Involvement of endogenous testosterone in hepatic steatosis in women with polycystic ovarian syndrome

•In this study, we report that the levels of alanine transaminase (ALT) and aspartate transaminase (AST) were increased in women with polycystic ovarian syndrome (PCOS).•A strong correlation between testosterone and AST levels was also observed.•After treatment with letrozole, an aromatase inhibitor, rats were significantly more obese, with animals developing hepatic steatosis and moderate insulin resistance.•Additional experiments revealed that HepG2 cells treated with dihydrotestosterone inhibited the AMP-activated protein kinase alpha pathway, thereby causing steatosis.•In summary, our results show that an elevated testosterone level can induce hepatic steatosis. The prevalence of nonalcoholic fatty liver disease (NAFLD) is higher in women with polycystic ovarian syndrome (PCOS) than that in healthy women. This association can be explained in part by the resistance to insulin and the prevalence of obesity, which are fueled by high androgen levels. However, there is little evidence of the involvement of endogenous testosterone in hepatic steatosis in women with PCOS. Here, we treated Sprague Dawley rats with the aromatase inhibitor, letrozole, to increase the endogenous testosterone level and to decrease the estradiol levels. We also quantified the testosterone levels in human serum specimens and HepG2 cells to investigate the effects of androgens on hepatic steatosis and liver dysfunction. Twenty-nine PCOS patients and twenty healthy women were enrolled. Alanine transaminase and aspartate transaminase (AST) levels were increased in women with PCOS, and a strong correlation between testosterone and AST levels was observed. After letrozole treatment for 90 days, rats were significantly more obese, with animals developing hepatic steatosis and moderate insulin resistance. Additional experiments revealed that excess androgen inhibited the AMP-activated protein kinase alpha pathway in letrozole-treated livers and dihydrotestosterone (DHT)-treated HepG2 cells, thereby causing steatosis. Our results show that an elevated endogenous testosterone level can induce hepatic steatosis. Decreasing the endogenous testosterone level in hepatocytes may represent a new approach in the treatment of NAFLD in PCOS patients.