Downregulated microRNA-130b-5p Prevents Lipid Accumulation and Insulin Resistance in a Murine model of Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) amplifies the risk of various liver diseases, ranging from simple steatosis to non-alcoholic steatohepatitis, fibrosis and cirrhosis, and ultimately hepatocellular carcinoma. Accumulating evidence suggests the involvement of aberrant microRNAs (miRNAs or miRs) in the activation of cellular stress, inflammation and fibrogenesis in hepatic cells at different stages of NAFLD and liver fibrosis. Here, we explored the potential role of miR-130b-5p in the pathogenesis of NAFLD, including lipid accumulation and insulin resistance as well as the underlying mechanism. Initially, the expression of miR-130b-5p and insulin like growth factor binding protein 2 (IGFBP2) was examined in the established high-fat diet-induced NAFLD mouse models. Then, the interaction between miR-130b-5p and IGFBP2 was validated using dual-luciferase reporter assay. The effects of miR-130b-5p and IGFBP2 on lipid accumulation and insulin resistance as well as the AKT pathway-related proteins were evaluated using gain- or loss-of-function approaches. miR-130b-5p was upregulated and IGFBP2 was downregulated in liver tissues of NAFLD mice. miR-130b-5p targeted IGFBP2 and downregulated its expression. MiR-130b-5p inhibition or IGFBP2 overexpression reduced the expression of SREBP-1, LXRa, ChREBP, SCD1, ACC1 and FAS, and levels of FBG, FINS and HOMA-IR while increasing the ratio of p-AKT/AKT in NAFLD mice. Overall, downregulation of miR-130b-5p can prevent hepatic lipid accumulation and insulin resistance in NAFLD by activating IGFBP2-dependent AKT pathway, highlighting the potential use of anti-miR-130b-5p as therapeutic approaches for the prevention and treatment of NAFLD.