Activation of peroxisome proliferator activated receptor alpha ameliorates ethanol induced steatohepatitis in mice

Abstract

Background: Peroxisome proliferator activated receptor alpha (PPAR) regulates lipids metabolism and inhibits inflammatory response. However, the role of PPAR in alcoholic liver disease is largely unknown. We aim to elucidate the effect and the molecular basis of PPAR in ethanol induced hepatic injury in mice. Results: C57BL/6J mice fed with 4% ethanol-containing Lieber-DeCarli liquid diet for 12 weeks exhibited hepatocyte steatosis, necrosis and inflammatory infiltration, accompanied with elevated serum alanine aminotransferase (ALT) and aspartic transaminase (AST) levels, decreased hepatic expression of PPAR, lipids oxidation promoting genes and anti-inflammatory factors, as well as enhanced hepatic expression of fatty acids synthesis promoting genes and pro-inflammatory cytokines. Induction of PPAR by PPAR agonist WY14643 treatment for 2 weeks ameliorated the severity of liver injury and restored expression of genes altered by ethanol treatment. However, administration of PPAR antagonist GW6471 for 2 weeks promoted the inflammatory response. Conclusions: The present study provided the evidence for the protective role of PPAR in ameliorating ethanol induced liver injury through modulation of the genes related to lipid metabolism and inflammatory response. © 2011 Kong et al; licensee BioMed Central Ltd.