1. Peroxisome proliferator-activated receptor-delta agonist ameliorated inflammasome activation in nonalcoholic fatty liver disease.
- Author
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Lee HJ, Yeon JE, Ko EJ, Yoon EL, Suh SJ, Kang K, Kim HR, Kang SH, Yoo YJ, Je J, Lee BJ, Kim JH, Seo YS, Yim HJ, and Byun KS
- Subjects
- Animals, Blood Glucose drug effects, Blood Glucose metabolism, Cytoprotection, Diet, High-Fat, Disease Models, Animal, Gene Expression Regulation, Hep G2 Cells, Hepatocytes drug effects, Hepatocytes metabolism, Hepatocytes pathology, Humans, Inflammasomes genetics, Inflammasomes metabolism, Inflammation Mediators metabolism, Lipopolysaccharides, Liver metabolism, Liver pathology, Male, Mice, Inbred C57BL, Non-alcoholic Fatty Liver Disease genetics, Non-alcoholic Fatty Liver Disease metabolism, Non-alcoholic Fatty Liver Disease pathology, Oxidative Stress drug effects, PPAR delta metabolism, Palmitic Acid toxicity, Signal Transduction drug effects, Time Factors, Anti-Inflammatory Agents pharmacology, Inflammasomes antagonists & inhibitors, Liver drug effects, Non-alcoholic Fatty Liver Disease prevention & control, PPAR delta agonists, Thiazoles pharmacology
- Abstract
Aim: To evaluate the inflammasome activation and the effect of peroxisome proliferator-activated receptors (PPAR)-δ agonist treatment in nonalcoholic fatty liver disease (NAFLD) models., Methods: Male C57BL/6J mice were classified according to control or high fat diet (HFD) with or without PPAR-δ agonist (GW) over period of 12 wk [control, HFD, HFD + lipopolysaccharide (LPS), HFD + LPS + GW group]. HepG2 cells were exposed to palmitic acid (PA) and/or LPS in the absence or presence of GW., Results: HFD caused glucose intolerance and hepatic steatosis. In mice fed an HFD with LPS, caspase-1 and interleukin (IL)-1β in the liver were significantly increased. Treatment with GW ameliorated the steatosis and inhibited overexpression of pro-inflammatory cytokines. In HepG2 cells, PA and LPS treatment markedly increased mRNA of several nucleotide-binding and oligomerization domain-like receptor family members (NLRP3, NLRP6, and NLRP10), caspase-1 and IL-1β. PA and LPS also exaggerated reactive oxygen species production. All of the above effects of PA and LPS were reduced by GW. GW also enhanced the phosphorylation of AMPK-α., Conclusion: PPAR-δ agonist reduces fatty acid-induced inflammation and steatosis by suppressing inflammasome activation. Targeting the inflammasome by the PPAR-δ agonist may have therapeutic implication for NAFLD.
- Published
- 2015
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