T-Cell Profile in Adipose Tissue Is Associated With Insulin Resistance and Systemic Inflammation in Humans

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 34; no. 12; pp. 2637 - 2643
• Main Authors: McLaughlin, Tracey, Liu, Li-Fen, Lamendola, Cindy, Shen, Lei, Morton, John, Rivas, Homero, Winer, Daniel, Tolentino, Lorna, Choi, Okmi, Zhang, Hong, Hui Yen Chng, Melissa, Engleman, Edgar
• Format: Journal Article
• Language: English
• Published: United States American Heart Association, Inc 01.12.2014
• Subjects: Adipose Tissue - immunology; Adipose Tissue - pathology; Adult; Aged; Animals; Cytokines - blood; Cytokines - genetics; Female; Humans; Inflammation - genetics; Inflammation - immunology; Inflammation - pathology; Inflammation Mediators - blood; Insulin Resistance - genetics; Insulin Resistance - immunology; Intra-Abdominal Fat - immunology; Intra-Abdominal Fat - pathology; Male; Mice; Middle Aged; Obesity - genetics; Obesity - immunology; Obesity - pathology; Overweight - genetics; Overweight - immunology; Overweight - pathology; Subcutaneous Fat - immunology; Subcutaneous Fat - pathology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - pathology; T lymphocytes; C-reactive protein; T helper lymphocytes; inflammation; insulin resistance; interleukin-10; visceral fat; adaptive immunity; interleukin-6; obesity; human adipose tissue-specific secretory factor
• DOI: 10.1161/ATVBAHA.114.304636
• ISSN: 1079-5642; 1524-4636

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. APPROACH AND 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.