title: T-cell profile in adipose tissue is associated with insulin resistance and systemic inflammation in humans.
abstract: OBJECTIVE
  The biological mechanisms linking obesity to insulin resistance have not been fully elucidated. We have shown that insulin resistance or glucose intolerance in diet-induced obese mice is related to a shift in the ratio of pro- and anti-inflammatory T cells in adipose tissue. We sought to test the hypothesis that the balance of T-cell phenotypes would be similarly related to insulin resistance in human obesity.
  
  
  RESULTS
  Healthy overweight or obese human subjects underwent adipose-tissue biopsies and quantification of insulin-mediated glucose disposal by the modified insulin suppression test. T-cell subsets were quantified by flow cytometry in visceral (VAT) and subcutaneous adipose tissue (SAT). Results showed that CD4 and CD8 T cells infiltrate both depots, with proinflammatory T-helper (Th)-1, Th17, and CD8 T cells, significantly more frequent in VAT as compared with SAT. T-cell profiles in SAT and VAT correlated significantly with one another and with peripheral blood. Th1 frequency in SAT and VAT correlated directly, whereas Th2 frequency in VAT correlated inversely, with plasma high-sensitivity C-reactive protein concentrations. Th2 in both depots and peripheral blood was inversely associated with systemic insulin resistance. Furthermore, Th1 in SAT correlated with plasma interleukin-6. Relative expression of associated cytokines, measured by real-time polymerase chain reaction, reflected flow cytometry results. Most notably, adipose tissue expression of anti-inflammatory interleukin-10 was inversely associated with insulin resistance.
  
  
  CONCLUSIONS
  CD4 and CD8 T cells populate human adipose tissue and the relative frequency of Th1 and Th2 are highly associated with systemic inflammation and insulin resistance. These findings point to the adaptive immune system as a potential mediator between obesity and insulin resistance or inflammation. Identification of antigenic stimuli in adipose tissue may yield novel targets for treatment of obesity-associated metabolic disease.
authors.affiliation: From the Departments of Medicine (T.L., L.-F.L., C.L.), Pathology (D.W., L.T., O.C., H.Z., M.H.Y.C., E.E.), and Surgery (J.M., H.R.), Stanford University, CA. tmclaugh@stanford.edu.
authors.forename: Tracey
authors.initials: T
authors.lastname: McLaughlin
authors.affiliation: From the Departments of Medicine (T.L., L.-F.L., C.L.), Pathology (D.W., L.T., O.C., H.Z., M.H.Y.C., E.E.), and Surgery (J.M., H.R.), Stanford University, CA.
authors.forename: Li-Fen
authors.initials: LF
authors.lastname: Liu
authors.affiliation: From the Departments of Medicine (T.L., L.-F.L., C.L.), Pathology (D.W., L.T., O.C., H.Z., M.H.Y.C., E.E.), and Surgery (J.M., H.R.), Stanford University, CA.
authors.forename: Cindy
authors.initials: C
authors.lastname: Lamendola
authors.affiliation: From the Departments of Medicine (T.L., L.-F.L., C.L.), Pathology (D.W., L.T., O.C., H.Z., M.H.Y.C., E.E.), and Surgery (J.M., H.R.), Stanford University, CA.
authors.forename: Lei
authors.initials: L
authors.lastname: Shen
authors.affiliation: From the Departments of Medicine (T.L., L.-F.L., C.L.), Pathology (D.W., L.T., O.C., H.Z., M.H.Y.C., E.E.), and Surgery (J.M., H.R.), Stanford University, CA.
authors.forename: John
authors.initials: J
authors.lastname: Morton
authors.affiliation: From the Departments of Medicine (T.L., L.-F.L., C.L.), Pathology (D.W., L.T., O.C., H.Z., M.H.Y.C., E.E.), and Surgery (J.M., H.R.), Stanford University, CA.
authors.forename: Homero
authors.initials: H
authors.lastname: Rivas
authors.affiliation: From the Departments of Medicine (T.L., L.-F.L., C.L.), Pathology (D.W., L.T., O.C., H.Z., M.H.Y.C., E.E.), and Surgery (J.M., H.R.), Stanford University, CA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Winer
authors.affiliation: From the Departments of Medicine (T.L., L.-F.L., C.L.), Pathology (D.W., L.T., O.C., H.Z., M.H.Y.C., E.E.), and Surgery (J.M., H.R.), Stanford University, CA.
authors.forename: Lorna
authors.initials: L
authors.lastname: Tolentino
authors.affiliation: From the Departments of Medicine (T.L., L.-F.L., C.L.), Pathology (D.W., L.T., O.C., H.Z., M.H.Y.C., E.E.), and Surgery (J.M., H.R.), Stanford University, CA.
authors.forename: Okmi
authors.initials: O
authors.lastname: Choi
authors.affiliation: From the Departments of Medicine (T.L., L.-F.L., C.L.), Pathology (D.W., L.T., O.C., H.Z., M.H.Y.C., E.E.), and Surgery (J.M., H.R.), Stanford University, CA.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: From the Departments of Medicine (T.L., L.-F.L., C.L.), Pathology (D.W., L.T., O.C., H.Z., M.H.Y.C., E.E.), and Surgery (J.M., H.R.), Stanford University, CA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Hui Yen Chng
authors.affiliation: From the Departments of Medicine (T.L., L.-F.L., C.L.), Pathology (D.W., L.T., O.C., H.Z., M.H.Y.C., E.E.), and Surgery (J.M., H.R.), Stanford University, CA.
authors.forename: Edgar
authors.initials: E
authors.lastname: Engleman
mesh_terms: D000273:Adipose Tissue / Q000276:immunology* / Q000473:pathology; D000328:Adult; D000368:Aged; D000818:Animals; D016207:Cytokines / Q000097:blood / Q000235:genetics; D005260:Female; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018836:Inflammation Mediators / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics / Q000276:immunology*; D050152:Intra-Abdominal Fat / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D009765:Obesity / Q000235:genetics / Q000276:immunology / Q000473:pathology; D050177:Overweight / Q000235:genetics / Q000276:immunology / Q000473:pathology; D050151:Subcutaneous Fat / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators
keywords: C-reactive protein; T helper lymphocytes; T lymphocytes; adaptive immunity; human adipose tissue-specific secretory factor; inflammation; insulin resistance; interleukin-10; interleukin-6; obesity; visceral fat