Beschreibung:
In this study, we investigated epigenetic modifications in the promoter region of the leptin gene and related effects of dietary n‐3 polyunsaturated fatty acids (n‐3 FA) in diet induced obese (DIO) mice. Male C57 BL/6J mice were fed with two high‐fat diets with different fat types – sunflower oil (n‐3 FA deficient) and fish oil, with a low‐fat diet ‐‐ sunflower oil as control. Compared to the mice fed with the control diet, expressions of leptin in plasma and epididymal fat were increased 8 fold in the n‐3 PUFA deficient DIO mice (P<0.01), and fish oil n‐3 FA in the DIO diet reversed the increased leptin expressions. The mean methylation fractions in most CpG sites of the leptin promoter were higher in the DIO mice (77% and 75%) than those in control (70%) with increasing binding of methylated CpG binding protein 2 by 40%. Also, increased H3 acetylation and decreased H4 acetylation at the leptin promoter were found in n‐3 deficient DIO mice, and the increased H3 acetylation was inhibited by dietary n‐3 FA. Methylation of Lys4 on H3 (H3K4) was reduced and that of Lys9 on H3 (H3K9) was increased in n‐3 deficient DIO mice as compared with control mice, and n‐3 FA in the DIO diet reversed the reduction of H3K4 methylation with no effects on H3K9 methylation. Therefore, epigenetic modification of the leptin promoter region may relate to expressions of leptin and this process may be regulated in part by n‐3 FA.Supported by the Nutricia Research Foundation (2009–15 and 2010‐E4).Grant Funding Source: Nutrition (ASN)