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

FEBS Lett. 2014 Nov 3;588(21):3939-46. doi: 10.1016/j.febslet.2014.09.006. Epub 2014 Sep 19.

Abstract

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.

Keywords: Insulin receptor; Insulin receptor substrate-1; Insulin resistance; MiR-195; MicroRNA; Palmitate; Saturated fatty acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Binding Sites
  • Diet, High-Fat / adverse effects
  • Fatty Acids / pharmacology*
  • Glycogen / metabolism*
  • Hep G2 Cells
  • Hepatocytes / cytology
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Hepatocytes / pathology
  • Humans
  • Insulin / metabolism*
  • Insulin Resistance
  • Mice
  • MicroRNAs / genetics*
  • Obesity / metabolism
  • Obesity / pathology
  • Receptor, Insulin / genetics
  • Signal Transduction / drug effects*
  • Up-Regulation / drug effects

Substances

  • 3' Untranslated Regions
  • Fatty Acids
  • Insulin
  • MIRN195 microRNA, human
  • MIRN195a microRNA, mouse
  • MicroRNAs
  • Glycogen
  • Receptor, Insulin