Work

Dietary uridine improves lipid homeostasis in high-fat diet-induced obese mice by regulating liver gene expression and metabolomic profiles

Year: 2025

Type: article

Abstract: Introduction Obesity is caused by excessive storage of adipose tissue and leads to metabolic disorders. Uridine exerts modulatory effects on lipid metabolism, but the regulatory mechanism in obesity needs further research. Methods In this study, the effects of uridine supplementation on lipid metabolism were investigated in high-fat diet-induced obese mice. Mice aged at 8 weeks were randomly grouped to receive a control diet (CON, n = 10) or a high-fat diet (HF, n = 24). After 6 weeks of feeding, the HF group was further divided, with half receiving 0.4 mg/mL uridine supplementation in drinking water (HUR, n = 12) for an additional 4 weeks, while the remaining HF mice continued without intervention. Results The results showed that the uridine supplement reduced the liver weight and intra-abdominal white adipose tissue weight in obese mice (p < 0.05). Treatment with uridine and free fatty acid resulted in a significant increase in late and total apoptosis, accompanied by a decrease in early apoptosis of mouse liver organoids (p < 0.05). Moreover, uridine lowered serum levels of triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL), leptin, and liver TG content (p < 0.05). In obese mice fed with uridine, the expression of key genes involved in lipid transport [activated fatty acid translocase/cd36 (Fat/cd36) and low-density lipid receptor (Ldlr)], pyrimidine de novo synthesis [dihydroorotate dehydrogenase (Dhodh)], pyrimidine metabolism [uridine phosphorylase 2 (Upp2), ribonucleoside-diphosphate reductase subunit M2 (Rrm2), and thymidine kinase 1 (Tk1)] was improved (p < 0.05). Furthermore, liver metabolomic analysis identified 37 differential metabolites between the HF and HUR groups, primarily enriched in arachidonic acid metabolism and α-linolenic acid metabolism. Discussion These findings indicated that uridine supplementation can improve lipid metabolism in obese mice by regulating hepatic gene expression and metabolic pathways.

Source: Frontiers in Nutrition

DOI: 10.3389/fnut.2025.1651993

Authors: Yilin Liu, Huihui Zhang, Xudong Yang, Chunyan Xie

Institutions: Nanyang Institute of Technology, Tianjin Agricultural University, Tianjin Academy of Agricultural Sciences

Language: English

Topic: Diet, Metabolism, and Disease

Subfield: Endocrinology, Diabetes and Metabolism

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801