MiR-1271 upregulated by saturated fatty acid palmitate provokes impaired insulin signaling by repressing INSR and IRS-1 expression in HepG2 cells.
Dietary saturated fatty acids (SFA) in excess not only induce hepatic insulin resistance, but also result in type 2 diabetes (T2DM). Although microRNAs (miRNAs) participate widely in the pathogenesis of a range of diseases through the suppression of target gene expression at the post-transcriptional level, the implications of SFA-induced miRNAs in the dysregulation of metabolism, particularly in the development of insulin resistance, are largely unclear. SFA palmitate provoked an impairment of insulin signaling in HepG2 cells via a reduction in the expression of INSR and IRS-1 protein. The significant upregulation of miR-1271, which was presumed to target INSR and IRS-1 3'UTRs, was observed in the palmitate-treated HepG2 cells. Using a reporter gene assay, miR-1271 authentically targeted the 3'UTRs of INSR and IRS-1. Furthermore, the overexpression of miR-1271 caused a substantial decrease in INSR and IRS-1 expression, which led to an impairment in insulin signaling and glycogen metabolism. Therefore, these findings suggest that the induction of miR-1271 by SFA palmitate promotes the development of insulin resistance by targeting INSR and IRS-1 in hepatocytes.
Department of Biochemistry, Dongguk University College of Medicine, Gyeongju, 780-714, South Korea.
Won-Mo
WM
Yang
Department of Biochemistry, Dongguk University College of Medicine, Gyeongju, 780-714, South Korea.
Kyung-Ho
KH
Min
Department of Biochemistry, Dongguk University College of Medicine, Gyeongju, 780-714, South Korea; Endocrine Channelopathy, Channelopathy Research Center, Dongguk University College of Medicine, Goyang, 410-773, South Korea. Electronic address: wanlee@dongguk.ac.kr.
Wan
W
Lee
D020413:3' Untranslated Regions / Q000235:genetics; D001483:Base Sequence; D005227:Fatty Acids / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics* / Q000378:metabolism; D007333:Insulin Resistance; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D010168:Palmitates / Q000494:pharmacology*; D011972:Receptor, Insulin / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D015854:Up-Regulation / Q000187:drug effects
D020413:3' Untranslated Regions; D005227:Fatty Acids; C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; C556309:MIRN1271 microRNA, human; D035683:MicroRNAs; D010168:Palmitates; D011972:Receptor, Insulin
INSR; IRS-1; Insulin resistance; Palmitate; Saturated fatty acid; miR-1271; microRNA