Subcutaneous Adipose Microenvironment Determines Body Fat Development in PCOS

Adipose steroid metabolism plays a crucial role in body fat development in women with polycystic ovary syndrome (PCOS). A new study investigated whether subcutaneous (SC) abdominal adipose aldo-keto reductase 1C3 (AKR1C3) – a marker of testosterone production, is elevated in normal-weight women with PCOS compared to age- and BMI-matched normoandrogenic women (controls), and if it relates to SC adipose activator protein-1 (AP-1)––that influences adipocyte differentiation––and androgen receptor (AR) protein expression in predicting fat accumulation.

This was a prospective cohort study wherein 18 normal-weight women with PCOS were compared to 17 controls. Various assessments, including hormone and metabolic tests, glucose tolerance testing, body composition analysis, and SC abdominal fat biopsies, were performed. The study measured clinical characteristics, hormone levels, body fat distribution, and expressions of SC adipose AKR1C3, AR, and AP-1 proteins.

The results revealed that PCOS women had higher serum androgen levels and greater android-to-gynoid fat mass ratios compared to controls. Although SC adipose AKR1C3, AR, and AP-1 protein levels were similar between the groups, their correlations differed. In PCOS women, SC adipose AKR1C3 expression was positively correlated with android and gynoid fat mass and negatively correlated with SC adipose AP-1 expression. SC adipose AR expression was negatively associated with fasting, free fatty acid and HDL levels. In both groups, SC adipose AKR1C3 expression negatively correlated with cortisol levels.

Thus, SC abdominal adipose AKR1C3 expression, along with AP-1 and AR-related events, predicts fat accumulation in normal-weight PCOS women, even with normal cortisol levels. These findings suggest a metabolic adaptation in PCOS women, predisposing them to weight gain and fat-related complications in modern obesogenic environments.

Source: Dumesic DA, Rasouli MA, Katz JD, et al. J Endocr Soc. 2024;8(11):bvae162. Published 2024 Sep 17. doi:10.1210/jendso/bvae162