Peroxisome proliferator-activated receptor-delta agonist ameliorated inflammasome activation in nonalcoholic fatty liver disease

被引：76

作者：

Lee, Hyun Jung ^{[1
]}

Yeon, Jong Eun ^{[1
]}

Ko, Eun Jung ^{[1
]}

Yoon, Eileen L. ^{[1
]}

Suh, Sang Jun ^{[1
]}

Kang, Keunhee ^{[1
]}

Kim, Hae Rim ^{[1
]}

Kang, Seoung Hee ^{[1
]}

Yoo, Yang Jae ^{[1
]}

Je, Jihye ^{[1
]}

Lee, Beom Jae ^{[1
]}

Kim, Ji Hoon ^{[1
]}

Seo, Yeon Seok ^{[1
]}

Yim, Hyung Joon ^{[1
]}

Byun, Kwan Soo ^{[1
]}

机构：

[1] Korea Univ, Coll Med, Dept Internal Med, Seoul 152703, South Korea

来源：

WORLD JOURNAL OF GASTROENTEROLOGY | 2015年 / 21卷 / 45期

关键词：

Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; Inflammasome; Nucleotide-binding and oligomerization domain-like receptor; Peroxisome proliferator-activated receptors delta; NLRP3; INFLAMMASOME; INSULIN SENSITIVITY; OVERWEIGHT PATIENTS; GLUCOSE-METABOLISM; MEDITERRANEAN DIET; STEATOHEPATITIS; ACID; OBESITY; EXPRESSION; MICE;

D O I：

10.3748/wjg.v21.i45.12787

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

100201 [内科学];

摘要：

AIM: To evaluate the inflammasome activation and the effect of peroxisome proliferator-activated receptors (PPAR)-delta 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-delta 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)-1 beta 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-1 beta. 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-alpha. CONCLUSION: PPAR-delta agonist reduces fatty acid-induced inflammation and steatosis by suppressing inflammasome activation. Targeting the inflammasome by the PPAR-delta agonist may have therapeutic implication for NAFLD. Key words: Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; Inflammasome; Nucleotide-binding and oligomerization domain-like receptor; Peroxisome proliferator-activated receptors delta

引用

页码：12787 / 12799

页数：13

共 41 条

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