Circadian rhythmicity, the ability of most organisms to adapt to the environment, plays a major role in orchestrating daily physiology. Carbohydrate and lipid metabolism in the liver has been reported to follow a certain circadian rhythm.  

Uridine, a uracil nucleoside, has a role in nutrient availability, adipocyte function, and cellular energy homeostasis. According to previous studies, uridine supplementation also affected glucose and lipid homeostasis, but the mechanisms remain unclear. 

Researchers from the Institute of Subtropical Agriculture (ISA) of the Chinese Academy of Sciences conducted a two-week experiment to determine the effects of high-fat-diet (HFD) and concomitant uridine supplementation at different times throughout the day on liver lipid and glucose metabolism in C57BL/6J mice. 

This study showed that uridine supplementation, independent of the time of administration during the day, significantly reduced body weight gain (P<0.05). Furthermore, liver weight and ratio showed a strong time dependence (P<0.001).  

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<0.05). Furthermore, uridine affected the levels of 10 fatty acids, lipid and glucose gene (FASN, LCAT, PC, PEPCK, GSK3β, and GLUT2; P<0.05) depending on the timing of administration (P<0.05).  

Oral supplementation with uridine affected the diurnal variations in liver nucleotide and lipid metabolism, which contributed to the weight loss in HFD-fed mice. 

The study, published in Chronobiology International, was supported by the National Key R&D Program of China, the STS Program of Chinese Academy of Sciences, CAS President’s International Fellowship for Visiting Scientists.