[en] Aims/hypothesis 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 RTPCR
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/interpretation 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.
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