miR-320 mediates diabetes amelioration after duodenal-jejunal bypass via targeting adipoR1

Background: Duodenal jejunal bypass (DJB) surgery can improve type 2 diabetes (T2D) dramatically. Accumulating evidence implicates deficiency of hepatic adiponectin signaling as a contributor to gluconeogenesis disorders, and some microRNAs (miRNAs) regulate adiponectin receptors (AdipoR1, AdipoR2). We investigated the effects of DJB on hepatic gluconeogenesis, lipid metabolism, and inflammation as well as the effects of miRNA-320 (AdipoR1-targeting miRNA) on DJB-induced T2D amelioration. Objectives: To investigate the essential role of miRNAs in regulation of adiponectin signaling by targeting AdipoRl in DJB and the underlying mechanisms. Setting: University Hospital, China. Methods: We studied hepatic adiponectin signaling changes and hepatic miRNAs involved in a rat model of DJB. We investigated the effects of miR-320 on AdipoR1 signaling in buffalo rat liver cell lines, Liver tissues and glucose tolerance tests were analyzed in DJB rats injected with lentivirus encoding a miR-320 mimic. Results: Transfection with a miR-320 mimic reduced AdipoR1 protein levels and inhibited downstream adiponectin signaling; transfection with a miR-320 inhibitor elicited the opposite effects. A luciferase assay confirmed that miR-320 binds to the 3'-untranslated regions of AdipoR1. Global upregulation of miR-320 expression in DJB rats showed impaired gluconeogenesis, lipid metabolism, and relatively higher expression of inflammation markers. Conclusion: miR-320 regulates the adipoR1-mediated amelioration of T2D in DJB and should be explored as a potential target for T2D treatment. (C) 2018 Published by Elsevier Inc. on behalf of American Society for Metabolic and Bariatric Surgery.