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Adipose Tissue Dysfunction in Polycystic Ovary Syndrome
Open accessAbstract
Purpose: Polycystic ovary syndrome (PCOS) is a complex genetic trait and the most common endocrine disorder of women, clinically evident in 5% to 15% of reproductive-aged women globally, with associated cardiometabolic dysfunction. Adipose tissue (AT) dysfunction appears to play an important role in the pathophysiology of PCOS even in patients who do not have excess adiposity. Methods: We undertook a systematic review concerning AT dysfunction in PCOS, and prioritized studies that assessed AT function directly. We also explored therapies that targeted AT dysfunction for the treatment of PCOS. Results: Various mechanisms of AT dysfunction in PCOS were identified including dysregulation in storage capacity, hypoxia, and hyperplasia; impaired adipogenesis; impaired insulin signaling and glucose transport; dysregulated lipolysis and nonesterified free fatty acids (NEFAs) kinetics; adipokine and cytokine dysregulation and subacute inflammation; epigenetic dysregulation; and mitochondrial dysfunction and endoplasmic reticulum and oxidative stress. Decreased glucose transporter-4 expression and content in adipocytes, leading to decreased insulin-mediated glucose transport in AT, was a consistent abnormality despite no alterations in insulin binding or in IRS/PI3K/Akt signaling. Adiponectin secretion in response to cytokines/chemokines is affected in PCOS compared to controls. Interestingly, epigenetic modulation via DNA methylation and microRNA regulation appears to be important mechanisms underlying AT dysfunction in PCOS. Conclusion: AT dysfunction, more than AT distribution and excess adiposity, contributes to the metabolic and inflammation abnormalities of PCOS. Nonetheless, many studies provided contradictory, unclear, or limited data, highlighting the urgent need for additional research in this important field.
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“Visceral adipose tissue dysfunction plays a central role in the development of IR, chronic low-grade inflammation, and cardiometabolic complications in PCOS patients.”
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Metadata
- Authors
- Bril, F., Ezeh, U., Amiri, M., Hatoum, S., Pace, L., Chen, Y.-H., Bertrand, F., Gower, B., & Azziz, R.
- Affiliations
- University of Alabama at Birmingham (US)
- Research Institute for Endocrine Sciences (IR)
- Foundation for Research and Education Excellence , Vestavia, AL 35243 , USA
- Department of Research, Biomere-West , Richmond, CA 94806 , USA
- Corresponding author
- Azziz, Ricardo
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2023-06-17
- Volume
- 109
- Issue
- 1
- Pages
- 10-24
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC10735305
- OpenAlex
- W4381047110
- Cited by
- 123
- References
- 156
- Citations by year
- 2026: 54 · 2025: 43 · 2024: 22 · 2023: 3
- FWCI
- 4.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1-K24-HD01346, R01-DK073632, R01-HD29364))
- Helping Hand of Los Angeles, Inc
- Research and Education Excellence
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Keywords
- polycystic ovary syndrome, adipose tissue dysfunction, insulin resistance, glucose transport, glucose transporter 4, adiponectin, adipokines, inflammation, epigenetic regulation, DNA methylation, microRNA, mitochondrial dysfunction, oxidative stress, endoplasmic reticulum stress, lipolysis, free fatty acids, adipocyte hyperplasia, adipogenesis, cardiometabolic dysfunction
- MeSH terms
- Adipose Tissue, Adult, Female, Glucose, Humans, Inflammation, Insulin, Insulin Resistance, Obesity, Polycystic Ovary Syndrome, Cytokines, Phosphatidylinositol 3-Kinases
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