Polycystic ovary syndrome (PCOS) is a common endocrinopathy that is associated with hyperandrogenism- and an adverse metabolic profile including obesity and insulin resistance. Women with PCOS and raised androgen levels exhibit reduced postprandial thermogenesis and this is thought to predispose women with PCOS to weight gain (Robinson et al., 1992, Clin Endocrinol 36: 537543). Brown adipose tissue (BAT) is important in the dissipation of energy in the form of heat and changes in BAT could explain the reduction of postprandial thermogenesis found in women with PCOS. In this study, we investigated the effect of androgen on the differentiation of BAT, as well as, expression of BAT and mitochondrial genes. Mouse brown preadipocytes were differentiated for 7 days in the presence or absence of the potent androgen dihydrotestosterone (DHT, 10 nM to 10 μM). Our results show that androgen inhibits brown adipose differentiation in a dose dependent manner. We then treated explants of mouse interscapular BAT with either 100 nM DHT or vehicle for 24 hours. Androgen treatment resulted in reduced expression of several key BAT genes, including UCP1 (P<0.05), PGC-1 (P<0.05) and Cidea (P<0.05). In contrast, genes involved in mitochondrial function were unaffected by androgen treatment. In light of this we have begun to investigate the expression of brown adipose tissue genes invisceral and subcutaneous adipose tissue from women with and without PCOS. Our results show that genes such as UCP1, PGC1 and β3-AR are differentially expressed between visceral and subcutaneous depots. Furthermore, preliminary expression profiles of women with PCOS are consistent with ex-vivostudies of mouse adipose treated with DHT. Together, these data show that androgen causes a whitening of adipose tissue and could provide a molecular explanation for reduced postprandial thermogenesis and the tendency for obesity in women with PCOS.
11 Jul 2016 - 11 Jul 2016