Expression of NLRP3 inflammasome and T cell population markers in adipose tissue are associated with insulin resistance and impaired glucose metabolism in humans.
Recent studies in rodents indicate that the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome and a proinflammatory shift in the T cell population in adipose tissue (AT) contribute to AT inflammation and insulin resistance. We investigated: (1) the interplay between the NLRP3 inflammasome and T cell populations in abdominal subcutaneous AT in obese and lean humans in relation to AT inflammatory processes, and (2) involvement of the NLRP3 inflammasome and T cell populations in insulin resistance. Abdominal subcutaneous AT biopsies were collected in 10 obese men with impaired glucose tolerance and 9 lean normal glucose tolerant age-matched controls. AT gene expression of NLRP3 inflammasome-related genes and markers of T cell populations, chemoattraction, macrophage infiltration and other aspects of inflammation were examined. Furthermore, we examined systemic adaptive immune activation and insulin sensitivity (hyperinsulinemic-euglycemic clamp). CASPASE-1 mRNA and the proportion of T(h)1 transcripts (TBX21/CD3ɛ) were significantly higher in AT from obese compared with lean subjects. CASPASE-1 expression and a relative increase in T(h)1 transcripts in AT were strongly associated with insulin resistance and impairments in glucose homeostasis. Gene expression of NLRP3, CASPASE-1, CD3ɛ (pan T cells), TBX21 (T(h)1 cells) and RORC (T(h)17 cells) was positively, whereas GATA3 (T(h)2 cells) was inversely correlated with AT inflammation. Our data suggest that NLRP3 inflammasome activation and a T(h)1 shift in the T cell population in AT of obese subjects is related to insulin resistance and impaired glucose metabolism, which may be explained by AT inflammatory processes.
Department of Human Biology, NUTRIM School for Nutrition, Toxicology & Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands. G.Goossens@maastrichtuniversity.nl
Gijs H
GH
Goossens
Ellen E
EE
Blaak
Ruud
R
Theunissen
Adriaan M
AM
Duijvestijn
Karine
K
Clément
Jan-Willem Cohen
JW
Tervaert
Marielle M
MM
Thewissen
D000273:Adipose Tissue / Q000166:cytology / Q000276:immunology*; D000818:Animals; D002352:Carrier Proteins / Q000276:immunology*; D020170:Caspase 1 / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D058847:Inflammasomes / Q000276:immunology*; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008875:Middle Aged; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D002352:Carrier Proteins; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; C492716:Nlrp3 protein, mouse; D020170:Caspase 1; D005947:Glucose