Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Heo, Jun H., Lee, Sang R., Jo, Seong Lae, Ko, Je-Won, Kwon, Hyo-Jung, Hong, Eui-Ju
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348493/
https://www.ncbi.nlm.nih.gov/pubmed/34360667
http://dx.doi.org/10.3390/ijms22157904
_version_ 1783735353773916160
author Heo, Jun H.
Lee, Sang R.
Jo, Seong Lae
Ko, Je-Won
Kwon, Hyo-Jung
Hong, Eui-Ju
author_facet Heo, Jun H.
Lee, Sang R.
Jo, Seong Lae
Ko, Je-Won
Kwon, Hyo-Jung
Hong, Eui-Ju
author_sort Heo, Jun H.
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8348493
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-83484932021-08-08 Hepatic LKB1 Reduces the Progression of Non-Alcoholic Fatty Liver Disease via Genomic Androgen Receptor Signaling Heo, Jun H. Lee, Sang R. Jo, Seong Lae Ko, Je-Won Kwon, Hyo-Jung Hong, Eui-Ju Int J Mol Sci Article 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. MDPI 2021-07-23 /pmc/articles/PMC8348493/ /pubmed/34360667 http://dx.doi.org/10.3390/ijms22157904 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Heo, Jun H.
Lee, Sang R.
Jo, Seong Lae
Ko, Je-Won
Kwon, Hyo-Jung
Hong, Eui-Ju
Hepatic LKB1 Reduces the Progression of Non-Alcoholic Fatty Liver Disease via Genomic Androgen Receptor Signaling
title Hepatic LKB1 Reduces the Progression of Non-Alcoholic Fatty Liver Disease via Genomic Androgen Receptor Signaling
title_full Hepatic LKB1 Reduces the Progression of Non-Alcoholic Fatty Liver Disease via Genomic Androgen Receptor Signaling
title_fullStr Hepatic LKB1 Reduces the Progression of Non-Alcoholic Fatty Liver Disease via Genomic Androgen Receptor Signaling
title_full_unstemmed Hepatic LKB1 Reduces the Progression of Non-Alcoholic Fatty Liver Disease via Genomic Androgen Receptor Signaling
title_short Hepatic LKB1 Reduces the Progression of Non-Alcoholic Fatty Liver Disease via Genomic Androgen Receptor Signaling
title_sort hepatic lkb1 reduces the progression of non-alcoholic fatty liver disease via genomic androgen receptor signaling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348493/
https://www.ncbi.nlm.nih.gov/pubmed/34360667
http://dx.doi.org/10.3390/ijms22157904
work_keys_str_mv AT heojunh hepaticlkb1reducestheprogressionofnonalcoholicfattyliverdiseaseviagenomicandrogenreceptorsignaling
AT leesangr hepaticlkb1reducestheprogressionofnonalcoholicfattyliverdiseaseviagenomicandrogenreceptorsignaling
AT joseonglae hepaticlkb1reducestheprogressionofnonalcoholicfattyliverdiseaseviagenomicandrogenreceptorsignaling
AT kojewon hepaticlkb1reducestheprogressionofnonalcoholicfattyliverdiseaseviagenomicandrogenreceptorsignaling
AT kwonhyojung hepaticlkb1reducestheprogressionofnonalcoholicfattyliverdiseaseviagenomicandrogenreceptorsignaling
AT hongeuiju hepaticlkb1reducestheprogressionofnonalcoholicfattyliverdiseaseviagenomicandrogenreceptorsignaling