Effect Of Uridine Supplementation On Glycolipid Metabolism In C57BL/6J Mice Under Different Dietary Conditions

The purpose of this study was to investigate the effects of uridine on glucose and lipid metabolism in mice under different dietary status(basal and high fat diets).This experiment was a two-factor design,32 female C57BL/6J mice with 7 weeks of age were selected in this experiment.After one week adaptation,they were randomly divided into 4 groups by weight,with 8 repetitions in each group,basal diet(BD),basal diet supplemented with 0.1% uridine(BD+UR),high fat diet(HFD),and high fat diet supplemented with 0.1% uridine(HFD+UR),respectively.The experiment was conducted for a month and blood was taken from the eyeball.In addition,the liver and ileum tissues were also collected.The indexes related glycolipid metabolism were determined in serum and liver.The expression of genes related glycolipid metabolism and proteins related energy metabolism were detected in the organization.The experimental results were listed as follows:(1)Compared with the basal diet,the high fat diet significantly increased the weight gain and liver index(P<0.05)in mice,but uridine supplementation in high fat diet significantly reduced the liver index of mice.(2)There was a high fat × uridine interaction effect in serum glucose(GLU)and liver cholesterol(TC)(P<0.05).Supplementation of uridine in different dietary status had different effects on serum GLU and liver TC.Supplementation of uridine in basal diet significantly increased serum GLU and liver TC content.However,supplementation of uridine in high fat diet significantly reduced serum GLU and liver TC content(P<0.05).Compared with basal diet,high-fat diet significantly increased serum TG and liver TC and reduced serum HDL and LDL content(P<0.05).(3)Compared with basal diet,high-fat diet significantly reduced the mRNA expression of SLC28A2 gene in ileum(P<0.05).Furthermore,supplementation of uridine in high fat diet significantly increased the mRNA expression of SLC29A2 and SLC28A2 genes in ileum(P<0.05).(4)There was a high fat × uridine interaction effect in the expression of FASN,SHP and Cyp7?1 genes related to lipid metabolism in liver(P<0.01).Supplementation of uridine in high fat diet significantly reduced the expression of FOXO1 and PEPCK genes,and supplementation of uridine in basal diet significantly reduced the expression of GS and PEPCK genes(P<0.05).Supplementation of uridine in different diets had different effects on the mRNA expression of genes related lipid metabolism in the liver.In high fat diet,the mRNA expression of FASN and SHP genes were significantly reduced and the mRNA expression of Cyp7?1 gene was significantly increased by uridine supplementation.Compared with basal diet,high-fat diet significantly up-regulated the mRNA expression of SHP gene and down-regulated the mRNA expression of HMGCR and Cyp7?1 genes(P<0.05).(5)There was a high fat × uridine interaction effect in the mRNA expression of ABCG5,ABCG8 related cholesterol excretion genes and MTP gene related lipid transporter in ileum(P<0.05).Supplementation of uridine significantly reduced the mRNA expression of ABCG5 gene in basic diet and significantly increased the mRNA expression of ABCG8 gene in high fat diet(P<0.05).Supplementation of uridine in different diet had different effects on the mRNA expression of MTP gene.The mRNA expression of MTP gene was significantly reduced by uridine supplementation in basal diet,but was increased significantly by uridine supplemented in high fat diet(P<0.05).High fat also affected the mRNA expression of ABCA1 and FGF15 genes(P<0.05).Compared with basal diet,high fat diet significantly up-regulated the mRNA expression of these genes(P<0.05).(6)Compared with basal diet,high fat diet significantly increased the phosphorylation of mTOR protein and uridine supplementation in basal diet and high fat diet significantly increased the phosphorylation of mTOR and AMPK ?1/2 proteins(P<0.05),respectively(P<0.05).In summary,the results showed that:(1)In different dietary status,uridine might affect liver glucose and lipid metabolism by affecting the AMPK and mTOR signaling pathways.Uridine supplementation in basal and high fat diets could reduce gluconeogenesis in the liver,but supplementation of uridine in different dietary had different effects on liver lipid metabolism.Supplementation of uridine in basal diet increased fat synthesis and reduced bile acid synthesis,while supplementation of uridine in high fat diet had opposite effects.(2)In the high fat diet state,uridine enhanced the mRNA expression of nucleoside transporter in ileum,reduced the absorption of cholesterol to the ileum and increased the excretion of cholesterol in ileum,thereby reducing the accumulation of cholesterol in the liver,while supplementation of uridine in the basal diet increased the absorption of cholesterol to the ileum and reduced the excretion of cholesterol in ileum leading to the accumulation of cholesterol in the liver.