miR-23a/b-3p promotes hepatic lipid accumulation by regulating Srebp-1c and Fas

J Mol Endocrinol. 2021 Nov 26;68(1):35-49. doi: 10.1530/JME-20-0324.

Abstract

miR-23a-3p and miR-23b-3p are members of the miR-23~27~24-2 superfamily. The role of miR-23a/b-3p in regulating hepatic lipid accumulation is still unknown. Here, we found that increased miR-23a-3p and miR-23b-3p levels were accompanied by an increase in the protein levels of the sterol regulatory element-binding protein-1 (SREBP-1) and fatty acid synthase (FAS) in the steatotic livers of mice fed a high-fat diet and leptin receptor-deficient type 2 diabetic mice (db/db). Importantly, overexpression of miR-23a/b-3p in Hep1-6 cells elevated the intracellular triglyceride level and upregulated the expression of Srebp-1c and Fas. Taken together, these results suggested that miR-23a/b-3p enhanced mRNA stability by binding the 5'-UTR of Srebp-1c and Fas mRNA, thereby promoting triglyceride accumulation in hepatocytes.

Keywords: 5'-UTR; Fas; Srebp-1c; miR-23a/b-3p; triglyceride accumulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions
  • Animals
  • Diet, High-Fat
  • Disease Susceptibility
  • Fatty Acid Synthase, Type I / genetics*
  • Fatty Acid Synthase, Type I / metabolism
  • Gene Expression Regulation*
  • Hepatocytes / metabolism
  • Lipid Metabolism*
  • Liver / metabolism*
  • Male
  • Mice
  • MicroRNAs / genetics*
  • Non-alcoholic Fatty Liver Disease / etiology
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Non-alcoholic Fatty Liver Disease / pathology
  • RNA Interference
  • Sterol Regulatory Element Binding Protein 1 / genetics*
  • Sterol Regulatory Element Binding Protein 1 / metabolism
  • Triglycerides / metabolism

Substances

  • 5' Untranslated Regions
  • MicroRNAs
  • Mirn23b microRNA, mouse
  • Sterol Regulatory Element Binding Protein 1
  • Triglycerides
  • Fasn protein, mouse
  • Fatty Acid Synthase, Type I