Obesity is associated with activated and insulin resistant immune cells
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. Copyright (c) 2012 John Wiley & Sons, Ltd.
|ISBN||1520-7560 (Electronic) 1520-7552 (Linking)|
|Authors||Viardot, A.; Heilbronn, L. K.; Samocha-Bonet, D.; Mackay, F.; Campbell, L. V.; Samaras, K.;|
|Publisher Name||DIABETES-METAB RES|
|Published Date||2012-01-01 00:00:00|