Uridine dynamic administration affects the circadian variation of bile acid metabolism in high-fat-diet-fed mice

High-fat diet(HFD)is demonstrated to disturb the bile acid metabolism.The rhythm of bile acid metabolism can also be affected by uridine,whose metabolism exhibits a daily rhythm.However,the mechanism of dynamic uridine administration affecting bile acid during HFD remains unclear.In this study,C57BL/6J mice were fed HFD(the control group;CON)or HFD with oral administration of uridine in the daytime(DUR)and nighttime(NUR)to investigate the mechanism of the effect of uridine on the bile acid.This study showed that the mRNA expression of uridine transporters and circadian clock genes in the jejunum was affected by zeitgeber time(ZT)(P<0.001).Genes related to the metabolism of pyrimidines in the liver showed a high dependence on daily rhythm(P<0.01),and DUR remarkably up-regulated the expression of ribonucleotide reductase regulatory subunit M2(RRM2)(P<0.05)compared to the CON group.Importantly,the mRNA expression of bile acids nuclear receptors,bile acid synthesis,and transporters in the liver showed significantly rhythmically changed(P<0.05),and the expression of cholesterol 7-alpha-hydroxylase(CYP7A1),fibroblast growth factor receptor 4(FGFR4),Na^(+)/taurocholate co transporting polypeptide(NTCP),and bile salt export pump(BSEP)mRNAs of mice with uridine administration increased significantly(P<0.05).The mRNA expression of the transporters of cholesterol and bile acids in the ileum was also affected by ZT(P<0.01)and significantly dependent on uridine administration(P<0.05).The expression of FXR and SHP was significantly affected by ZT and uridine,respectively.In conclusion,dynamic administration of uridine could regulate the rhythm of gene expression of pyrimidine and bile acid metabolism in the liver and ileum of HFD-fed mice,which contributed to the further study of circadian rhythmic physiological and pathological changes of bile acids.

Dietary Eucommia ulmoides leaf extract improves laying performance by altering serum metabolic profiles and gut bacteria in aged laying hens

The leaves of Eucommia ulmoides are rich in bioactive constituents that have potential gastrointestinal benefits for animals.In aged laying hens,intestinal health issues contribute to a significant decline in egg-laying capacity during intermediate and later stages.It remains unclear whether E.ulmoides leaf extract(ELE)can improve intestinal health and enhance egg production in elderly laying hens,and the underlying mechanisms are yet to be elucidated.Therefore,we conducted a study with 480 laying hens(65 weeks old)randomly allocated into four groups:a control group fed with the basal diet,and three treatment groups supplemented with 500,1,000,and 2,000 mg/kg of ELE,respectively.The primary active constituents of ELE include flavonoids,polysaccharides,terpenoids,and phenolic acids.Dietary supplementation with ELE at 1,000 mg/kg(ELE1000)significantly improved laying performance and egg quality compared to the other groups.ELE1000 stimulated the maturation of intestinal epithelial cells,increased villus height,and reduced crypt depth.It also influenced the levels of proteins associated with tight junctions(claudin-1 and claudin-2)and intestinal inflammatory factors(IL-6,IL-1β,and IL-2)in different intestinal sections.Integrative analysis of serum metabolomics and gut microbiota revealed that ELE1000 improved nutrient metabolism by modulating amino acid and ubiquinone biosynthesis and influenced the abundance of intestinal microbiota by enriching pivotal genera such as Bacteroides and Rikenellaceae_RC9_gut_group.We identified 15 metabolites significantly correlated with both gut microbiota and laying performance,e.g.,DL-methionine sulfoxide,THJ2201 N-valerate metabolite,tetracarbonic acid,etc.In conclusion,ELE1000 improved laying performance in elderly laying hens by affecting intestinal morphology,barrier function,microbiota,and serum metabolite profiles.These findings suggest that ELE can be a beneficial feed additive for extending the peak producing period in aged laying hens.