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

Abstract

BackgroundPeroxisome 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.ResultsC57BL/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.ConclusionsThe 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.

Hypoxia-inducible Lipid Droplet-associated (HILPDA) Is a Novel Peroxisome Proliferator-activated Receptor (PPAR) Target Involved in Hepatic Triglyceride Secretion

“…By contrast, administration of synthetic PPAR␣ agonists to rodents decreases fatty liver (45)(46)(47)(48)(49)(50). This apparent discrepancy can be reconciled by the notion that Hilpda is one of more than 100 genes involved in lipid metabolism that are induced by PPAR␣.…”

Activation of peroxisome proliferator activated receptor alpha ameliorates ethanol mediated liver fibrosis in mice

“…Eight-week-old male C57BL/6J mice were bred and housed as previously described [5]. The mice were randomly divided into 4 groups (6 mice per group): control group, mice fed with non-alcoholic control liquid diet (TROPHIC Animal Feed High-tech Co., Ltd., Nantong, China); ethanol group, mice fed with 4% ethanol-containing Lieber-DeCarli liquid diet (TROPHIC); ethanol plus CCl 4 (ethanol+CCl 4 ) group, mice fed with ethanol liquid diet, and received 5% CCl 4 (Sinopharm Chemical Reagent Co., Ltd, Shanghai, China) dissolved in olive oil (Sinopharm) intraperitoneal injection, 2 ml/kg body weight, twice a week; ethanol plus CCl 4 and WY14643 (ethanol+CCl 4 +WY) group, mice fed with ethanol liquid diet with WY14643 (50 mg/kg/d, Cayman Chemical, Ann Arbor, MI, CA), and administrated with 5% CCl 4 intraperitoneal injection (Figure 7).…”

“…Previously, we demonstrated the role of nuclear transcription factor peroxisome proliferators activated receptor alpha (PPARα) in lipid homeostasis and modulation of inflammatory responses in alcoholic steatohepatitis [5]. Induction of PPARα significantly ameliorated the severity of ethanol induced liver injury by regulating expression of lipid metabolism and inflammation related genes.…”

PPARα, PPARγ and SREBP-1 pathways mediated waterborne iron (Fe)-induced reduction in hepatic lipid deposition of javelin goby Synechogobius hasta

“…This suggested that lipid metabolism in hepatocytes of S. hasta was modulated by Fe through the PPARα signaling pathway. Similarly, Kong et al (2011) found that the mRNA level and protein expression of FAS were enhanced by treatment of GW6471 in mice.…”