High‐fat diet feeding enhances DNMTs’ mRNA and protein expression via increasing chromatin accessibility and decreasing ubiquitination‐mediated protein degradation, resulting in hypermethylation at the Klb promoter and subsequent downregulation of Klb expression; this in turn impairs fatty acid oxidation and oxidative phosphorylation and promotes the development of hepatic steatosis in mice. This evidence concerns the gene KLB and Hepatic steatosis.