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Histone H3K9 demethylase JMJD2B induces hepatic steatosis through upregulation of PPARγ2

Understanding the epigenetic mechanisms underlying the progression of hepatic steatosis is important for identifying new therapeutic targets against nonalcoholic fatty liver disease (NAFLD). We investigated the functional role of histone demethylase JMJD2B in the pathologic regulation of hepatic ste...

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Autores principales: Kim, Ji-Hyun, Jung, Dae Young, Nagappan, Arulkumar, Jung, Myeong Ho
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6137221/
https://www.ncbi.nlm.nih.gov/pubmed/30214048
http://dx.doi.org/10.1038/s41598-018-31953-x
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author Kim, Ji-Hyun
Jung, Dae Young
Nagappan, Arulkumar
Jung, Myeong Ho
author_facet Kim, Ji-Hyun
Jung, Dae Young
Nagappan, Arulkumar
Jung, Myeong Ho
author_sort Kim, Ji-Hyun
collection PubMed
description Understanding the epigenetic mechanisms underlying the progression of hepatic steatosis is important for identifying new therapeutic targets against nonalcoholic fatty liver disease (NAFLD). We investigated the functional role of histone demethylase JMJD2B in the pathologic regulation of hepatic steatosis. JMJD2B expression was markedly increased in HepG2 cells treated with palmitate and oleate or liver X receptor agonist T09013178 and in the liver of high-fat diet (HFD)-induced obese mice. Overexpression of JMJD2B using adenovirus in HepG2 cells stimulated the expression of peroxisome proliferator-activated receptor γ2 (PPARγ2) and its steatosis target genes associated with fatty acid uptake and lipid droplet formation, resulting in increased intracellular triglyceride (TG) accumulation. Conversely, knocking down JMJD2B using siRNA reversed JMJD2B-mediated effects in HepG2 cells. The JMJD2B-dependent upregulation of PPARγ2 was associated with the removal of di- and trimethylation of histone H3 lysine 9 on the promoter of PPARγ2. Furthermore, exogeneous expression of JMJD2B using adenovirus in mice resulted in hepatic steatosis when fed a HFD, which was accompanied with increased expression of hepatic PPARγ2 and its steatosis target genes. Together, our results provide novel insights into the pivotal role of JMJD2B in the development of hepatic steatosis through upregulation of PPARγ2 and steatosis target genes.
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spelling pubmed-61372212018-09-15 Histone H3K9 demethylase JMJD2B induces hepatic steatosis through upregulation of PPARγ2 Kim, Ji-Hyun Jung, Dae Young Nagappan, Arulkumar Jung, Myeong Ho Sci Rep Article Understanding the epigenetic mechanisms underlying the progression of hepatic steatosis is important for identifying new therapeutic targets against nonalcoholic fatty liver disease (NAFLD). We investigated the functional role of histone demethylase JMJD2B in the pathologic regulation of hepatic steatosis. JMJD2B expression was markedly increased in HepG2 cells treated with palmitate and oleate or liver X receptor agonist T09013178 and in the liver of high-fat diet (HFD)-induced obese mice. Overexpression of JMJD2B using adenovirus in HepG2 cells stimulated the expression of peroxisome proliferator-activated receptor γ2 (PPARγ2) and its steatosis target genes associated with fatty acid uptake and lipid droplet formation, resulting in increased intracellular triglyceride (TG) accumulation. Conversely, knocking down JMJD2B using siRNA reversed JMJD2B-mediated effects in HepG2 cells. The JMJD2B-dependent upregulation of PPARγ2 was associated with the removal of di- and trimethylation of histone H3 lysine 9 on the promoter of PPARγ2. Furthermore, exogeneous expression of JMJD2B using adenovirus in mice resulted in hepatic steatosis when fed a HFD, which was accompanied with increased expression of hepatic PPARγ2 and its steatosis target genes. Together, our results provide novel insights into the pivotal role of JMJD2B in the development of hepatic steatosis through upregulation of PPARγ2 and steatosis target genes. Nature Publishing Group UK 2018-09-13 /pmc/articles/PMC6137221/ /pubmed/30214048 http://dx.doi.org/10.1038/s41598-018-31953-x Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Kim, Ji-Hyun
Jung, Dae Young
Nagappan, Arulkumar
Jung, Myeong Ho
Histone H3K9 demethylase JMJD2B induces hepatic steatosis through upregulation of PPARγ2
title Histone H3K9 demethylase JMJD2B induces hepatic steatosis through upregulation of PPARγ2
title_full Histone H3K9 demethylase JMJD2B induces hepatic steatosis through upregulation of PPARγ2
title_fullStr Histone H3K9 demethylase JMJD2B induces hepatic steatosis through upregulation of PPARγ2
title_full_unstemmed Histone H3K9 demethylase JMJD2B induces hepatic steatosis through upregulation of PPARγ2
title_short Histone H3K9 demethylase JMJD2B induces hepatic steatosis through upregulation of PPARγ2
title_sort histone h3k9 demethylase jmjd2b induces hepatic steatosis through upregulation of pparγ2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6137221/
https://www.ncbi.nlm.nih.gov/pubmed/30214048
http://dx.doi.org/10.1038/s41598-018-31953-x
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