Pioglitazone prevents hepatic steatosis, fibrosis, and enzyme-altered lesions in rat liver cirrhosis induced by a choline-deficient L-amino acid-defined diet

Biochem Biophys Res Commun. 2004 Feb 27;315(1):187-95. doi: 10.1016/j.bbrc.2004.01.038.


Non-alcoholic steatohepatitis (NASH) may progress to liver cirrhosis, and NASH patients with liver cirrhosis have a risk of development of hepatocellular carcinoma. Peroxisome proliferator-activated receptor (PPAR) gamma ligand has recently been reported to have improved the condition of patients with NASH. The aim of this study was to investigate whether pioglitazone, a PPARgamma ligand, has any influence on the animal model of NASH as well as isolated hepatic stellate cells. In vivo, the effects of pioglitazone were examined using the choline-deficient L-amino acid-defined (CDAA)-diet liver fibrosis model. After two weeks, pioglitazone improved hepatic steatosis, prevented liver fibrosis, and reduced preneoplastic lesions in the liver after 10 weeks. Pioglitazone reduced the expression of TIMP-1 and TIMP-2 mRNA without changing MMP-13 mRNA expression compared to the liver fed a CDAA diet alone. In vitro, pioglitazone prevented the activation of hepatic stellate cells resulting in reducing the expression of type I procollagen, MMP-2, TIMP-1, and TIMP-2 mRNA with increased MMP-13 mRNA expression. These results indicate that pioglitazone may be one of the candidates for the benefit drugs for the liver disease of patients with NASH.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids
  • Animal Feed
  • Animals
  • Biomarkers / blood
  • Body Weight
  • Choline Deficiency / complications*
  • Fatty Liver / etiology
  • Fatty Liver / metabolism
  • Fatty Liver / prevention & control*
  • Fibrosis
  • Glutathione Transferase / biosynthesis
  • Immunohistochemistry
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology*
  • Liver Cirrhosis, Experimental / metabolism*
  • Liver Cirrhosis, Experimental / pathology
  • Liver Cirrhosis, Experimental / prevention & control*
  • Male
  • Matrix Metalloproteinases / metabolism
  • Muscle, Smooth / metabolism
  • Organ Size
  • Pioglitazone
  • Procollagen / metabolism
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Wistar
  • Thiazolidinediones / pharmacology*
  • Tissue Inhibitor of Metalloproteinases / metabolism
  • Triglycerides / metabolism


  • Amino Acids
  • Biomarkers
  • Procollagen
  • RNA, Messenger
  • Thiazolidinediones
  • Tissue Inhibitor of Metalloproteinases
  • Triglycerides
  • Glutathione Transferase
  • Matrix Metalloproteinases
  • Pioglitazone