MicroRNA-199a-3p attenuates hepatic lipogenesis by targeting Sp1

Emerging studies have demonstrated that microRNAs (miRs) are profoundly involved in non-alcoholic fatty liver disease (NAFLD) and related metabolic diseases. Previously, we revealed a repertoire of miRs dysregulated in NAFLD by high-throughput sequencing. Here, we showed that microRNA-199a-3p was down-regulated in the livers of C57BL/6J mice fed a high-fat-diet (HFD) and oleic acid/palmitic acid-induced Hepa1-6 cells. Gain-of-function and loss-of-function studies demonstrated that microRNA-199a-3p exhibited a suppressive role in hepatic lipogenesis. Adenoviral mediated microRNA-199a-3p expression in C57BL/6J mice largely attenuated triglyceride (TG) accumulation and expression of lipogenic genes. Furthermore, we identified Specificity Protein 1 (Sp1) as the functional target of miR-124. Restoration of Sp1 expression largely compromised the effect of microRNA-199a-3p on hepatic TG metabolism. Taken together, our findings uncover a novel function of microRNA-199a-3p/Sp1 axis in NAFLD and provide a mechanism underlying perturbations of hepatic TG homeostasis.