Vitamin C Inhibits the Metabolic Changes Induced by Tet1 Insufficiency Under High Fat Diet Stress.

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.