Hepatic LKB1 Reduces the Progression of Non-Alcoholic Fatty Liver Disease via Genomic Androgen Receptor Signaling

被引:7
|
作者
Heo, Jun H. [1 ]
Lee, Sang R. [1 ]
Jo, Seong Lae [1 ]
Ko, Je-Won [2 ]
Kwon, Hyo-Jung [3 ]
Hong, Eui-Ju [1 ]
机构
[1] Chungnam Natl Univ, Coll Vet Med, Dept Vet Biochem, Daejeon 34134, South Korea
[2] Chungnam Natl Univ, Coll Vet Med, Dept Vet Toxicol, Daejeon 34134, South Korea
[3] Chungnam Natl Univ, Coll Vet Med, Dept Vet Pathol, Daejeon 34134, South Korea
基金
新加坡国家研究基金会;
关键词
testosterone; LKB1; NAFLD; AMPK; PROSTATE-CANCER CELLS; METABOLISM; GLUCOSE;
D O I
10.3390/ijms22157904
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 LKB1 gene and induced LKB1 expression. Our study highlights a novel mechanism by which testosterone modulates NAFLD development by inducing the mRNA expression of LKB1.
引用
收藏
页数:14
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