https://orcid.org/0000-0002-3917-0483
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Fernando Bril, Uche Ezeh, Mina Amiri, Sana Hatoum, Lauren Pace, Yen-Hao Chen, Fred Bertrand, Barbara Gower, Ricardo Azziz, Adipose Tissue Dysfunction in Polycystic Ovary Syndrome, The Journal of Clinical Endocrinology & Metabolism, Volume 109, Issue 1, January 2024, Pages 10–24, https://doi.org/10.1210/clinem/dgad356
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Abstract
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.
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.
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.
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.
