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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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 |
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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 |
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