD induces distinct metabolic features in DHEA-induced PCOS mice. The combined DHEA and HFD treatment may thus serve as a means of studying the mechanisms involved in metabolic derangements of this syndrome, particularly in the high prevalence of hepatic steatosis in women with PCOS.
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Affiliation(s)
- Hao Lai
- Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China
| | - Xiao Jia
- Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China
| | - Qiuxiao Yu
- Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China
| | - Chenglu Zhang
- Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China
| | - Jie Qiao
- Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, Beijing, China
| | - Youfei Guan
- Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China
| | - Jihong Kang
- Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China
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Caldwell ASL, Middleton LJ, Jimenez M, Desai R, McMahon AC, Allan CM, Handelsman DJ, Walters KA. Characterization of reproductive, metabolic, and endocrine features of polycystic ovary syndrome in female hyperandrogenic mouse models. Endocrinology 2014; 155:3146-59. [PMID: 24877633 DOI: 10.1210/en.2014-1196] [Citation(s) in RCA: 233] [Impact Index Per Article: 21.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Polycystic ovary syndrome (PCOS) affects 5-10% of women of reproductive age, causing a range of reproductive, metabolic and endocrine defects including anovulation, infertility, hyperandrogenism, obesity, hyperinsulinism, and an increased risk of type 2 diabetes and cardiovascular disease. Hyperandrogenism is the most consistent feature of PCOS, but its etiology remains unknown, and ethical and logistic constraints limit definitive experimentation in humans to determine mechanisms involved. In this study, we provide the first comprehensive characterization of reproductive, endocrine, and metabolic PCOS traits in 4 distinct murine models of hyperandrogenism, comprising prenatal dihydrotestosterone (DHT, potent nonaromatizable androgen) treatment during days 16-18 of gestation, or long-term treatment (90 days from 21 days of age) with DHT, dehydroepiandrosterone (DHEA), or letrozole (aromatase inhibitor). Prenatal DHT-treated mature mice exhibited irregular estrous cycles, oligo-ovulation, reduced preantral follicle health, hepatic steatosis, and adipocyte hypertrophy, but lacked overall changes in body-fat composition. Long-term DHT treatment induced polycystic ovaries displaying unhealthy antral follicles (degenerate oocyte and/or > 10% pyknotic granulosa cells), as well as anovulation and acyclicity in mature (16-week-old) females. Long-term DHT also increased body and fat pad weights and induced adipocyte hypertrophy and hypercholesterolemia. Long-term letrozole-treated mice exhibited absent or irregular cycles, oligo-ovulation, polycystic ovaries containing hemorrhagic cysts atypical of PCOS, and displayed no metabolic features of PCOS. Long-term dehydroepiandrosterone treatment produced no PCOS features in mature mice. Our findings reveal that long-term DHT treatment replicated a breadth of ovarian, endocrine, and metabolic features of human PCOS and provides the best mouse model for experimental studies of PCOS pathogenesis.
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Affiliation(s)
- A S L Caldwell
- Andrology Laboratory (A.S.L.C., L.J.M., M.J., R.D., C.M.A.,D.J.H., K.A.W.) and Biogerontology Laboratory (A.C.M.), ANZAC Research Institute, University of Sydney, Sydney, New South Wales 2139, Australia
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