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.

The lack of sophisticated in vitro models limits our current understanding of gastrointestinal functions in farm animals. Conventional 2D cell lines or primary cells fail to recapitulate the physiology of in vivo intestinal epithelium. In contrast stem cell-derived, nontransformed 3D enteroids partially recreate the villus-crypt anatomy of the native intestine and comprise most if not all intestinal cell types including enterocytes, enteroendocrine cells, goblet cells, Paneth cells, and stem cells. This review summarizes the techniques used for generating and culturing enteroids of various farm animal species, focuses on important factors influencing the longevity of enteroids, and provides an overview of their current applications in modeling veterinary pathogens and in developing chemicals and bioactives for treating animal disease and improving production performance. It also mentions current limitations of enteroid models and potential solutions and highlights the opportunities for using these enteroids as a platform in studies regarding veterinary sciences and animal nutrition.

Simple SummaryUridine monophosphate (UMP) and uridine (UR) are rich in sow’s milk. The results from this study showed that UMP and UR affect the lipid profile and lipid metabolism in weanling piglets. It is suggested that UMP and UR improve the energy status in early-weaned piglets.AbstractAs a main ingredient of milk, the nucleotides content is about 12–58 mg/g, which plays a critical role in maintaining cellular function and lipid metabolism. This study was conducted to evaluate the effects of short-term uridine monophosphate (UMP) and uridine (UR) administration on lipid metabolism in early-weaned piglets. Twenty-one weaned piglets (7 d of age; 3.32 ± 0.20 kg average body weight) were randomly assigned into three groups: The control (CON), UMP, and UR group, and oral administered UMP or UR for 10 days, respectively. The results showed that supplementation with UMP significantly increased (p < 0.05) serum low density lipoprotein (LDL) and tended to increase (p = 0.062) serum total cholesterol (TC) content of piglets when compared with the other two groups. Oral administration with UMP and UR significantly decreased (p < 0.05) the serum total bile acid (TBA) and plasma free fatty acids (FFA) of piglets, and significantly reduced the fatty acid content of C12:0 (p < 0.01) and C14:0 (p < 0.05) in liver. Experiments about key enzymes that are involved in de novo synthesis of fatty acid showed that the gene expression of liver X receptors (LXRα), sterol regulatory element-binding transcription factor 1 (SREBP1c), fatty acid desaturase 2 (FADS2), and fatty acid elongase 5 (ELOVL5) were remarkably down-regulated (p < 0.05) with UMP and UR treatment, and key factors of adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), and carnitine palmitoyl transferase 1 (CPT-1α) involved in fatty acid catabolism were also decreased (p < 0.05). Additionally, the protein expression of phosphorylated-mTOR was not affected while phosphorylation of AKT was repressed (p < 0.05). In conclusion, short-term oral UMP or UR administration could regulate fatty acid composition and lipid metabolism, thus providing energy for early-weaned piglets.

The activity of intestinal stem cells (ISCs) is foremost in maintaining homeostasis and repair of intestines. As a pivotal substrate of RNA and DNA biosynthesis, uridine plays essential roles in nutritional and disease monitoring. Whether uridine influences ISC activity remains undefined. To answer this question, 3dimensional (3D) mouse intestinal organoids and living mice were used as a model. It was found that uridine causes a significant decrease in the number of crypts per intestinal organoid. Uridine also significantly decreases mRNA expression and protein levels with markers of ISCs in intestinal organoids in a dose-dependent manner, which was instructed via mTOR. In parallel, uridine decreases the expression of marker of ISCs in mouse intestine in vivo. Our findings are the first to demonstrate that uridine is able to govern the functions of ISCs in intestinal organoid and mouse models. Thus, this study may provide a useful reference for developing novel functional food bioactives that maintain intestinal homeostasis.

No abstract