摘要
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]. Hep G2 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 Hep G2 cells, PA and LPS treatment markedly increased m RNA of several nucleotide-binding andoligomerization 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 acidinduced inflammation and steatosis by suppressing inflammasome activation. Targeting the inflammasome by the PPAR-δ agonist may have therapeutic implication for NAFLD.
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]. Hep G2 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 Hep G2 cells, PA and LPS treatment markedly increased m RNA of several nucleotide-binding andoligomerization 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 acidinduced inflammation and steatosis by suppressing inflammasome activation. Targeting the inflammasome by the PPAR-δ agonist may have therapeutic implication for NAFLD.
