Saturated fatty acids-induced miR-424-5p aggravates insulin resistance via targeting insulin receptor in hepatocytes

Biochemical and Biophysical Research Communications
Kyung-Ho MinWan Lee

Abstract

The excessive intake of saturated fatty acids (SFA) causes obesity and liver steatosis, which are major risk factors for insulin resistance and type 2 diabetes. Although the expression of certain microRNAs (miRNAs) targeting the insulin signaling molecules are regulated aberrantly in SFA-induced obesity, their implications on hepatic insulin resistance are largely unknown. This study examined the associations of miR-424-5p, which is induced by SFA, with the development of insulin resistance. SFA palmitate (PA)-treated HepG2 cells and high fat diet (HFD)-induced obese mouse livers showed an impairment of insulin signaling due to a significant decrease in INSR and IRS-1 expression. Based on expression profiling and qRT-PCR analysis, miR-424-5p, which presumably targets the 3'UTR of INSR, was upregulated in both PA-treated HepG2 cells and the liver of HFD-fed mice. miR-424-5p was found to target the 3'UTR of INSR directly and downregulated INSR expression at the post-transcriptional step. Furthermore, the overexpression of miR-424-5p suppressed INSR expression significantly, leading to impaired insulin signaling and glycogen synthesis in hepatocytes. A novel mechanism for how SFA-induced miR-424-5p impairs insulin signaling throug...Continue Reading

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Citations

Aug 5, 2020·RNA Biology·Juanhong Liu, Feng Liu
Jul 19, 2019·Cell Communication and Signaling : CCS·Yinfang WangPeng Zhang
Nov 25, 2018·International Journal of Molecular Sciences·Laura NigiGuido Sebastiani
Aug 23, 2019·Physiological Reviews·David S Wishart
Dec 5, 2019·Genes·Sandhya PayankaulamDavid N Arnosti
Aug 26, 2020·The Journal of Clinical Endocrinology and Metabolism·Vicente Herrero-AguayoRaúl M Luque
Oct 17, 2020·OncoTargets and Therapy·Shulin LiXiangwei Wang
Jul 19, 2021·Molecular Metabolism·Morris F White, C Ronald Kahn
Dec 1, 2021·Diabetes & Vascular Disease Research : Official Journal of the International Society of Diabetes and Vascular Disease·Elena FlowersBradley E Aouizerat
Jan 6, 2022·Journal of Cachexia, Sarcopenia and Muscle·Lisa DowlingKatarzyna Goljanek-Whysall

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