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Park, Jiyoung
Molecular Metabolism Lab.
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TonEBP/NFAT5 promotes obesity and insulin resistance by epigenetic suppression of white adipose tissue beiging

Author(s)
Lee, Hwan HeeAn, Seung MinYe, Byeong JinLee, Jun HoYoo, Eun JinJeong, Gyu WonKang, Hyun JeAlfadda, Assim A.Lim, Sun WooPark, JiyoungLee-Kwon, WhaseonKim, Jae BumChoi, Soo YounKwon, Hyug Moo
Issued Date
2019-08
DOI
10.1038/s41467-019-11302-w
URI
https://scholarworks.unist.ac.kr/handle/201301/27385
Fulltext
https://www.nature.com/articles/s41467-019-11302-w
Citation
NATURE COMMUNICATIONS, v.10, pp.3536
Abstract
Tonicity-responsive enhancer binding protein (TonEBP or NFAT5) is a regulator of cellular adaptation to hypertonicity, macrophage activation and T-cell development. Here we report that TonEBP is an epigenetic regulator of thermogenesis and obesity. In mouse subcutaneous adipocytes, TonEBP expression increases > 50-fold in response to high-fat diet (HFD) feeding. Mice with TonEBP haplo-deficiency or adipocyte-specific TonEBP deficiency are resistant to HFD-induced obesity and metabolic defects (hyperglycemia, hyperlipidemia, and hyperinsulinemia). They also display increased oxygen consumption, resistance to hypothermia, and beiging of subcutaneous fat tissues. TonEBP suppresses the promoter of beta 3-adrenoreceptor gene, a critical regulator of lipolysis and thermogenesis, in ex vivo and cultured adipocytes. This involves recruitment of DNMT1 DNA methylase and methylation of the promoter. In human subcutaneous adipocytes TonEBP expression displays a correlation with body mass index but an inverse correlation with beta 3-adrenoreceptor expression. Thus, TonEBP is an attractive therapeutic target for obesity, insulin resistance, and hyperlipidemia.
Publisher
NATURE PUBLISHING GROUP
ISSN
2041-1723
Keyword
INFLAMMATIONTRANSCRIPTIONEXPRESSIONHISTONEBETA(3)-ADRENERGIC RECEPTOR AGONISTENHANCER-BINDING PROTEINENERGY-EXPENDITUREDNA METHYLATIONHUMAN BROWNFAT-CELL

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