Adipose Steroid Signaling and Fat Accumulation in Normal-Weight Women with PCOS

Emerging research continues to reveal the complex interplay between steroid metabolism and adipose tissue function in women with polycystic ovary syndrome (PCOS). A recent prospective cohort study offers new insights into how subcutaneous (SC) abdominal adipose tissue may contribute to fat accumulation—even in women with normal body weight.

The study examined AKR1C3, an enzyme that catalyzes local testosterone production, in SC abdominal fat from 18 normal-weight women with PCOS compared to 17 age- and BMI-matched normoandrogenic controls. Investigators also assessed activator protein-1 (AP-1), a regulator of adipocyte differentiation, and androgen receptor (AR) protein expression to determine their combined roles in predicting fat distribution and metabolic outcomes.

Despite similar AKR1C3, AR, and AP-1 protein levels between the groups, key differences in their associations with fat distribution emerged. Women with PCOS exhibited elevated serum androgens and higher android-to-gynoid fat mass ratios. In these women, AKR1C3 expression in SC adipose tissue was positively correlated with both android and gynoid fat mass and negatively correlated with AP-1 expression—suggesting altered adipogenic signaling. Additionally, SC adipose AR expression was negatively associated with fasting-free fatty acid and HDL cholesterol levels, indicating a potential role in lipid metabolism.

These findings underscore a metabolic adaptation in normal-weight women with PCOS—one that promotes fat accretion through intra-adipose steroid signaling pathways, even in the presence of physiological cortisol levels. As the modern environment increasingly favors obesity, understanding these subtle but significant pathways may prove essential in developing targeted interventions for lean PCOS phenotypes.

Source:   J Endocr Soc. 2024;8(11):bvae162.