Cargando…

Histone Demethylase KDM7A Contributes to the Development of Hepatic Steatosis by Targeting Diacylglycerol Acyltransferase 2

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. While the development of NAFLD is correlated with aberrant histone methylation, modifiers of histone methylation involved in this event remain poorly understood. Here, we studied the functional role of the histone dem...

Descripción completa

Detalles Bibliográficos
Autores principales: Kim, Ji-Hyun, Nagappan, Arukumar, Jung, Dae Young, Suh, Nanjoo, Jung, Myeong Ho
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8539991/
https://www.ncbi.nlm.nih.gov/pubmed/34681759
http://dx.doi.org/10.3390/ijms222011085
_version_ 1784588879600287744
author Kim, Ji-Hyun
Nagappan, Arukumar
Jung, Dae Young
Suh, Nanjoo
Jung, Myeong Ho
author_facet Kim, Ji-Hyun
Nagappan, Arukumar
Jung, Dae Young
Suh, Nanjoo
Jung, Myeong Ho
author_sort Kim, Ji-Hyun
collection PubMed
description Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. While the development of NAFLD is correlated with aberrant histone methylation, modifiers of histone methylation involved in this event remain poorly understood. Here, we studied the functional role of the histone demethylase KDM7A in the development of hepatic steatosis. KDM7A overexpression in AML12 cells upregulated diacylglycerol acyltransferase 2 (DGAT2) expression and resulted in increased intracellular triglyceride (TG) accumulation. Conversely, KDM7A knockdown reduced DGAT2 expression and TG accumulation, and significantly reversed free fatty acids-induced TG accumulation. Additionally, adenovirus-mediated overexpression of KDM7A in mice resulted in hepatic steatosis, which was accompanied by increased expression of hepatic DGAT2. Furthermore, KDM7A overexpression decreased the enrichment of di-methylation of histone H3 lysine 9 (H3K9me2) and H3 lysine 27 (H3K27me2) on the promoter of DGAT2. Taken together, these results indicate that KDM7A overexpression induces hepatic steatosis through upregulation of DGAT2 by erasing H3K9me2 and H3K27me2 on the promoter.
format Online
Article
Text
id pubmed-8539991
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-85399912021-10-24 Histone Demethylase KDM7A Contributes to the Development of Hepatic Steatosis by Targeting Diacylglycerol Acyltransferase 2 Kim, Ji-Hyun Nagappan, Arukumar Jung, Dae Young Suh, Nanjoo Jung, Myeong Ho Int J Mol Sci Article Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. While the development of NAFLD is correlated with aberrant histone methylation, modifiers of histone methylation involved in this event remain poorly understood. Here, we studied the functional role of the histone demethylase KDM7A in the development of hepatic steatosis. KDM7A overexpression in AML12 cells upregulated diacylglycerol acyltransferase 2 (DGAT2) expression and resulted in increased intracellular triglyceride (TG) accumulation. Conversely, KDM7A knockdown reduced DGAT2 expression and TG accumulation, and significantly reversed free fatty acids-induced TG accumulation. Additionally, adenovirus-mediated overexpression of KDM7A in mice resulted in hepatic steatosis, which was accompanied by increased expression of hepatic DGAT2. Furthermore, KDM7A overexpression decreased the enrichment of di-methylation of histone H3 lysine 9 (H3K9me2) and H3 lysine 27 (H3K27me2) on the promoter of DGAT2. Taken together, these results indicate that KDM7A overexpression induces hepatic steatosis through upregulation of DGAT2 by erasing H3K9me2 and H3K27me2 on the promoter. MDPI 2021-10-14 /pmc/articles/PMC8539991/ /pubmed/34681759 http://dx.doi.org/10.3390/ijms222011085 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
Kim, Ji-Hyun
Nagappan, Arukumar
Jung, Dae Young
Suh, Nanjoo
Jung, Myeong Ho
Histone Demethylase KDM7A Contributes to the Development of Hepatic Steatosis by Targeting Diacylglycerol Acyltransferase 2
title Histone Demethylase KDM7A Contributes to the Development of Hepatic Steatosis by Targeting Diacylglycerol Acyltransferase 2
title_full Histone Demethylase KDM7A Contributes to the Development of Hepatic Steatosis by Targeting Diacylglycerol Acyltransferase 2
title_fullStr Histone Demethylase KDM7A Contributes to the Development of Hepatic Steatosis by Targeting Diacylglycerol Acyltransferase 2
title_full_unstemmed Histone Demethylase KDM7A Contributes to the Development of Hepatic Steatosis by Targeting Diacylglycerol Acyltransferase 2
title_short Histone Demethylase KDM7A Contributes to the Development of Hepatic Steatosis by Targeting Diacylglycerol Acyltransferase 2
title_sort histone demethylase kdm7a contributes to the development of hepatic steatosis by targeting diacylglycerol acyltransferase 2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8539991/
https://www.ncbi.nlm.nih.gov/pubmed/34681759
http://dx.doi.org/10.3390/ijms222011085
work_keys_str_mv AT kimjihyun histonedemethylasekdm7acontributestothedevelopmentofhepaticsteatosisbytargetingdiacylglycerolacyltransferase2
AT nagappanarukumar histonedemethylasekdm7acontributestothedevelopmentofhepaticsteatosisbytargetingdiacylglycerolacyltransferase2
AT jungdaeyoung histonedemethylasekdm7acontributestothedevelopmentofhepaticsteatosisbytargetingdiacylglycerolacyltransferase2
AT suhnanjoo histonedemethylasekdm7acontributestothedevelopmentofhepaticsteatosisbytargetingdiacylglycerolacyltransferase2
AT jungmyeongho histonedemethylasekdm7acontributestothedevelopmentofhepaticsteatosisbytargetingdiacylglycerolacyltransferase2