ORIGINAL RESEARCH article
Front. Nutr.
Sec. Nutrition and Metabolism
Volume 12 - 2025 | doi: 10.3389/fnut.2025.1651993
This article is part of the Research TopicFunctional Foods for Metabolic HealthView all 27 articles
Dietary uridine improves lipid homeostasis in high-fat diet-induced obese mice by regulating liver gene expression and metabolomic profiles
Provisionally accepted
- 1Nanyang Institute of Technology Zhang Zhongjing School of Traditional Chinese Medicine, Nanyang, China
- 2Tianjin Agricultural University, Tianjin, China
- 3Tianjin Academy of Agricultural Sciences, Tianjin, China
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Uridine exerts modulatory effects on lipid metabolism, but the regulatory mechanism in obesity needs further research. 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 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)), and pyrimidine metabolism (uridine phosphorylase 2 (Upp2), ribonucleoside-diphosphate reductase subunit M2 (Rrm2), and thymidine kinase 1 (Tk1)) was improved (P < 0.05). Furthermore, liver metabolomics analysis identified 37 differential metabolites between the HF and HUR groups, primarily enriched in arachidonic acid metabolism and α-linolenic acid metabolism. These findings indicated that uridine supplementation can improve lipid metabolism in obese mice by regulating hepatic gene expression and metabolic pathways.
Keywords: Uridine, Lipid Metabolism, Apoptosis, Metabolomics, Obese mice
Received: 23 Jun 2025; Accepted: 29 Aug 2025.
Copyright: © 2025 Liu, Zhang, Yang and Xie. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Chunyan Xie, Tianjin Academy of Agricultural Sciences, Tianjin, China
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