Induction of miR-29a by saturated fatty acids impairs insulin signaling and glucose uptake through translational repression of IRS-1 in myocytes

FEBS Lett. 2014 Jun 13;588(13):2170-6. doi: 10.1016/j.febslet.2014.05.011. Epub 2014 May 17.


MicroRNAs have been shown to play an important role in insulin signaling but their biological function in insulin resistance induced by saturated fatty acids (SFA) remains largely unknown. Here, we report that SFA palmitate and high fat diet (HFD) significantly increase expression of miR-29a in myocytes. miR-29a targets IRS-1 3'UTR directly and represses IRS-1 expression at the translational level. Furthermore, the ectopic expression of miR-29a impairs insulin signaling and glucose uptake in myocytes through a substantial decrease in IRS-1. These findings suggest that the up-regulation of miR-29a by SFA is causally related to the development of insulin resistance in myocytes.

Keywords: IRS-1; Insulin resistance; MicroRNA; Palmitate; Saturated fatty acid; miR-29a.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Base Sequence
  • Cell Line
  • Diet, High-Fat
  • Fatty Acids / metabolism
  • Fatty Acids / pharmacology*
  • Glucose / metabolism*
  • Insulin / metabolism*
  • Insulin Receptor Substrate Proteins / genetics*
  • Insulin Resistance
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics*
  • Muscle Fibers, Skeletal / drug effects*
  • Muscle Fibers, Skeletal / metabolism*
  • Palmitic Acid / metabolism
  • Palmitic Acid / pharmacology
  • Protein Biosynthesis / drug effects
  • Signal Transduction / drug effects
  • Up-Regulation / drug effects


  • 3' Untranslated Regions
  • Fatty Acids
  • Insulin
  • Insulin Receptor Substrate Proteins
  • Irs1 protein, mouse
  • MIRN29 microRNA, mouse
  • MicroRNAs
  • Palmitic Acid
  • Glucose