Gestational dietary betaine supplementation suppresses hepatic expression of lipogenic genes in neonatal piglets through epigenetic and glucocorticoid receptor-dependent mechanisms

摘要: Methyl donors play critical roles in nutritional programming through epigenetic regulation of gene expression. Here we fed gestational sows with control or betaine-supplemented diets (3g/kg) throughout the pregnancy to explore effects maternal methyl-donor nutrient on neonatal expression hepatic lipogenic genes. Betaine-exposed piglets demonstrated significantly lower liver triglyceride content associated down-regulated genes acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), stearoyl-CoA desaturase (SCD) and sterol regulatory element-binding protein-1c. Moreover, s-adenosyl methionine homocysteine ratio was elevated betaine-exposed piglets, which accompanied by DNA hypermethylation FAS SCD promoters more enriched repression histone mark H3K27me3 promoter. Furthermore, glucocorticoid receptor (GR) binding promoter diminished along reduced serum cortisol GR protein piglets. GR-mediated confirmed HepG2 cells vitro. Dexamethasone (Dex) drastically increased luciferase activity porcine promoter, while deletion response element attenuated Dex-mediated transactivation. In addition, miR-let-7e, miR-1285 miR-124a, respectively target SCD, ACC GR, were up-regulated being accordance decreased these three Taken together, our results suggest that dietary betaine supplementation during gestation attenuates lipogenesis via mechanisms.