Vitamin E Modifies High-Fat Diet-Induced Increase of DNA Strand Breaks, and Changes in Expression and DNA Methylation of Dnmt1 and MLH1 in C57BL/6J Male Mice

Abstract

Obesity is associated with low-grade inflammation, increased ROS production and DNA damage. Supplementation with antioxidants might ameliorate DNA damage and support epigenetic regulation of DNA repair. C57BL/6J male mice were fed a high-fat (HFD) or a control diet (CD) with and without vitamin E supplementation (4.5 mg/kg body weight (b.w.)) for four months. DNA damage, DNA promoter methylation and gene expression of <i>Dnmt1</i> and a DNA repair gene (<i>MLH1</i>) were assayed in liver and colon. The HFD resulted in organ specific changes in DNA damage, the epigenetically important <i>Dnmt1</i> gene, and the DNA repair gene <i>MLH1</i>. Vitamin E reduced DNA damage and showed organ-specific effects on <i>MLH1</i> and <i>Dnmt1</i> gene expression and methylation. These results suggest that interventions with antioxidants and epigenetic active food ingredients should be developed as an effective prevention for obesity-and oxidative stress-induced health risks.