Saturated fatty acid-induced miR-195 impairs insulin signaling and glycogen metabolism in HepG2 cells

•Saturated fatty acid (SFA) up-regulates miR-195, and causes insulin resistance in HepG2 cells.•MiR-195 is increased in the liver of high fat diet (HFD)-induced hyperglycemic mice.•MiR-195 directly suppresses the expression of INSR by targeting the INSR-3′UTR.•Ectopic expression of miR-195 impairs insulin signaling and glycogen synthesis.•MiR-195 is causally linked to the development of insulin resistance by SFA. MicroRNAs (miRNAs) play an important role in insulin signaling and insulin secretion, but the role of miRNAs in the association between obesity and hepatic insulin resistance is largely unknown. This study reports that saturated fatty acid (SFA) and high fat diet (HFD) significantly induce miR-195 expression in hepatocytes, and that the insulin receptor (INSR), not insulin receptor substrate-1 (IRS-1), is a direct target of miR-195. Furthermore, the ectopic expression of miR-195 suppresses the expression of INSR, thereby impairing the insulin signaling cascade and glycogen synthesis in HepG2 cells. These findings suggest that the dysregulation of miR-195 by SFA is a detrimental factor for hepatic insulin sensitivity.