title: Obesity phenotype is related to NLRP3 inflammasome activity and immunological profile of visceral adipose tissue.
abstract: OBJECTIVE
  Obesity is a heterogeneous condition comprising both individuals who remain metabolically healthy (MHO) and those who develop metabolic disorders (metabolically unhealthy, MUO). Adipose tissue is also heterogeneous in that its visceral component is more frequently associated with metabolic dysfunction than its subcutaneous component. The development of metabolic disorders is partly mediated by the NLR family pyrin domain containing-3 (NLRP3) inflammasome, which increases the secretion of inflammatory cytokines via activation of caspase-1. We compared the immunological profile and NLRP3 activity in adipose tissue between MUO and MHO individuals.
  
  
  METHODS
  MHO and MUO phenotypes were defined, respectively, as the absence and the presence of the metabolic syndrome. Cellular composition and intrinsic inflammasome activity were investigated by flow cytometry, quantitative RT-PCR and tissue culture studies in subcutaneous and visceral adipose tissue from 23 MUO, 21 MHO and nine lean individuals.
  
  
  RESULTS
  We found significant differences between the three study groups, including an increased secretion of IL-1β, increased expression of IL1B and NLRP3, increased number of adipose tissue macrophages and decreased number of regulatory T cells in the visceral adipose tissue of MUO patients compared with MHO and lean participants. In macrophages derived from visceral adipose tissue, both caspase-1 activity and IL-1β levels were higher in MUO patients than in MHO patients. Furthermore, caspase-1 activity was higher in CD11c(+)CD206(+) adipose tissue macrophages than in CD11c(-)CD206(+) cells.
  
  
  CONCLUSIONS
  The MUO phenotype seems to be associated with an increased activation of the NLPR3 inflammasome in macrophages infiltrating visceral adipose tissue, and a less favourable inflammatory profile compared with the MHO phenotype.
authors.affiliation: Virology and Immunology Unit, GIGA-ST, University of Liege, Liege, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Esser
authors.forename: Laurent
authors.initials: L
authors.lastname: L'homme
authors.forename: Arnaud
authors.initials: A
authors.lastname: De Roover
authors.forename: Laurent
authors.initials: L
authors.lastname: Kohnen
authors.forename: André J
authors.initials: AJ
authors.lastname: Scheen
authors.forename: Michel
authors.initials: M
authors.lastname: Moutschen
authors.forename: Jacques
authors.initials: J
authors.lastname: Piette
authors.forename: Sylvie
authors.initials: S
authors.lastname: Legrand-Poels
authors.forename: Nicolas
authors.initials: N
authors.lastname: Paquot
mesh_terms: D000328:Adult; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D020382:Interleukin-18 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D050152:Intra-Abdominal Fat / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009765:Obesity / Q000276:immunology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human