title: Lower NLRP3 inflammasome activity in NAG-1 transgenic mice is linked to a resistance to obesity and increased insulin sensitivity.
abstract: OBJECTIVE
  The NLRP3 inflammasome plays an important regulatory role in obesity-induced insulin resistance. NSAID activated gene-1 (NAG-1) is a divergent member of the TGF-β superfamily. NAG-1 Tg mice are resistant to dietary- and genetic-induced obesity and have improved insulin sensitivity. The objective was to examine whether NLRP3 inflammasome activity is associated with this observed phenotype in NAG-1 Tg mice.
  
  
  METHODS
  Key components of the NLRP3 inflammasome were examined in NAG-1 Tg mice on both regular and high fat diet (HFD) conditions.
  
  
  RESULTS
  The expression of caspase-1 and ASC, key components of the NLRP3 inflammasome, is significantly reduced at mRNA and protein levels in white adipose tissue (WAT) of NAG-1 Tg mice. HFD increases the expression of caspase-1 and ASC in WT mice, but their expression is reduced in NAG-1 Tg mice. Furthermore, there is reduced IL-18, IL-1β, and TNF-α expression in the WAT of NAG-1 Tg mice. NAG-1 Tg mice have significantly lower serum leptin and insulin levels and reduced expression of macrophage infiltration markers (F4/80, CD11b, and CD11c) in WAT.
  
  
  CONCLUSIONS
  The study suggests the lower NLRP3 inflammasome activity may play a role in the resistance of NAG-1 Tg mice to diet-induced obesity and improved insulin sensitivity.
authors.affiliation: Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences (NIEHS), 111. T.W. Alexander Dr, Research Triangle Park, North Carolina, USA.
authors.forename: Xingya
authors.initials: X
authors.lastname: Wang
authors.forename: Kali
authors.initials: K
authors.lastname: Chrysovergis
authors.forename: Justin
authors.initials: J
authors.lastname: Kosak
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Eling
mesh_terms: D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D039481:CD11b Antigen / Q000235:genetics / Q000378:metabolism; D039521:CD11c Antigen / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D020170:Caspase 1 / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat; D005260:Female; D058847:Inflammasomes / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics*; D020382:Interleukin-18 / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D020738:Leptin / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D039481:CD11b Antigen; D039521:CD11c Antigen; D002352:Carrier Proteins; D058847:Inflammasomes; D007328:Insulin; D020382:Interleukin-18; D053583:Interleukin-1beta; D020738:Leptin; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D020170:Caspase 1