Background: Steatosis in chronic hepatitis C is associated with inflammation and accelerated fibrogenesis. Aim: To assess the contribution of peroxisome proliferator-activated receptor-α and -γ to the pathogenesis of hepatitis C virus associated steatosis is unknown. Methods: We measured peroxisome proliferator-activated receptor (PPAR)-α and -γ mRNA by quantitative polymerase chain reaction in liver biopsies of 35 genotype 1 and 22 genotype 3 infected patients and in Huh7 cells expressing hepatitis C virus 1b or 3a core protein. Results: PPAR-α mRNA was significantly reduced in livers of patients with genotype 3 compared with genotype 1. Steatosis was associated to a decreased expression of PPAR-α in genotype 1, but not in genotype 3. PPAR-γ expression was significantly lower in genotype 3 compared with genotype 1 and steatosis was associated to decreased levels of PPAR-γ, but only in genotype 1. There was no significant relationship between PPARs mRNA levels and liver activity or fibrosis. Expression of the hepatitis C virus 3a core protein was associated with an increase in triglyceride accumulation and with a significant reduction of PPAR-γ mRNA compared with hepatitis C virus 1b. Conclusions: The presence of steatosis and hepatitis C virus genotype 3 are both associated with a significant down-regulation of PPARs. These receptors, and also additional factors, seem to play a role in the pathogenesis of hepatitis C virus-associated steatosis.
ASJC Scopus subject areas
- Pharmacology (medical)
- Pharmacology, Toxicology and Pharmaceutics(all)