Uridine dynamic administration affects circadian variations in lipid metabolisms in the liver of high-fat-diet-fed...

Carbohydrate and lipid metabolism in the liver has been reported to follow a certain circadian rhythm. Moreover, uridine supplementation also affected glucose and lipid homeostasis in previous studies; however, the mechanisms remain unclear. Therefore, this study was conducted to investigate whether uridine supplementation at an appropriate time during the day can alleviate obesity in mice. C57BL/6J mice were randomly assigned to four groups (n = 24 per group) with different diets for 2 weeks: (1) HFD group, fed a diet containing 60% fat calories; (2) DUR group, fed with HFD supplemented with 400 mg/kg uridine during zeitgeber time (ZT0) 0 - zeitgeber time 12 ZT12; (3) NUR group, fed HFD supplemented with 400 mg/kg uridine during ZT12 - ZT24. Starting at ZT4, liver samples were collected every 6 h for 24 h. Results showed that uridine supplementation, independent of the time of administration during the day, significantly reduced body weight gain (P < .05). Furthermore, liver weight and ratio showed a strong time dependence (P < .001). Additionally, oral administration of uridine during daytime or nighttime changed the expression levels of genes involved in the metabolism of uridine (SLC29A1, UMPS, UPP, UGT1A1, and DHODH; P < .05). Furthermore, uridine affected the levels of 10 fatty acids, lipid and glucose gene (FASN, LCAT, PC, PEPCK, GSK3β, and GLUT2; P < .05) depending on the timing of administration (P < .05). In conclusion, oral supplementation with uridine affected the diurnal variations in liver nucleotide and lipid metabolism, which contributed to the weight loss in HFD-fed mice.