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

Lipids in Health and Disease

Jun Yu²  Yuemin Nan¹  Wenjuan Wu¹  Yuguo Zhang¹  Rongqi Wang¹  Hongmei Mi¹  Suxian Zhao¹  Wencong Li¹  Weiguang Ren¹  Lingbo Kong¹ 

[1] Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, China;Institute of Digestive Disease and Department of Medicine and Therapeutics, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong

关键词: animal experiment;    steatohepatitis;    ethanol;    Peroxisome proliferator activated receptor alpha;   

Others  :  1212341
DOI  :  10.1186/1476-511X-10-246

 received in 2011-11-19, accepted in 2011-12-30,  发布年份 2011

【 摘 要 】

Background

Peroxisome proliferator activated receptor alpha (PPARα) regulates lipids metabolism and inhibits inflammatory response. However, the role of PPARα in alcoholic liver disease is largely unknown. We aim to elucidate the effect and the molecular basis of PPARα 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 PPARα, 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 PPARα by PPARα agonist WY14643 treatment for 2 weeks ameliorated the severity of liver injury and restored expression of genes altered by ethanol treatment. However, administration of PPARα antagonist GW6471 for 2 weeks promoted the inflammatory response.

Conclusions

The present study provided the evidence for the protective role of PPARα in ameliorating ethanol induced liver injury through modulation of the genes related to lipid metabolism and inflammatory response.

【 授权许可】

   
2011 Kong et al; licensee BioMed Central Ltd.

【 图 表 】

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