title: Association between specific adipose tissue CD4+ T-cell populations and insulin resistance in obese individuals.
abstract: OBJECTIVE
  An increased number of macrophages in adipose tissue is associated with insulin resistance and metabolic dysfunction in obese people. However, little is known about other immune cells in adipose tissue from obese people, and whether they contribute to insulin resistance. We investigated the characteristics of T cells in adipose tissue from metabolically abnormal insulin-resistant obese (MAO) subjects, metabolically normal insulin-sensitive obese (MNO) subjects, and lean subjects. Insulin sensitivity was determined by using the hyperinsulinemic euglycemic clamp procedure.
  
  
  METHODS
  We assessed plasma cytokine concentrations and subcutaneous adipose tissue CD4(+) T-cell populations in 9 lean, 12 MNO, and 13 MAO subjects. Skeletal muscle and liver samples were collected from 19 additional obese patients undergoing bariatric surgery to determine the presence of selected cytokine receptors.
  
  
  RESULTS
  Adipose tissue from MAO subjects had 3- to 10-fold increases in numbers of CD4(+) T cells that produce interleukin (IL)-22 and IL-17 (a T-helper [Th] 17 and Th22 phenotype) compared with MNO and lean subjects. MAO subjects also had increased plasma concentrations of IL-22 and IL-6. Receptors for IL-17 and IL-22 were expressed in human liver and skeletal muscle samples. IL-17 and IL-22 inhibited uptake of glucose in skeletal muscle isolated from rats and reduced insulin sensitivity in cultured human hepatocytes.
  
  
  CONCLUSIONS
  Adipose tissue from MAO individuals contains increased numbers of Th17 and Th22 cells, which produce cytokines that cause metabolic dysfunction in liver and muscle in vitro. Additional studies are needed to determine whether these alterations in adipose tissue T cells contribute to the pathogenesis of insulin resistance in obese people.
authors.affiliation: Center for Human Nutrition, Washington University School of Medicine, St Louis, Missouri 63110, USA.
authors.forename: Elisa
authors.initials: E
authors.lastname: Fabbrini
authors.forename: Marina
authors.initials: M
authors.lastname: Cella
authors.forename: Steve A
authors.initials: SA
authors.lastname: McCartney
authors.forename: Anja
authors.initials: A
authors.lastname: Fuchs
authors.forename: Nada A
authors.initials: NA
authors.lastname: Abumrad
authors.forename: Terri A
authors.initials: TA
authors.lastname: Pietka
authors.forename: Zhouji
authors.initials: Z
authors.lastname: Chen
authors.forename: Brian N
authors.initials: BN
authors.lastname: Finck
authors.forename: Dong Ho
authors.initials: DH
authors.lastname: Han
authors.forename: Faidon
authors.initials: F
authors.lastname: Magkos
authors.forename: Caterina
authors.initials: C
authors.lastname: Conte
authors.forename: David
authors.initials: D
authors.lastname: Bradley
authors.forename: Gemma
authors.initials: G
authors.lastname: Fraterrigo
authors.forename: J Christopher
authors.initials: JC
authors.lastname: Eagon
authors.forename: Bruce W
authors.initials: BW
authors.lastname: Patterson
authors.forename: Marco
authors.initials: M
authors.lastname: Colonna
authors.forename: Samuel
authors.initials: S
authors.lastname: Klein
mesh_terms: D000328:Adult; D000818:Animals; D015992:Body Mass Index; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016022:Case-Control Studies; D016207:Cytokines / Q000276:immunology*; D005260:Female; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D007333:Insulin Resistance / Q000276:immunology*; D020381:Interleukin-17 / Q000378:metabolism / Q000494:pharmacology; D015850:Interleukin-6 / Q000097:blood; D007378:Interleukins / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009765:Obesity / Q000276:immunology* / Q000378:metabolism; D051381:Rats; D018123:Receptors, Interleukin / Q000378:metabolism; D053722:Receptors, Interleukin-17 / Q000378:metabolism; D050151:Subcutaneous Fat / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D016207:Cytokines; D005947:Glucose; D020381:Interleukin-17; D015850:Interleukin-6; D007378:Interleukins; D018123:Receptors, Interleukin; D053722:Receptors, Interleukin-17; D000097043:Interleukin-22; C109985:IL17RA protein, human; C508600:IL6 protein, human; C415369:interleukin-22 receptor
keywords: FFM; GIF; IFN; IL; JNK; Lymphocytes; MAO; MNO; Metabolically Abnormal Obesity; Metabolically Normal Obesity; NAFLD; c-Jun kinase; fat free mass; glucose infusion rate; interferon; interleukin; metabolically abnormal insulin-resistant obese; metabolically normal insulin-sensitive obese; nonalcoholic fatty liver disease