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- Title
Uric acid induced hepatocytes lipid accumulation through regulation of miR-149-5p/FGF21 axis.
- Authors
Chen, Shenghui; Chen, Dan; Yang, Hua; Wang, Xinyu; Wang, Jinghua; Xu, Chengfu
- Abstract
<bold>Background: </bold>Hyperuricemia is a major risk for non-alcoholic fatty liver disease. However, the mechanisms for this phenomenon are not fully understood. This study aimed to investigate whether microRNAs mediated the pathogenic effects of uric acid on non-alcoholic fatty liver disease.<bold>Methods: </bold>Microarray was used to determine the hepatic miRNA expression profiles of male C57BL/6 mice fed on standard chow diet, high fat diet (HFD), and HFD combined with uric acid-lowering therapy by allopurinol. We validated the expression of the most significant differentially expressed microRNAs and explored its role and downstream target in uric acid-induced hepatocytes lipid accumulation.<bold>Results: </bold>Microarray analysis and subsequent validation showed that miR-149-5p was significantly up-regulated in the livers of HFD-fed mice, while the expression was down-regulated by allopurinol therapy. MiR-149-5p expression was also significantly up-regulated in uric acid-stimulated hepatocytes. Over-expression of miR-149-5p significantly aggregated uric acid-induced triglyceride accumulation in hepatocytes, while inhibiting miR-149-5p ameliorated the triglyceride accumulation. Luciferase report assay confirmed that FGF21 is a target gene of miR-149-5p. Silencing FGF21 abolished the ameliorative effects of miR-149-5p inhibitor on uric acid-induced hepatocytes lipid accumulation, while overexpression of FGF21 prevented the lipid accumulation induced by miR-149-5p mimics.<bold>Conclusions: </bold>Uric acid significantly up-regulated the expression of miR-149-5p in hepatocytes and induced hepatocytes lipid accumulation via regulation of miR-149-5p/FGF21 axis.
- Subjects
URIC acid; FATTY liver; HIGH-fat diet; LIPIDS; RNA metabolism; THERAPEUTIC use of antimetabolites; TRIGLYCERIDES; HYPERURICEMIA; BIOCHEMISTRY; GROWTH factors; ALLOPURINOL; ANIMAL nutrition; PHENOMENOLOGY; RESEARCH funding; EPITHELIAL cells; OXIDOREDUCTASES; ANIMALS; MICE; ENZYME inhibitors; CHEMICAL inhibitors; DISEASE complications
- Publication
BMC Gastroenterology, 2020, Vol 20, Issue 1, p1
- ISSN
1471-230X
- Publication type
journal article
- DOI
10.1186/s12876-020-01189-z