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.
Keywords: DNA methylation; Tet1; lipid metabolism; obesity; vitamin C.
© 2021 Wiley-VCH GmbH.