miR-696 plays a role in hepatic gluconeogenesis in ob/ob mice by targeting PGC-1α.

MicroRNAs (miRNAs or miRs) are known to play a vital role in type 2 diabetes, and peroxisome proliferator-activated receptor-γ (PPARγ) coactivator-1α (PGC-1α) is involved in the pathogenesis of hepatic insulin resistance. However, the correlation, if any, between PGC-1α and miRNAs in the disease has not yet been determined. Thus, in the present study, we aimed to examine the correlation between PGC-1α and miRNAs in diabetes. For this purpose, we used primary hepatocytes isolated from C57BL/6 mice and ob/ob mice. First, we found an inverse correlation between miR‑696 and PGC-1α protein levels in vivo. Second, in vitro evidence demonstrated that PGC-1α expression was significantly decreased by infection with pre-miR‑696-LV, whereas infection with anti-miR‑696-LV increased the PGC-1α protein levels. Third, a luciferase reporter assay confirmed that miR‑696 directly recognizes a specific location within the 3'-untranslated region of PGC-1α transcripts. Furthermore, the biological consequences of miR‑696 targeting PGC-1α were determined by measuring the expression levels of the characteristic hepatic gluconeogenic enzyme, PEPCK, which is regulated by PGC-1α in the liver via the coactivation of transcription factors. Taken together, our findings demonstrate that miR‑696 plays an important role in the development of hepatic gluconeogenesis and insulin resistance through the inhibition of PGC-1α translation in the liver.