Uridine inhibits the stemness of intestinal stem cells in 3D intestinal organoids and mice

Liu, Yilin; Guo, Songge; Xie, Changqing; Niu, Kai-Yang; Jonge, Hugo de; Wu, Xin

doi:10.1039/c9ra07742a

Cited by 8 publications

(4 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have demonstrated that maternal dietary supplement UR contributed to reducing the occurrence of diarrhea by regulating cytokine secretion and intestinal mucosal barrier function of suckling pigs [45]. A recent study demonstrated that uridine was able to inhibit stemness of intestinal stem cells in 3D intestinal organoids and mice [46].…”

Section: Relationships Among Uridine and Glucose Lipid And Amino Acmentioning

confidence: 93%

Uridine Metabolism and Its Role in Glucose, Lipid, and Amino Acid Homeostasis

Zhang

Guo

Xie

et al. 2020

BioMed Research International

View full text Add to dashboard Cite

Pyrimidine nucleoside uridine plays a critical role in maintaining cellular function and energy metabolism. In addition to its role in nucleoside synthesis, uridine and its derivatives contribute to reduction of cytotoxicity and suppression of drug-induced hepatic steatosis. Uridine is mostly present in blood and cerebrospinal fluid, where it contributes to the maintenance of basic cellular functions affected by UPase enzyme activity, feeding habits, and ATP depletion. Uridine metabolism depends on three stages: de novo synthesis, salvage synthesis pathway and catabolism, and homeostasis, which is tightly relating to glucose homeostasis and lipid and amino acid metabolism. This review is devoted to uridine metabolism and its role in glucose, lipid, and amino acid homeostasis.

show abstract

Section: Relationships Among Uridine and Glucose Lipid And Amino Acmentioning

confidence: 93%

Uridine Metabolism and Its Role in Glucose, Lipid, and Amino Acid Homeostasis

Zhang

Guo

Xie

et al. 2020

BioMed Research International

View full text Add to dashboard Cite

show abstract

“…As a kind of nucleotide, uridine monophosphate (UMP) represented 98 % of all the monophosphate nucleotides present in the colostrum of sows (6) . Uridine (UR), as a metabolic product of UMP, plays a critical role in regulating energy homoeostasis (11) , protein and lipid metabolism (12,13) . Several studies showed that UR is very important in regulating the metabolism of amino acid and fatty acid, as well as growth performance.…”

mentioning

confidence: 99%

Maternal supplementation with uridine influences fatty acid and amino acid constituents of offspring in a sow–piglet model

et al. 2020

Self Cite

View full text Add to dashboard Cite

Nucleotide plays an important role in the regulation of cellular energy and protein homeostasis. The objective of the current study was to investigate the cumulative effects of maternal supplementation with nucleotides in the form of uridine (UR) on fatty acids and amino acids constituents of neonatal piglets. A total of 52 pregnant sows with similar parity were assigned randomly and equally into the control (CON) group (fed a basal diet) or UR group (fed a basal diet with 150g/t UR). The experiment started on d 85 of gestation and ended on the day of delivery. The reproductive performance was recorded, and placenta, blood and liver samples of neonatal piglets were collected before consuming colostrum during farrowing. Results showed that supplementing with UR in sow’ diet significantly decreased the birth mortality of pigs (P = 0.05). In addition, maternal dietary UR supplementation increased serum total cholesterol (CHOL), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) of neonatal piglets (P < 0.05). Moreover, the amino acid profile of serum and liver of neonatal piglets was affected by the addition of UR in sows’ diets (P<0.05). Furthermore, an up-regulation of mRNA expression of energy metabolism-related genes, including fatty acid elongase 5 (ELOVL5), fatty acid desaturase 1 (FADS1), hormone-sensitive lipase (HSL) and cholesterol- 7a-hydroxylase (CYP7a1), was observed in the liver of neonates from the UR group. Additionally, a decrease in placental gene expression of excitatory amino acid transporters 2 (EAAT2), excitatory amino acid transporters 3 (EAAT3), neutral AA transporter 1(LAT1) in UR group was concurrently observed (P<0.05), and higher protein expression of phosphorylated protein kinase B (P-AKT), raptor, peroxisome proliferator activated receptor α (PPARα) and PPARγ in placenta from UR group was also observed, (P<0.05). Together, these results showed that maternal UR supplementation could regulate the nutrients transport of placenta, largely in response to an alteration of mTORC1-PPARs signaling, thus regulating the nutrition metabolism of neonatal piglets, and improving reproductive performance.

show abstract

“…The expression of genes responsible for nucleotide metabolism is under the control of the circadian clock (Fustin et al, 2012). Uridine, as one of the nucleosides, can stimulate nucleotide transport (Xie et al, 2019), maintain intestinal development (Li et al, 2016), improve the growth performance of suckling piglets and weaned piglets (Li et al, 2019;Wu et al, 2020), and suppress the function of intestinal stem cells (Liu et al, 2020). Importantly, uridine can regulate lipid metabolism (Le et al, 2014a, Le et al, 2014b; short-term uridine administration could prevent drug-induced liver lipid accumulation (Le et al, 2014a), while long-term uridine administration induced severe liver lipid accumulation in mice (Urasaki et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

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

Zhou¹,

ZHANG²,

ZHANG³

et al. 2022

Biocell

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Uridine inhibits the stemness of intestinal stem cells in 3D intestinal organoids and mice

Cited by 8 publications

References 39 publications

Uridine Metabolism and Its Role in Glucose, Lipid, and Amino Acid Homeostasis

Uridine Metabolism and Its Role in Glucose, Lipid, and Amino Acid Homeostasis

Maternal supplementation with uridine influences fatty acid and amino acid constituents of offspring in a sow–piglet model

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

Contact Info

Product

Resources

About