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

Kong L, Ren W, Li W, Zhao S, Mi H, Wang R, Zhang Y, Wu W, Nan Y, Yu J - Lipids Health Dis (2011)

Bottom Line: However, the role of PPARα in alcoholic liver disease is largely unknown.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, China.

ABSTRACT

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.

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Related in: MedlinePlus

Effect of PPARα induction by WY14643 on hepatic expression of pro-inflammatory factors. (A1) Expression level of PI3K mRNA and (A2) protein; (B1) Expression level of OPN mRNA and (B2) protein; (C1) Expression level of COX-2 mRNA and (C2) protein in various treatment groups. Data are expressed as the mean ± SD (n = 6 per group). *P < 0.05, **P < 0.01, ***P < 0.001 compared with Control group; #P < 0.05, ##P < 0.01, ###P < 0.001 compared with Ethanol group.
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Figure 5: Effect of PPARα induction by WY14643 on hepatic expression of pro-inflammatory factors. (A1) Expression level of PI3K mRNA and (A2) protein; (B1) Expression level of OPN mRNA and (B2) protein; (C1) Expression level of COX-2 mRNA and (C2) protein in various treatment groups. Data are expressed as the mean ± SD (n = 6 per group). *P < 0.05, **P < 0.01, ***P < 0.001 compared with Control group; #P < 0.05, ##P < 0.01, ###P < 0.001 compared with Ethanol group.

Mentions: We further evaluated the role of PPARα in the development of ethanol induced liver injury by assessing the hepatic expression levels of pro-inflammatory factors phosphatidylinositol 3-kinase (PI3K), OPN and COX-2. We found that ethanol increased the expression of PI3K, OPN and COX-2. Mice treated with WY14643 showed significantly reduced hepatic mRNA and protein expression for PI3K (P < 0.001 and P < 0.01, respectively), OPN (P < 0.001 and P < 0.001) and COX-2 (P < 0.01 and P < 0.05) as compared with mice fed with ethanol liquid diet only (Figure 5). On the other hand, GW6471 further increased PI3K protein (P < 0.05) and COX-2 mRNA (P < 0.05) expression, but didn't affect OPN expression.


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

Kong L, Ren W, Li W, Zhao S, Mi H, Wang R, Zhang Y, Wu W, Nan Y, Yu J - Lipids Health Dis (2011)

Effect of PPARα induction by WY14643 on hepatic expression of pro-inflammatory factors. (A1) Expression level of PI3K mRNA and (A2) protein; (B1) Expression level of OPN mRNA and (B2) protein; (C1) Expression level of COX-2 mRNA and (C2) protein in various treatment groups. Data are expressed as the mean ± SD (n = 6 per group). *P < 0.05, **P < 0.01, ***P < 0.001 compared with Control group; #P < 0.05, ##P < 0.01, ###P < 0.001 compared with Ethanol group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3278384&req=5

Figure 5: Effect of PPARα induction by WY14643 on hepatic expression of pro-inflammatory factors. (A1) Expression level of PI3K mRNA and (A2) protein; (B1) Expression level of OPN mRNA and (B2) protein; (C1) Expression level of COX-2 mRNA and (C2) protein in various treatment groups. Data are expressed as the mean ± SD (n = 6 per group). *P < 0.05, **P < 0.01, ***P < 0.001 compared with Control group; #P < 0.05, ##P < 0.01, ###P < 0.001 compared with Ethanol group.
Mentions: We further evaluated the role of PPARα in the development of ethanol induced liver injury by assessing the hepatic expression levels of pro-inflammatory factors phosphatidylinositol 3-kinase (PI3K), OPN and COX-2. We found that ethanol increased the expression of PI3K, OPN and COX-2. Mice treated with WY14643 showed significantly reduced hepatic mRNA and protein expression for PI3K (P < 0.001 and P < 0.01, respectively), OPN (P < 0.001 and P < 0.001) and COX-2 (P < 0.01 and P < 0.05) as compared with mice fed with ethanol liquid diet only (Figure 5). On the other hand, GW6471 further increased PI3K protein (P < 0.05) and COX-2 mRNA (P < 0.05) expression, but didn't affect OPN expression.

Bottom Line: However, the role of PPARα in alcoholic liver disease is largely unknown.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, China.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus