Long-term androgen-induced nonalcoholic fatty liver disease in a polycystic ovary syndrome mouse model is related to mitochondrial dysfunction

Abstract

Objective: Metabolic disorders are markedly common in women with polycystic ovary syndrome (PCOS), and nonalcoholic fatty liver disease (NAFLD) is observed in 30%–55% of all PCOS patients. Many studies have reported that autophagy and apoptosis, which are closely related to mitochondrial function, play important roles in the development of NAFLD. Therefore, in this study, we aimed to explore the role of mitochondrial dysfunction caused by liver apoptosis and autophagy imbalance in the development of NAFLD in a PCOS mouse model. Methods: We used a dihydrotestosterone (DHT)-induced PCOS model to mimic the pathological process of hyperandrogenism. Hematoxylin and eosin and Oil Red O staining assays were used to observe the pathological changes in the liver. Western blotting and quantitative real-time polymerase chain reaction were used to perform mitochondrion-related assays. Results: Hepatic steatosis and different degrees of inflammation were observed in the DHT-treated mice. The expression of molecules involved in the respiratory chain and aerobic respiration process was altered. The levels of the key molecules associated with apoptosis and autophagy were abnormal. Conclusions: Androgens may play a role in the process of hepatic steatosis development by affecting mitochondrial function and subsequently inducing apoptosis and autophagy. Such phenomena might be involved in the pathogenesis of NAFLD in women with PCOS.

Keywords

• apoptosis; autophagy; mitochondrial function; nonalcoholic fatty liver disease; polycystic ovary syndrome