Activation of peroxisome proliferator activated receptor alpha ameliorates ethanol induced steatohepatitis in mice.
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.
Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, China.
Lingbo
L
Kong
Weiguang
W
Ren
Wencong
W
Li
Suxian
S
Zhao
Hongmei
H
Mi
Rongqi
R
Wang
Yuguo
Y
Zhang
Wenjuan
W
Wu
Yuemin
Y
Nan
Jun
J
Yu
D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D000431:Ethanol; D005235:Fatty Liver, Alcoholic / Q000097:blood / Q000378:metabolism / Q000517:prevention & control*; D015870:Gene Expression / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D050356:Lipid Metabolism / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D047493:PPAR alpha / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use
D052242:Adiponectin; D018836:Inflammation Mediators; D047493:PPAR alpha; D011743:Pyrimidines; D000431:Ethanol; C006253:pirinixic acid; D051547:Heme Oxygenase-1; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase