Polycystic ovary syndrome (PCOS) is a common endocrinopathy is associated with an adverse metabolic profile including obesity, insulin resistance, and dyslipidaemia. Hyperandrogenism is the hallmark of PCOS and androgen production is increased in the presence of increased adiposity. While a clear link between obesity and the severity of PCOS exists, the relationship between hyperandrogenism and adipose tissue is less clear. Interestingly, women with PCOS and raised androgen levels exhibit reduced postprandial thermogenesis (Robinson et al. J Clin Endocrinol 1992 36 537). Brown adipose tissue (BAT) is important in non-shivering and postprandial thermogenesis. In this study, we investigated the effect of androgen treatment on the differentiation and gene expression of BAT. Immortalised mouse brown preadipocytes were differentiated for 14 days in the presence and absence of dihydrotestosterone (DHT). In addition, fully differentiated adipocytes were treated with DHT or control for 24 h. Adipogenesis was observed using Oil Red O staining and quantitative PCR was used to analyse differential gene expression for a panel of genes. Our results show that DHT treatment inhibits brown fat adipogenesis in a dose-dependent manner. Hyperandrogenism also causes dysregulation of normal gene expression and several markers for BAT and thermogenesis were significantly perturbed. These included downregulation of the adipokine desnutrin/ATGL (a key gene required for BAT identity and thermogenesis) (P<0.01) and C/EBPα (an important early regulator of brown adipose markers and normal energy metabolism) (P<0.01). Furthermore, DHT treatment caused distinctive adipokine profiles similar to those found in metabolic syndrome and insulin resistance such as reduced adiponectin (P<0.05) and raised PAI-1 (P<0.05). These results suggest that androgens play a role in brown adipocyte differentiation and function and lend support for a reciprocal relationship between androgens, BAT and thermogenesis.
Disclosure: MRC Program grant (P22061).
16 - 20 May 2015
European Society of Endocrinology