Endocrine Abstracts (2015) 38 P240 | DOI: 10.1530/endoabs.38.P240

Effects of androgen on the adipokinome and metabolic genes in white and brown adipose tissue

Avi Lerner, Drashti Kewada, Anthony Okolo, Kate Hardy & Stephan Franks

Imperial College London, London, UK.

Polycystic ovary syndrome (PCOS) is a common endocrinopathy that is associated with an adverse metabolic profile including insulin resistance and dyslipidaemia. Hyperandrogenism is the hallmark of PCOS and obesity increases androgen synthesis, partly due to accompanying hyperinsulinemia but also as a result of adipokines affecting ovarian steroidogenesis (Comim et al., 2013, PLoS ONE 8(11). Adipokines are factors secreted by adipose tissue and while a clear link between obesity and the severity of PCOS exists, the relationship between hyperandrogenism and adipose tissue is less clear. In this study, a systems approach was used to investigate effects of androgen treatment on the adipokinome. Immortalised mouse white and brown preadipocytes were fully differentiated for 14 days and then treated with either dihydrotestosterone (DHT) or control for 24 h. Quantitative PCR was then used to analyse differential gene expression for a panel of 25 adipokines. Our results show that hyperandrogenism leads to dysregulation of the adipokinome in adipose tissue with potential impact on the secretory function of adipocytes. Interestingly, brown adipocytes (BAT) were far more responsive to androgen treatment than white adipocytes (WAT). Several of the affected genes are involved in BAT identity and thermogenesis as well as adipokine production. In the light of this we extended our investigation and treated explants of mouse inter-scapular BAT with either DHT or control for 24 h. The results show that DHT treatment reduces expression of key markers of BAT identity and genes implicated in thermogenesis, including UCP1 (P<0.05), PGC-1 (P<0.05) and Cidea (P<0.05). Furthermore, androgen treatment was shown to significantly attenuate (P<0.05) the β-adrenoceptor-stimulated increase in UCP1 expression in brown adipocytes. These results show that androgens not only affect WAT but also have significant effects on BAT with respect to genes that are involved in both adipokine synthesis and in energy expenditure.

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