Endoplasmic reticulum stress involved in the course of lipogenesis in fatty acids-induced hepatic steatosis

J Gastroenterol Hepatol. 2010 Mar;25(3):613-8. doi: 10.1111/j.1440-1746.2009.06086.x. Epub 2009 Nov 19.

Abstract

Background and aims: The aim of the present study is to elucidate whether endoplasmic reticulum stress involved in the course of lipogenesis in fatty acids induced hepatic steatosis and the potential effect of metformin on endoplasmic reticulum stress.

Methods: HepG2 cells were exposed to different types of culture media. After incubation for 24 h, cells were harvested to evaluate cell survival rate and lipid level among different groups. Moreover, reverse transcriptase polymerase chain reaction and western blot for glucose-regulated protein-78 (GRP78), sterol response element-binding protein-1c (SREBP1c) and fatty acid synthase (FAS) were applied.

Results: The levels of triglyceride (TG), mRNA of FAS, mRNA and protein of GRP78 and SREBP1c significantly increased in the free fatty acids (FFA)-induced hepatic steatosis group. Then, HepG2 cells with hepatic steatosis induced by FFA were treated by metformin, levels of TG, GRP78 mRNA, SREBP1c mRNA and FAS mRNA as well as GRP78 and SREBP1 protein levels were partially decreased but without significant differences.

Conclusion: Endoplasmic reticulum stress might be involved in lipogenesis in fatty acids-induced hepatic steatosis. Therefore, endoplasmic reticulum stress might serve as a novel target in the pathogenesis and therapy of non-alcoholic fatty liver disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Survival
  • Endoplasmic Reticulum / drug effects
  • Endoplasmic Reticulum / metabolism*
  • Endoplasmic Reticulum Chaperone BiP
  • Fatty Acids / metabolism*
  • Fatty Acids, Nonesterified / metabolism
  • Fatty Liver / drug therapy
  • Fatty Liver / etiology
  • Fatty Liver / metabolism*
  • Fatty Liver / pathology
  • HSP70 Heat-Shock Proteins / metabolism
  • Heat-Shock Proteins / metabolism
  • Hep G2 Cells
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • In Vitro Techniques
  • Lipogenesis* / drug effects
  • Membrane Proteins / metabolism
  • Metformin / pharmacology
  • Metformin / therapeutic use
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sterol Regulatory Element Binding Protein 1 / metabolism
  • Triglycerides / metabolism

Substances

  • Endoplasmic Reticulum Chaperone BiP
  • Fatty Acids
  • Fatty Acids, Nonesterified
  • HSP70 Heat-Shock Proteins
  • HSPA5 protein, human
  • Heat-Shock Proteins
  • Hypoglycemic Agents
  • Membrane Proteins
  • RNA, Messenger
  • Sterol Regulatory Element Binding Protein 1
  • Triglycerides
  • glucose-regulated proteins
  • Metformin