Therapeutic effects of granulocyte-colony stimulating factor on non-alcoholic hepatic steatosis in the rat

Ann Hepatol. 2013 Jan-Feb;12(1):115-22.

Abstract

Background and rationale: Non-alcoholic hepatic steatosis refers to the accumulation of triglycerides in the liver in the absence of alcohol consumption. Granulocyte colony-stimulating factor (G-CSF) has been reported to be an effective treatment for a variety of liver diseases. We examined the possible therapeutic effects of G-CSF on non-alcoholic hepatic steatosis in rats.

Material and methods: Thirty-week-old Otsuka Long Evans Tokushima Fatty (OLETF) rats received water containing 30% sucrose for 8 weeks to promote the development of non-alcoholic hepatic steatosis. After development of the model, the rats were injected with G-CSF (100 μg/kg/day) or saline for 5 days. Four weeks after this treatment, serum levels of glucose, total cholesterol (TC), triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and free fatty acids (FFA) were measured. Histology was examined by hematoxylin and eosin (H-E) and periodic acid Schiff (PAS) staining, and levels of expression of hepatic lipogenic enzymes were determined by RT-PCR.

Results: The G-CSF-treated rats displayed significantly fewer lipid droplets than the saline-treated rats (P < 0.01), and their levels of sterol regulatory element-binding protein (SREBP)-1c, fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) mRNAs were also lower (P < 0.01), as were their liver weight and serum levels of TG and FFA (P < 0.05).

Conclusion: Our results indicate that G-CSF ameliorated non-alcoholic hepatic steatosis in the OLETF rat, and this therapeutic effect involved a reduction of SREBP-1c expression. Therefore, G-CSF deserves further study as a potential treatment for non-alcoholic hepatic steatosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyl-CoA Carboxylase / genetics
  • Acetyl-CoA Carboxylase / metabolism
  • Alanine Transaminase / blood
  • Animals
  • Aspartate Aminotransferases / blood
  • Blood Glucose / drug effects
  • Cholesterol / blood
  • Fatty Acid Synthases / genetics
  • Fatty Acid Synthases / metabolism
  • Fatty Acids, Nonesterified / blood
  • Fatty Liver / blood
  • Fatty Liver / drug therapy*
  • Fatty Liver / pathology
  • Granulocyte Colony-Stimulating Factor / therapeutic use*
  • Lipogenesis / drug effects
  • Lipogenesis / genetics
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Non-alcoholic Fatty Liver Disease
  • Organ Size / drug effects
  • RNA, Messenger / analysis
  • Rats
  • Rats, Inbred OLETF
  • Real-Time Polymerase Chain Reaction
  • Sterol Regulatory Element Binding Protein 1 / genetics
  • Sterol Regulatory Element Binding Protein 1 / metabolism
  • Triglycerides / blood

Substances

  • Blood Glucose
  • Fatty Acids, Nonesterified
  • RNA, Messenger
  • Srebf1 protein, rat
  • Sterol Regulatory Element Binding Protein 1
  • Triglycerides
  • Granulocyte Colony-Stimulating Factor
  • Cholesterol
  • Fatty Acid Synthases
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Acetyl-CoA Carboxylase