title: Obesity is associated with activated and insulin resistant immune cells.
abstract: BACKGROUND
  Obesity and type 2 diabetes mellitus are characterized by insulin resistance and 'low-grade inflammation'; however, the pathophysiological link is poorly understood. To determine the relative contribution of obesity and insulin resistance to systemic 'inflammation', this study comprehensively characterized circulating immune cells in different grades of obesity.
  
  
  METHODS
  Immune cell phenotypes and activation status were analysed by flow cytometry cross-sectionally in morbidly obese (n = 16, body mass index (BMI) 42.2 ± 5.4 kg/m2), overweight (n = 13, BMI 27.4 ± 1.6 kg/m2) and normal weight (n = 12, BMI 22.5 ± 1.9 kg/m2) subjects.
  
  
  RESULTS
  Obese, but not overweight subjects, had increased activation marker expression on neutrophils, monocytes, T-lymphocytes and polarization of T helper cells towards a pro-inflammatory type 1-phenotype (Th1). Th1 numbers correlated positively with the degree of insulin resistance (homeostasis model assessment, p < 0.05). Lymphocytes from obese subjects showed reduced insulin-stimulated AKT-phosphorylation in vitro. Supra-physiological insulin concentrations did not affect T-cell differentiation, which under normal circumstances would promote an anti-inflammatory T helper type 2-phenotype.
  
  
  CONCLUSIONS
  These results show that morbid obesity is characterized by circulating immune cells that are activated and insulin resistant, with the T-cell balance polarized towards a pro-inflammatory Th1 phenotype. The loss of insulin-induced suppression of inflammatory phenotypes in circulating immune cells could contribute to the systemic and adipose tissue inflammation found in morbid obesity.
authors.affiliation: Diabetes and Obesity Research Program, Garvan Institute of Medical Research, Sydney-Darlinghurst, NSW 2010, Australia. a.viardot@garvan.org.au
authors.forename: A
authors.initials: A
authors.lastname: Viardot
authors.forename: L K
authors.initials: LK
authors.lastname: Heilbronn
authors.forename: D
authors.initials: D
authors.lastname: Samocha-Bonet
authors.forename: F
authors.initials: F
authors.lastname: Mackay
authors.forename: L V
authors.initials: LV
authors.lastname: Campbell
authors.forename: K
authors.initials: K
authors.lastname: Samaras
mesh_terms: D000273:Adipose Tissue / Q000276:immunology / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism*; D001823:Body Composition; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009767:Obesity, Morbid / Q000150:complications*; D050177:Overweight / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D007328:Insulin