Obesity-Induced Upregulation of microRNA-183-5p Promotes Hepatic Triglyceride Accumulation by Targeting the B-Cell Translocation Gene 1

Background: Obesity is recognized as a risk factor for many metabolic disorders, particularly nonalcoholic fatty liver disease (NAFLD). However, the underlying mechanism is still poorly understood. Several lines of evidence indicate that microRNA (miRNA) is a key regulator of lipid metabolism. In this study, we investigated the role of miR-183-5p in the development of NAFLD. Methods: The expression levels of miR-183-5p and B-cell translocation gene 1 (Btg1) were determined by quantitative real-time PCR and histological analysis in livers of obese mice and cell models induced with palmitic acid (PA), respectively. AML12 cells were treated with PA in the presence or absence of miR-183-5p mimics or inhibitor. Moreover, a Luciferase reporter assay was used to determine whether Btg1 is the direct target of miR-183-5p. Protein levels of BTG1 were estimated using western blotting. Findings: Expression of miR-183-5p was increased in the livers of three murine models and also in the AML12 cell model. Overexpression of miR-183-5p in the cell model and mice led to hepatic triglyceride (TG) accumulation and upregulation of lipogenic genes, whereas inhibition of miR-183-5p in the cell model improved hepatic TG accumulation. Mechanistically, we further identified Btg1 as a direct target gene of miR-183-5p. Btg1 was lowly expressed in obese livers, and Btg1 expression was negatively correlated with the miR-183-5p level in AML12 cell model and liver model. Interpretation: Our findings revealed that miR-183-5p affected the regulation of hepatic TG homeostasis, which may provide a potential therapeutic target for hepatosteatosis. Funding Statement: This work was funded the grants from the Natural Science Foundation and Key-Area Research and Development Program of Guangdong Province (Nos.2018B030311031 and 2019B020227004). Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: The Animal Care Committee approved all animal protocols of the School of Medicine, Xiamen University, and the study adhered to the criteria outlined in the "Guide for the Care and Use of Laboratory Animals."