title: Peroxisome proliferator-activated receptor-delta agonist ameliorated inflammasome activation in nonalcoholic fatty liver disease.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Hyun Jung Lee, Jong Eun Yeon, Eun Jung Ko, Eileen L Yoon, Sang Jun Suh, Keunhee Kang, Hae Rim Kim, Seoung Hee Kang, Yang Jae Yoo, Jihye Je, Beom Jae Lee, Ji Hoon Kim, Yeon Seok Seo, Hyung Joon Yim, Kwan Soo Byun, Department of Internal Medicine, Korea University College of Medicine, Seoul 152-703, South Korea.
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Hyun Jung Lee, Jong Eun Yeon, Eun Jung Ko, Eileen L Yoon, Sang Jun Suh, Keunhee Kang, Hae Rim Kim, Seoung Hee Kang, Yang Jae Yoo, Jihye Je, Beom Jae Lee, Ji Hoon Kim, Yeon Seok Seo, Hyung Joon Yim, Kwan Soo Byun, Department of Internal Medicine, Korea University College of Medicine, Seoul 152-703, South Korea.
authors.forename: Jong Eun
authors.initials: JE
authors.lastname: Yeon
authors.affiliation: Hyun Jung Lee, Jong Eun Yeon, Eun Jung Ko, Eileen L Yoon, Sang Jun Suh, Keunhee Kang, Hae Rim Kim, Seoung Hee Kang, Yang Jae Yoo, Jihye Je, Beom Jae Lee, Ji Hoon Kim, Yeon Seok Seo, Hyung Joon Yim, Kwan Soo Byun, Department of Internal Medicine, Korea University College of Medicine, Seoul 152-703, South Korea.
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Ko
authors.affiliation: Hyun Jung Lee, Jong Eun Yeon, Eun Jung Ko, Eileen L Yoon, Sang Jun Suh, Keunhee Kang, Hae Rim Kim, Seoung Hee Kang, Yang Jae Yoo, Jihye Je, Beom Jae Lee, Ji Hoon Kim, Yeon Seok Seo, Hyung Joon Yim, Kwan Soo Byun, Department of Internal Medicine, Korea University College of Medicine, Seoul 152-703, South Korea.
authors.forename: Eileen L
authors.initials: EL
authors.lastname: Yoon
authors.affiliation: Hyun Jung Lee, Jong Eun Yeon, Eun Jung Ko, Eileen L Yoon, Sang Jun Suh, Keunhee Kang, Hae Rim Kim, Seoung Hee Kang, Yang Jae Yoo, Jihye Je, Beom Jae Lee, Ji Hoon Kim, Yeon Seok Seo, Hyung Joon Yim, Kwan Soo Byun, Department of Internal Medicine, Korea University College of Medicine, Seoul 152-703, South Korea.
authors.forename: Sang Jun
authors.initials: SJ
authors.lastname: Suh
authors.affiliation: Hyun Jung Lee, Jong Eun Yeon, Eun Jung Ko, Eileen L Yoon, Sang Jun Suh, Keunhee Kang, Hae Rim Kim, Seoung Hee Kang, Yang Jae Yoo, Jihye Je, Beom Jae Lee, Ji Hoon Kim, Yeon Seok Seo, Hyung Joon Yim, Kwan Soo Byun, Department of Internal Medicine, Korea University College of Medicine, Seoul 152-703, South Korea.
authors.forename: Keunhee
authors.initials: K
authors.lastname: Kang
authors.affiliation: Hyun Jung Lee, Jong Eun Yeon, Eun Jung Ko, Eileen L Yoon, Sang Jun Suh, Keunhee Kang, Hae Rim Kim, Seoung Hee Kang, Yang Jae Yoo, Jihye Je, Beom Jae Lee, Ji Hoon Kim, Yeon Seok Seo, Hyung Joon Yim, Kwan Soo Byun, Department of Internal Medicine, Korea University College of Medicine, Seoul 152-703, South Korea.
authors.forename: Hae Rim
authors.initials: HR
authors.lastname: Kim
authors.affiliation: Hyun Jung Lee, Jong Eun Yeon, Eun Jung Ko, Eileen L Yoon, Sang Jun Suh, Keunhee Kang, Hae Rim Kim, Seoung Hee Kang, Yang Jae Yoo, Jihye Je, Beom Jae Lee, Ji Hoon Kim, Yeon Seok Seo, Hyung Joon Yim, Kwan Soo Byun, Department of Internal Medicine, Korea University College of Medicine, Seoul 152-703, South Korea.
authors.forename: Seoung Hee
authors.initials: SH
authors.lastname: Kang
authors.affiliation: Hyun Jung Lee, Jong Eun Yeon, Eun Jung Ko, Eileen L Yoon, Sang Jun Suh, Keunhee Kang, Hae Rim Kim, Seoung Hee Kang, Yang Jae Yoo, Jihye Je, Beom Jae Lee, Ji Hoon Kim, Yeon Seok Seo, Hyung Joon Yim, Kwan Soo Byun, Department of Internal Medicine, Korea University College of Medicine, Seoul 152-703, South Korea.
authors.forename: Yang Jae
authors.initials: YJ
authors.lastname: Yoo
authors.affiliation: Hyun Jung Lee, Jong Eun Yeon, Eun Jung Ko, Eileen L Yoon, Sang Jun Suh, Keunhee Kang, Hae Rim Kim, Seoung Hee Kang, Yang Jae Yoo, Jihye Je, Beom Jae Lee, Ji Hoon Kim, Yeon Seok Seo, Hyung Joon Yim, Kwan Soo Byun, Department of Internal Medicine, Korea University College of Medicine, Seoul 152-703, South Korea.
authors.forename: Jihye
authors.initials: J
authors.lastname: Je
authors.affiliation: Hyun Jung Lee, Jong Eun Yeon, Eun Jung Ko, Eileen L Yoon, Sang Jun Suh, Keunhee Kang, Hae Rim Kim, Seoung Hee Kang, Yang Jae Yoo, Jihye Je, Beom Jae Lee, Ji Hoon Kim, Yeon Seok Seo, Hyung Joon Yim, Kwan Soo Byun, Department of Internal Medicine, Korea University College of Medicine, Seoul 152-703, South Korea.
authors.forename: Beom Jae
authors.initials: BJ
authors.lastname: Lee
authors.affiliation: Hyun Jung Lee, Jong Eun Yeon, Eun Jung Ko, Eileen L Yoon, Sang Jun Suh, Keunhee Kang, Hae Rim Kim, Seoung Hee Kang, Yang Jae Yoo, Jihye Je, Beom Jae Lee, Ji Hoon Kim, Yeon Seok Seo, Hyung Joon Yim, Kwan Soo Byun, Department of Internal Medicine, Korea University College of Medicine, Seoul 152-703, South Korea.
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Hyun Jung Lee, Jong Eun Yeon, Eun Jung Ko, Eileen L Yoon, Sang Jun Suh, Keunhee Kang, Hae Rim Kim, Seoung Hee Kang, Yang Jae Yoo, Jihye Je, Beom Jae Lee, Ji Hoon Kim, Yeon Seok Seo, Hyung Joon Yim, Kwan Soo Byun, Department of Internal Medicine, Korea University College of Medicine, Seoul 152-703, South Korea.
authors.forename: Yeon Seok
authors.initials: YS
authors.lastname: Seo
authors.affiliation: Hyun Jung Lee, Jong Eun Yeon, Eun Jung Ko, Eileen L Yoon, Sang Jun Suh, Keunhee Kang, Hae Rim Kim, Seoung Hee Kang, Yang Jae Yoo, Jihye Je, Beom Jae Lee, Ji Hoon Kim, Yeon Seok Seo, Hyung Joon Yim, Kwan Soo Byun, Department of Internal Medicine, Korea University College of Medicine, Seoul 152-703, South Korea.
authors.forename: Hyung Joon
authors.initials: HJ
authors.lastname: Yim
authors.affiliation: Hyun Jung Lee, Jong Eun Yeon, Eun Jung Ko, Eileen L Yoon, Sang Jun Suh, Keunhee Kang, Hae Rim Kim, Seoung Hee Kang, Yang Jae Yoo, Jihye Je, Beom Jae Lee, Ji Hoon Kim, Yeon Seok Seo, Hyung Joon Yim, Kwan Soo Byun, Department of Internal Medicine, Korea University College of Medicine, Seoul 152-703, South Korea.
authors.forename: Kwan Soo
authors.initials: KS
authors.lastname: Byun
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D019610:Cytoprotection; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D058847:Inflammasomes / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D018384:Oxidative Stress / Q000187:drug effects; D047494:PPAR delta / Q000819:agonists* / Q000378:metabolism; D019308:Palmitic Acid / Q000633:toxicity; D015398:Signal Transduction / Q000187:drug effects; D013844:Thiazoles / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D001786:Blood Glucose; C425931:GW 501516; D058847:Inflammasomes; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D047494:PPAR delta; D013844:Thiazoles; C440499:lipopolysaccharide, Escherichia coli O111 B4; D019308:Palmitic Acid
keywords: Inflammasome; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; Nucleotide-binding and oligomerization domain-like receptor; Peroxisome proliferator-activated receptors delta