Induction of miR-29a by saturated fatty acids impairs insulin signaling and glucose uptake through translational repression of IRS-1 in myocytes.
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.
Department of Biochemistry, Dongguk University College of Medicine, Gyeongju 780-714, Republic of Korea.
Won-Mo
WM
Yang
Department of Biochemistry, Dongguk University College of Medicine, Gyeongju 780-714, Republic of Korea.
Hyo-Jin
HJ
Jeong
Department of Biochemistry, Dongguk University College of Medicine, Gyeongju 780-714, Republic of Korea.
Seung-Yoon
SY
Park
Department of Biochemistry, Dongguk University College of Medicine, Gyeongju 780-714, Republic of Korea; Endocrine Channelopathy, Channelopathy Research Center, Dongguk University College of Medicine, Goyang 410-773, Republic of Korea. Electronic address: wanlee@dongguk.ac.kr.
Wan
W
Lee
D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D059305:Diet, High-Fat; D005227:Fatty Acids / Q000378:metabolism / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics*; D007333:Insulin Resistance; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D019308:Palmitic Acid / Q000378:metabolism / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
D020413:3' Untranslated Regions; D005227:Fatty Acids; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; C547014:MIRN29 microRNA, mouse; D035683:MicroRNAs; D019308:Palmitic Acid; D005947:Glucose
IRS-1; Insulin resistance; MicroRNA; Palmitate; Saturated fatty acid; miR-29a