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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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Effects of ethanol with treatment of WY14643 or GW6471 on serum (A) ALT level and (B) AST level. Data are expressed as the mean ± SD (n = 6 per group). ***P < 0.001 compared with Control group; ##P < 0.01, ###P < 0.001 compared with Ethanol group.
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Figure 1: Effects of ethanol with treatment of WY14643 or GW6471 on serum (A) ALT level and (B) AST level. Data are expressed as the mean ± SD (n = 6 per group). ***P < 0.001 compared with Control group; ##P < 0.01, ###P < 0.001 compared with Ethanol group.

Mentions: As shown in Figure 1, mice fed with 4% ethanol-containing Lieber-DeCarli liquid diet for 12 weeks showed significantly higher serum ALT and AST levels (P < 0.001) compared with Control group, indicating hepatic injury. A significant reduction of serum ALT and AST levels (P < 0.001) was noticed after WY14643 treatment. However, GW6471 treatment further elevated the ALT level (P < 0.01) than those fed ethanol liquid diet only (Figure 1).


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)

Effects of ethanol with treatment of WY14643 or GW6471 on serum (A) ALT level and (B) AST level. Data are expressed as the mean ± SD (n = 6 per group). ***P < 0.001 compared with Control group; ##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 1: Effects of ethanol with treatment of WY14643 or GW6471 on serum (A) ALT level and (B) AST level. Data are expressed as the mean ± SD (n = 6 per group). ***P < 0.001 compared with Control group; ##P < 0.01, ###P < 0.001 compared with Ethanol group.
Mentions: As shown in Figure 1, mice fed with 4% ethanol-containing Lieber-DeCarli liquid diet for 12 weeks showed significantly higher serum ALT and AST levels (P < 0.001) compared with Control group, indicating hepatic injury. A significant reduction of serum ALT and AST levels (P < 0.001) was noticed after WY14643 treatment. However, GW6471 treatment further elevated the ALT level (P < 0.01) than those fed ethanol liquid diet only (Figure 1).

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