miR-182-5p Attenuates High-Fat -Diet-Induced Nonalcoholic Steatohepatitis in Mice

Ann Hepatol. 2019 Jan-Feb;18(1):116-125. doi: 10.5604/01.3001.0012.7902.

Abstract

Introduction and aim: Patients with NASH have increased risk for sepsis or cardiovascular disease after Liver transplantation. An important role of Toll-like receptor (TLR) 4 in the pathogenesis of nonalcoholic steatohepatitis (NASH) was demonstrated. Here, we study the role of miR-182-5p in TLR4 expression and high-fat-diet (HFD)-induced NASH in vitro and in vivo Material and methods. Following transfection with a miR-182-5p mimic, the effect of miR-182-5p on TLR4 in RAW264.7 and HepG2 cells was investigated. Following administration of the miR-182-5p mimic into the livers of HFD-induced NASH mice, we determined the in vivo expression of TLR4, TNFa, and IL-6 and assessed the histologic features of the livers. Results Following lipopolysaccharide (LPS) treatment of RAW264.7 cells, real-time RT-PCR and western blot results indicated decreases levels of TLR4 mRNA and protein in the miR-182-5p group as compared with levels observed in controls, with similar trends were observed in TNFa and IL-6 protein levels. Following oleic acid (OA) treatment of HepG2 cells, TLR4, TNFa, and IL-6 levels were significantly decreased in the miR-182-5p group as compared with levels observed in controls. Following miR-182-5p administration, TLR4 mRNA and protein levels decreased along with those of TNFa and IL-6 proteins, and the liver weight/body weight ratio of treated mice was less than that observed in controls. Furthermore, hematoxylin and eosin staining showed that the miR-182-5p-treated group exhibited low adiposecell cross-sectional areas, and Oil Red O staining showed decreases in the size of lipid droplets in the miR-182-5p-treated group.

Conclusions: miR-182-5p ameliorated HFD-induced NASH by suppressing TLR4.

Keywords: Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis; Toll-like receptor 4; miR-182-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cells, Cultured
  • Dietary Fats / toxicity
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Regulation
  • Liver / drug effects
  • Liver / pathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / pharmacology*
  • Non-alcoholic Fatty Liver Disease / drug therapy
  • Non-alcoholic Fatty Liver Disease / genetics*
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Oxidative Stress
  • RNA / genetics
  • Toll-Like Receptor 4 / antagonists & inhibitors
  • Toll-Like Receptor 4 / biosynthesis
  • Toll-Like Receptor 4 / genetics

Substances

  • Dietary Fats
  • MicroRNAs
  • Mirn182 microRNA, mouse
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • RNA