Department of Veterinary Biochemistry, College of Veterinary Medicine, Chungnam National University, Daejeon 34134, Korea.
Department of Veterinary Toxicology, College of Veterinary Medicine, Chungnam National University, Daejeon 34134, Korea.
Int J Mol Sci. 2021 Jul 23;22(15):7904. doi: 10.3390/ijms22157904.
The incidence of non-alcoholic fatty liver disease (NAFLD) increases in males aged >45 years, which indicates that androgens are associated with the development and/or progression of NAFLD, although excess dietary intake is the primary causative factor. However, it is uncertain how androgens are involved in the metabolic process of NAFLD, which is associated with the state of steatosis in hepatocytes. To investigate whether androgen receptor (AR) signaling influences NAFLD development, the state of steatosis was monitored in mouse livers and hepatocytes with or without androgens. As a result, hepatic lipid droplets, expression of AR, and phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) increased in the presence of testosterone. Concurrently, the expression of LKB1, an upstream regulator of AMPK, was increased by testosterone treatment. We observed that the fluctuation of AMPK-ACC signaling, which plays an important role in lipogenesis, depends on the presence of testosterone and AR. Additionally, we demonstrated that testosterone bound AR was recruited to the promoter of the gene and induced LKB1 expression. Our study highlights a novel mechanism by which testosterone modulates NAFLD development by inducing the mRNA expression of .
非酒精性脂肪性肝病（NAFLD）的发病率在 >45 岁的男性中增加，这表明雄激素与 NAFLD 的发生和/或进展有关，尽管过量的饮食摄入是主要的致病因素。然而，雄激素如何参与 NAFLD 的代谢过程尚不清楚，这与肝细胞脂肪变性的状态有关。为了研究雄激素受体（AR）信号是否影响 NAFLD 的发生，在有或没有雄激素的情况下监测了小鼠肝脏和肝细胞中的脂肪变性状态。结果表明，在睾酮存在的情况下，肝内脂质滴、AR 的表达以及 AMP 激活的蛋白激酶（AMPK）和乙酰辅酶 A 羧化酶（ACC）的磷酸化增加。同时，LKB1 的表达，一种 AMPK 的上游调节剂，也被睾酮处理所增加。我们观察到，在脂肪生成中起重要作用的 AMPK-ACC 信号的波动取决于睾酮和 AR 的存在。此外，我们证明，与 AR 结合的睾酮被募集到 基因的启动子上，并诱导 LKB1 的表达。我们的研究强调了一种新的机制，即睾酮通过诱导 基因的 mRNA 表达来调节 NAFLD 的发生和发展。
