Novel mechanisms of dietary folic acid in improving hepatopancreas health of grass carp (Ctenopharyngodon idellus): the perspectives of autophagy and DNA methylation.

B vitamins play an important role in improving lipid and glucose metabolism in fish, but there remains a lack of systematic and in-depth research on the effects of folic acid (FA) on lipid and glucose metabolism in the hepatopancreas of fish. This study aims to investigate the effects of dietary FA on lipid and glucose metabolism in the hepatopancreas of grass carp and the potential molecular mechanisms. The 450 healthy grass carp (686.83 ± 1.31 g) were randomly divided into 18 barrels, and fed diets containing levels of FA (0.57, 1.11, 1.53, 2.08, 2.64 and 3.15 mg/kg diet) for 8 weeks. The results showed that the appropriate level of dietary FA significantly up-regulated the protein expression of GLUT2, G6PD and p-AKT, down-regulated the protein expression of PCK1. Meanwhile, dietary FA significantly reduced the area of lipid droplets in hepatopancreas, up-regulated the protein expression of PPARα, and down-regulated the protein expression of PPARγ. In addition, our results demonstrated that dietary FA supplementation up-regulated the protein levels of LAMP1, LC3B and PLIN2. Finally, dietary FA significantly increased the ratio of SAM/SAH in the hepatopancreas, up-regulated the protein expression of MTHFR and DNMT3A, as well as the nuclear translocation of TFEB. In summary, based on the present findings, dietary FA may improve glucose metabolism through the AKT signaling pathway, and appears to alleviate hepatopancreas lipid accumulation through one-carbon metabolism-dependent DNA methylation and the TFEB-mediated autophagy pathway.