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

1
Division of Longevity and Biofunctional Medicine, School of Korean Medicine, Pusan National University, 49 Busandaehak-ro, Mulgeum-eup, Yangsan-si, Gyeongnam 50612, Korea
2
Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 164 Frelinghuysen Road, Piscataway, NJ 08854, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Alessandro Mantovani and Andrea Dalbeni
Int. J. Mol. Sci. 2021, 22(20), 11085; https://doi.org/10.3390/ijms222011085
Received: 22 September 2021 / Revised: 9 October 2021 / Accepted: 10 October 2021 / Published: 14 October 2021
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. View Full-Text
Keywords: diacylglycerol acyltransferase 2; histone demethylase KDM7A; histone methylation; hepatic steatosis; nonalcoholic fatty liver disease; triglyceride diacylglycerol acyltransferase 2; histone demethylase KDM7A; histone methylation; hepatic steatosis; nonalcoholic fatty liver disease; triglyceride
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MDPI and ACS Style

Kim, J.-H.; Nagappan, A.; Jung, D.Y.; Suh, N.; Jung, M.H. Histone Demethylase KDM7A Contributes to the Development of Hepatic Steatosis by Targeting Diacylglycerol Acyltransferase 2. Int. J. Mol. Sci. 2021, 22, 11085. https://doi.org/10.3390/ijms222011085

AMA Style

Kim J-H, Nagappan A, Jung DY, Suh N, Jung MH. Histone Demethylase KDM7A Contributes to the Development of Hepatic Steatosis by Targeting Diacylglycerol Acyltransferase 2. International Journal of Molecular Sciences. 2021; 22(20):11085. https://doi.org/10.3390/ijms222011085

Chicago/Turabian Style

Kim, Ji-Hyun, Arukumar Nagappan, Dae Y. Jung, Nanjoo Suh, and Myeong H. Jung 2021. "Histone Demethylase KDM7A Contributes to the Development of Hepatic Steatosis by Targeting Diacylglycerol Acyltransferase 2" International Journal of Molecular Sciences 22, no. 20: 11085. https://doi.org/10.3390/ijms222011085

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