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

•Saturated fatty acid increases miR-29a and causes insulin resistance in myocytes.•miR-29a directly targets IRS-1 3′UTR and represses IRS-1 expression.•Ectopic expression of miR-29a impairs insulin signaling and glucose uptake.•miR-29a is causally related to the development of insulin resistance by SFA.

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.