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Published on: October 23, 2018
Uric acid induced hepatocytes lipid accumulation through regulation of miR-149-5p/FGF21 axis
Shenghui Chen1, Dan Chen1, Hua Yang1
1Department of Gastroenterology, the First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, Zhejiang Province, China.
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
