The Subcutaneous Adipose Microenvironment as a Determinant of Body Fat Development in Polycystic Ovary Syndrome

Daniel A Dumesic, Melody A Rasouli, Jessica D Katz, Gwyneth G Lu, Devyani Dharanipragada, Adina F Turcu, Tristan R Grogan, Kimberly E Flores, Clara E Magyar, David H Abbott, Gregorio D Chazenbalk
Journal of the Endocrine Society, Volume 8, Issue 11, November 2024, bvae162
https://doi.org/10.1210/jendso/bvae162

Abstract

Context

Adipose steroid metabolism modifies body fat development in polycystic ovary syndrome (PCOS).

Objective

To determine whether subcutaneous (SC) abdominal adipose aldo-keto reductase 1C3 (AKR1C3; a marker of testosterone generation) is increased in normal-weight women with PCOS vs age- and body mass index (BMI)-matched normoandrogenic ovulatory women (controls) and is related to SC abdominal adipose activator protein-1 (AP-1; a marker of adipocyte differentiation) and/or androgen receptor (AR) protein expression in predicting fat accretion.

Design

Prospective cohort study.

Setting

Academic center.

Patients

Eighteen normal-weight PCOS women; 17 age- and BMI-matched controls.

Intervention(s)

Circulating hormone/metabolic determinations, intravenous glucose tolerance testing, total body dual-energy x-ray absorptiometry, SC abdominal fat biopsy, immunohistochemistry.

Main Outcome Measure(s)

Clinical characteristics, hormonal concentrations, body fat distribution, SC adipose AKR1C3, AR, and AP-1 protein expression.

Results

Women with PCOS had significantly higher serum androgen levels and greater android/gynoid fat mass ratios than controls. SC adipose AKR1C3, AR, and AP-1 protein expressions were comparable between the study groups, but groups differed in correlations. In PCOS women vs controls, SC adipose AKR1C3 protein expression correlated positively with android and gynoid fat masses and negatively with SC adipose AP-1 protein expression. SC adipose AR protein expression correlated negatively with fasting serum free fatty acid and high-density lipoprotein levels. In both study groups, SC adipose AKR1C3 protein expression negatively correlated with serum cortisol levels.

Conclusion

In normal-weight PCOS women, SC abdominal adipose AKR1C3 protein expression, in combination with intra-adipose AP-1 and AR-dependent events, predicts fat accretion in the presence of physiological cortisol levels.

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