气候变化领域集成服务门户(CCPortal): DNMT1 maintains metabolic fitness of adipocytes through acting as an epigenetic safeguard of mitochondrial dynamics

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DOI	10.1073/pnas.2021073118
	DNMT1 maintains metabolic fitness of adipocytes through acting as an epigenetic safeguard of mitochondrial dynamics
	Park Y.J.; Lee S.; Lim S.; Nahmgoong H.; Ji Y.; Huh J.Y.; Alfadda A.A.; Kim S.; Kim J.B.
发表日期	2021
ISSN	00278424
卷号	118 期号:11
英文摘要	White adipose tissue (WAT) is a key regulator of systemic energy metabolism, and impaired WAT plasticity characterized by enlargement of preexisting adipocytes associates with WAT dysfunction, obesity, and metabolic complications. However, the mechanisms that retain proper adipose tissue plasticity required for metabolic fitness are unclear. Here, we comprehensively showed that adipocyte-specific DNA methylation, manifested in enhancers and CTCF sites, directs distal enhancer-mediated transcriptomic features required to conserve metabolic functions of white adipocytes. Particularly, genetic ablation of adipocyte Dnmt1, the major methylation writer, led to increased adiposity characterized by increased adipocyte hypertrophy along with reduced expansion of adipocyte precursors (APs). These effects of Dnmt1 deficiency provoked systemic hyperlipidemia and impaired energy metabolism both in lean and obese mice. Mechanistically, Dnmt1 deficiency abrogated mitochondrial bioenergetics by inhibiting mitochondrial fission and promoted aberrant lipid metabolism in adipocytes, rendering adipocyte hypertrophy and WAT dysfunction. Dnmt1-dependent DNA methylation prevented aberrant CTCF binding and, in turn, sustained the proper chromosome architecture to permit interactions between enhancer and dynamin-1-like protein gene Dnm1l (Drp1) in adipocytes. Also, adipose DNMT1 expression inversely correlated with adiposity and markers of metabolic health but positively correlated with APspecific markers in obese human subjects. Thus, these findings support strategies utilizing Dnmt1 action on mitochondrial bioenergetics in adipocytes to combat obesity and related metabolic pathology. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Adiposity; Chromosome structure; DNA methylation; Metabolic disease; Mitochondria
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180233
作者单位	National Creative Research Initiatives Center for Adipocyte Structure and Function, Seoul National University, Seoul, 08826, South Korea; Institute of Molecular Biology and Genetics, Seoul National University, Seoul, 08826, South Korea; School of Biological Sciences, Seoul National University, Seoul, 08826, South Korea; Bioinformatics Institute, Seoul National University, Seoul, 08826, South Korea; Obesity Research Center, College of Medicine, King Saud University, Riyadh, 11461, Saudi Arabia; Department of Computer Science and Engineering, Institute of Engineering Research, Seoul National University, Seoul, 08826, South Korea; Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, 08826, South Korea
推荐引用方式 GB/T 7714	Park Y.J.,Lee S.,Lim S.,et al. DNMT1 maintains metabolic fitness of adipocytes through acting as an epigenetic safeguard of mitochondrial dynamics[J],2021,118(11).
APA	Park Y.J..,Lee S..,Lim S..,Nahmgoong H..,Ji Y..,...&Kim J.B..(2021).DNMT1 maintains metabolic fitness of adipocytes through acting as an epigenetic safeguard of mitochondrial dynamics.Proceedings of the National Academy of Sciences of the United States of America,118(11).
MLA	Park Y.J.,et al."DNMT1 maintains metabolic fitness of adipocytes through acting as an epigenetic safeguard of mitochondrial dynamics".Proceedings of the National Academy of Sciences of the United States of America 118.11(2021).