Effects And Mechanism Of Uridine Supplementation On Lipid Metabolism In Maternal And Offspring Mice Under High-fat Diet During Pregnancy And Lactation

Obesity has become one of the most rigorous public health problems in the world,and for newborn life,maternal overnutrition during pregnancy is one of the main reasons for its obesity.The content of nucleotides in milk is very high,of which uridine monophosphate accounts for the highest proportion,and uridine is the precursor of uridine monophosphate.Accumulated studies have shown that uridine can regulate lipid metabolism in the liver and alleviate obesity caused by high fat diet.However,it is unclear whether uridine will affect the lipid metabolism of the offspring mice through the maternal mice.Therefore,the purpose of this study was to study the effects and mechanism of uridine supplementation on lipid metabolism in maternal and the offspring mice under high-fat diet during pregnancy and lactation.In this study,8-week-old female and male mice were bred after 2 weeks of adaptation and according to the ratio of 2:1.Forty-five mice pregnant 7-days were randomly divided into three groups(n=15),a control group,a high-fat group,and a high-fat uridine supplemented group(uridine supplemented with 400 mg/kg body weight/d),respectively.After the maternal mice were delivered,the liver of the neonatal mice was collected,and after 21 days of weaning,the serum and liver of the weaned mice and the serum and liver tissue of the maternal mice were collected.Finally analyzed all samples in the laboratory.The main results are as follows:(1)The results of maternal mice showed that high-fat diet increased the body weight and mesenteric fat coefficient of the ICR maternal mice,increased the levels of GLU,TG,TC,HDL and LDL in the serum,and significantly reduced the expression of Lxr?,Cyp27a1,Fxr and Shp in the liver(P<0.05).Uridine supplementation reduced the mesenteric fat coefficient of the maternal mice,increases the subcutaneous fat coefficient,reduces the content of TG,TC,HDL,LDL and TBA in the serum,and significantly reduces the relative expression of Acc and Fat/cd36 in the liver of maternal mice(P<0.05).(2)Results of neonatal mice showed that the feeding of high-fat diets during pregnancy reduced the number of newborn mice and increased their weight.In addition,high fat diet significantly reduced the expression of Fat/cd36 in the liver of ICR newborn mice,and significantly increased the expression of Cyp27a1(P<0.05);while uridine supplementation significantly increased the expression of Fat/cd36 and significantly reduced the expression of Hmgcr,Lxr? and Cyp27a1 in the liver of neonatal mice(P<0.05).(3)Results of weaned mice showed that high-fat diet during pregnancy and lactation significantly increased the body weight of weaned mice(P<0.05).A high-fat diet significantly increased the content of glucose in the serum of weaned-male mice and significantly reduced the content of total bile acids in the serum of weaned-male mice(P<0.05).The results of liver gene expression in weaned-female mice showed that high fat significantly reduced the expression of Fasn,Acc,Cyp7a1 and Shp in the liver,and significantly increased the expression of Cpt1a,Cyp27a1 and Cyp8b1(P<0.05);urine supplementation under high-fat diet significantly down-regulated the expression levels of Cpt1a,Cyp27a1 and Cyp8b1,and significantly up-regulated the expression level of Cyp7a1(P<0.05).The results of liver gene expression in weaned-male mice showed that high fat significantly reduced the expression of Fasn,Acc,Hmgcr and Shp,and significantly increased the expression of Cyp8b1(P<0.05).High fat diet and supplemented with uridine significantly decreased the expression of Ppar?,Hmgcr and Cyp8b1(P<0.05).(4)RNA sequencing results showed that uridine supplementation significantly changed the expression of 193 genes in the liver of maternal mice,and increased the expression of 135 genes and down-regulated the expression of 58 genes.Uridine has effect on Toll-like receptor signaling pathway and intestinal immune network for IgA production signaling pathway,besides,uridine administration also has influences on the signaling pathways of pyrimidine metabolism and the conversion of pentose and glucuronate.(5)RNA sequencing results showed that uridine supplementation significantly changed the expression of 243 genes in the liver of neonatal mice.Uridine supplementation increased 132 genes and down-regulated 111 genes.The pathways involved in these genes are the metabolism of linoleic acid and arachidonic acid,the metabolism of retinol and cholesterol,and the biosynthesis of steroid hormones.