Refeeding with different levels of dietary carbohydrate modulates epigenetic stability through global DNA (de)methylation and histone modifications in juvenile and adult Nile tilapia (Oreochromis niloticus).

The Nile tilapia (Oreochromis niloticus) exhibits a strong metabolic response to dietary carbohydrates (CHO). Short-term refeeding after fasting with a high-carbohydrate (HC) diet has been shown to modulate CHO metabolism, but the role of epigenetic regulation in this response remains unclear. This study investigated how short-term refeeding with either a HC [639.2 g kg(-1) diet]/low-protein [164.9 g kg(-1) diet] (HC/LP) diet or a low-CHO [47.4 g kg(-1) diet]/high-protein [607.9 g kg(-1) diet] (LC/HP) diet influences global DNA methylation and demethylation, histone modifications, and mRNA levels of epigenetic regulators in the liver and muscle of juvenile and adult Nile tilapia. Following a 4-day fasting period, fish were refed for 4 days with either HC/LP or LC/HP diets. Compared to the fasted state, refeeding with either diet altered epigenetic markers by: (1) decreasing hepatic global DNA 5-mC oxidative derivatives-5-hmdC in juveniles, and both 5-hmdC and 5-cadC in adults; (2) inducing histone hypermethylation and/or hyperacetylation - H3K9ac (hepatic) and H3K36me3 (muscular) in juveniles, and H3K9me3 and H3K9ac (muscular) in adults; and (3) promoting expression of enzymes related to DNA hypermethylation (upregulated dnmt, downregulated tet) and histone hypermethylation/acetylation (upregulated setd1b, kmt2, suv39h1b; downregulated kdm4, sirt5). Diet-specific effects included hepatic H3K36 hypomethylation and H3K9 hypoacetylation in juveniles fed HC/LP, accompanied by upregulation of kdm4b, kdm4c, and sirt5. In adults, HC/LP refeeding induced muscular DNA hypomethylation and H3K9 hypoacetylation, associated with upregulation of tet, sirt2, and sirt5. Refeeding following fasting induced histone hypermethylation and/or hyperacetylation, while HC refeeding was particularly associated with muscular global DNA hypomethylation and histone hypoacetylation/methylation.