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 different 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 glucose transporter 2, glucose-6-phosphate dehydrogenase, and phosphorylated protein kinase B and down-regulated the protein expression of phosphoenolpyruvate carboxykinase 1. Meanwhile, dietary FA significantly reduced the area of lipid droplets in hepatopancreas, up-regulated the protein expression of peroxisome proliferators-activated receptor α, and down-regulated the protein expression of peroxisome proliferators-activated receptor γ. In addition, our results demonstrated that dietary FA supplementation up-regulated the protein levels of lysosomal-associated membrane protein 1, microtubule-associated protein light chain 3 beta, and perilipin 2. Finally, dietary FA significantly increased the ratio of S-Adenosylmethionine/S-Adenosylhomocysteine in the hepatopancreas, up-regulated the protein expression of 5,10-methylenetetrahydrofolate reductase and DNMT3A, as well as the nuclear translocation of transcription factor EB. In summary, based on the present findings, dietary FA may improve glucose metabolism through the protein kinase B signaling pathway, and appears to alleviate hepatopancreas lipid accumulation through one-carbon metabolism-dependent DNA methylation and the transcription factor EB-mediated autophagy pathway.