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 were fed a high fat diet (HFD). Higher weight gain and more severe hepatic steatosis, accompanied by reduced 5-hydromethylcytosine (5hmC) levels, were found in the white adipose tissue and liver of Tet1+/- mice. Accumulated lipids were observed in palmitic acid or oleic acid treated primary hepatocytes derived from Tet1+/- mice, which were rescued by Tet1 overexpression or vitamin C treatment. Bisulfite sequencing revealed higher DNA methylation levels on lipolysis related genes in the liver of Tet1+/- mice. Notably, oral intake of vitamin C normalized DNA methylation levels, promoted lipolysis and decreased obesity in HFD-fed Tet1+/- mice.
CONCLUSIONS
Our results revealed a novel function of Tet1 in obesity and provided a new mechanism for the beneficial role of vitamin C in metabolic diseases through enhanced Tet1 activity. This article is protected by copyright. All rights reserved.