MicroRNA-218 targets adiponectin receptor 2 to regulate adiponectin signaling

Abstract

Adiponectin exerts an antidiabetic function through the adiponectin receptors 1 and 2 (AdipoR1 and AdipoR2). The mechanism regulating the expression of adiponectin receptors remains to be elucidated. Bioinformatics analysis demonstrated that microRNA (miR)-218 targets the 3' untranslated region (3'UTR) of the AdipoR2 mRNA. The present study aimed to investigate whether miR-218 regulated the expression of AdipoR2 using immunoblotting, reverse transcription quantitative polymerase chain reaction and luciferase assays. The protein level and the mRNA level of AdipoR2 were reduced when miR-218 was expressed in HepG2 cells. Additionally, overexpression of miR-218 repressed the activity of a luciferase reporter containing the 3'UTR of AdipoR2. Furthermore, the present study aimed to determine whether miR-218 regulated glucose metabolism through detecting signaling pathways and glucose uptake. The phosphorylation of AMP-activated protein kinase and p38 mitogen-activated protein kinase was reduced in miR-218-expressing cells. In addition, miR-218 inhibited adiponectin-induced glucose uptake. The present results suggested that miR-218 targets AdipoR2 to inhibit adiponectin signaling.