Open Access

ARTICLE

Uridine dynamic administration affects the circadian variation of bile acid metabolism in high-fat-diet-fed mice

by TIANTIAN ZHOU^1,3,#, YUMEI ZHANG^1,2,#, JUAN ZHANG^1,2, CHUNYAN XIE², ZHENYA ZHAI^1,2, XIN WU^1,2,3,*

1 CAS Key Laboratory of Agri-Ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, the Chinese Academy of Sciences, Hunan Provincial Engineering Research Center for Healthy Livestock and Poultry Production, Changsha, 410125, China
2 Institute of Biological Resources, Jiangxi Academy of Sciences, Nanchang, 330096, China
3 University of Chinese Academy of Sciences, Beijing, 100049, China

* Corresponding Author: XIN WU. Email:
# These authors contributed equally to this work.

BIOCELL 2022, 46(11), 2433-2442. https://doi.org/10.32604/biocell.2022.021290

Received 06 January 2022; Accepted 11 April 2022; Issue published 07 July 2022

Abstract

High-fat diet (HFD) is demonstrated to disturb the bile acid metabolism. The rhythm of bile acid metabolism can also be affected by uridine, whose metabolism exhibits a daily rhythm. However, the mechanism of dynamic uridine administration affecting bile acid during HFD remains unclear. In this study, C57BL/6J mice were fed HFD (the control group; CON) or HFD with oral administration of uridine in the daytime (DUR) and nighttime (NUR) to investigate the mechanism of the effect of uridine on the bile acid. This study showed that the mRNA expression of uridine transporters and circadian clock genes in the jejunum was affected by zeitgeber time (ZT) (P < 0.001). Genes related to the metabolism of pyrimidines in the liver showed a high dependence on daily rhythm (P < 0.01), and DUR remarkably up-regulated the expression of ribonucleotide reductase regulatory subunit M2 (RRM2) (P < 0.05) compared to the CON group. Importantly, the mRNA expression of bile acids nuclear receptors, bile acid synthesis, and transporters in the liver showed significantly rhythmically changed (P < 0.05), and the expression of cholesterol 7-alpha-hydroxylase (CYP7A1), fibroblast growth factor receptor 4 (FGFR4), Na+/taurocholate co transporting polypeptide (NTCP), and bile salt export pump (BSEP) mRNAs of mice with uridine administration increased significantly (P < 0.05). The mRNA expression of the transporters of cholesterol and bile acids in the ileum was also affected by ZT (P < 0.01) and significantly dependent on uridine administration (P < 0.05). The expression of FXR and SHP was significantly affected by ZT and uridine, respectively. In conclusion, dynamic administration of uridine could regulate the rhythm of gene expression of pyrimidine and bile acid metabolism in the liver and ileum of HFD-fed mice, which contributed to the further study of circadian rhythmic physiological and pathological changes of bile acids.

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