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Vitamin C Inhibits the Metabolic Changes Induced by Tet1 Insufficiency Under High Fat Diet Stress
Author(s) -
Yuan Yangmian,
Liu Chengyu,
Chen Xingrui,
Sun Yuyan,
Xiong Mingrui,
Fan Yu,
Petersen Robert B.,
Chen Hong,
Huang Kun,
Zheng Ling
Publication year - 2021
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.202100417
Subject(s) - dna demethylation , endocrinology , medicine , white adipose tissue , lipolysis , vitamin , adipose tissue , fatty liver , dna methylation , methylation , chemistry , biology , biochemistry , dna , gene , gene expression , disease
Scope DNA methylation contributes to obesity, but the role of the DNA demethylase ten‐eleven translocation protein 1 (Tet1) in obesity remains unclear. Vitamin C is a cofactor for the Tet family of proteins, but whether vitamin C can be used to treat obesity via Tet1 awaits clarification. Methods and Results Tet1 +/+ and Tet1 +/− mice are fed a high fat diet (HFD). Higher weight gain and more severe hepatic steatosis, accompanied by reduced 5‐hydromethylcytosine (5hmC) levels, are found in the white adipose tissue and liver of Tet1 +/− mice. Accumulated lipids are observed in palmitic acid or oleic acid treated primary hepatocytes derived from Tet1 +/− mice, which are rescued by Tet1 overexpression or vitamin C treatment. Bisulfite sequencing reveals higher DNA methylation levels on lipolysis related genes in the liver of Tet1 +/− mice. Notably, oral intake of vitamin C normalizes DNA methylation levels, promotes lipolysis, and decreases obesity in HFD‐fed Tet1 +/− mice. Conclusions The results reveal a novel function of Tet1 in obesity and provide a new mechanism for the beneficial role of vitamin C in metabolic diseases through enhanced Tet1 activity.