Effects Of Dietary Supplementation Of 5-MTHF On Lipid Metabolism In The Liver Of MTHFR Gene-silenced Mice

Folic acid is an essential vitamin for mammals.It participates in various metabolisms of the body,regulates the diversity of intestinal flora,promotes gastrointestinal health,and improves the reproductive traits and production performance of animals.5-Methyltetrahydrofolate（5-MTHF）,the active form of folic acid,is involved in one-carbon metabolism in the liver in the body.Methylenetetrahydrofolate reductase（MTHFR）is a key enzyme in the production of 5-MTHF.Disruption of one-carbon metabolism can impair the antioxidant capacity of nutrients,resulting in liver damage and abnormal lipid metabolism.In this study,based on the perspective of one-carbon unit metabolism,MTHFR gene-silenced mice were used as model animals to reveal the effects of dietary supplementation of 5-MTHF on liver injury and lipid metabolism,and provide a theoretical basis for dietary supplementation of folic acid to regulate one-carbon metabolism and improve liver injury and lipid metabolism.Silencing of the MTHFR gene causes liver injury and abnormal lipid metabolism in mice: The liver tissue of Mthfr^+/-genotype mice was abnormal in structure,some hepatocytes were mildly steatotic,and a few small lipid droplets appeared in the cytoplasm.The liver tissue of Mthfr^+/-genotype mice supplemented with synthetic folic acid（FA）had inflammatory cell infiltration,while the Mthfr^+/-genotype mice supplemented with 5-MTHF showed no inflammatory cell infiltration.The triglyceride content in the liver of Mthfr^+/-genotype mice supplemented with 5-MTHF in the diet was lower than that of the FA supplemented group.It indicated that MTHFR gene silencing caused triglyceride accumulation,hepatic steatosis and inflammatory response,resulting in liver injury and abnormal lipid metabolism.5-MTHF can alleviate liver injury and abnormal lipid metabolism caused by MTHFR gene silencing,and its effect is better than FA.Supplementation of 5-MTHF increases folate concentrations in serum and liver of Mthfr^+/-mice: Supplementation of 5-MTHF in the diet increased the content of FA and 5-MTHF in the serum and liver of mice,and decreased the level of hepatic Hcy.5-MTHF significantly increased the content of SAM and SAH in the liver of Mthfr^+/-mice.It shows that the ability of 5-MTHF to increase blood folic acid concentration is higher than that of synthetic folic acid.Supplementation of 5-MTHF regulates one-carbon metabolism in the liver of Mthfr^+/-mice: Dietary supplementation of 5-MTHF decreased the expression of Mthfd1,AHcy and Bhmt1 genes in the liver of Mthfr^+/-genotype mice,and increased the expression of Shmt1 gene.It indicated that silencing the Mthfr gene changed the one-carbon metabolism involved in folic acid.There are some functional differences between the two forms of FA and 5-MTHF.Supplementation of 5-MTHF regulates lipid metabolism in the liver of Mthfr^+/-mice: 5-MTHF significantly increased the m RNA expression levels of lipoprotein,lipid metabolism and phospholipid transfer protein Nr1h4 in mice liver,and decreased the level of Srebf1 c,a gene involved in fatty acid synthesis.This indicated that 5-MTHF could improve the abnormal lipid metabolism caused by MTHFR gene silencing.In conclusion,MTHFR gene silencing leads to liver injury and abnormal lipid metabolism.5-MTHF can improve the utilization rate of folic acid,regulate the one-carbon metabolism involved in folic acid,relieve and improve the liver injury and abnormal lipid metabolism caused by MTHFR gene silencing.