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- Title
Hepatic LKB1 Reduces the Progression of Non-Alcoholic Fatty Liver Disease via Genomic Androgen Receptor Signaling.
- Authors
Heo, Jun H.; Lee, Sang R.; Jo, Seong Lae; Ko, Je-Won; Kwon, Hyo-Jung; Hong, Eui-Ju
- Abstract
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.
- Subjects
NON-alcoholic fatty liver disease; ANDROGEN receptors; FOOD consumption; TESTOSTERONE; ACETYL-CoA carboxylase; PROTEIN kinases
- Publication
International Journal of Molecular Sciences, 2021, Vol 22, Issue 15, p7904
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms22157904