T-cell profile in adipose tissue is associated with insulin resistance and systemic inflammation in humans.
T-cell profile in adipose tissue is associated with insulin resistance and systemic inflammation in humans.
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DOI：
10.1161/atvbaha.114.304636
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发表时间：
2014-12
期刊：
影响因子：
--
通讯作者：
Engleman E
中科院分区：
文献类型：
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作者：
McLaughlin T;Liu LF;Lamendola C;Shen L;Morton J;Rivas H;Winer D;Tolentino L;Choi O;Zhang H;Hui Yen Chng M;Engleman E
肥胖与胰岛素抵抗的生物学机制尚未完全阐明。我们已经证明，饮食诱导的肥胖小鼠的胰岛素抵抗/葡萄糖耐受不良与脂肪组织中促炎性和抗炎性T细胞比例的变化有关。我们试图检验T细胞表型的平衡与人类肥胖中的胰岛素抵抗类似相关的假设。健康超重/肥胖人类受试者接受脂肪组织活检，并通过改良的胰岛素抑制试验定量胰岛素介导的葡萄糖处置。通过流式细胞术定量内脏（VAT）和皮下脂肪组织（SAT）中的T细胞亚群。结果表明，CD 4和CD 8 T细胞浸润两个仓库，与促炎性辅助性T细胞（Th）-1，Th 17和CD 8 T细胞显着更频繁的VAT相比，SAT。SAT和VAT中的T细胞谱彼此之间以及与外周血显著相关。SAT和VAT中的Th 1频率与血浆hsCRP浓度呈正相关，而VAT中的Th 2频率与血浆hsCRP浓度呈负相关。SAT中Th 1与血浆IL-6相关。储库和外周血中的Th 2与全身胰岛素抵抗呈负相关。通过rtPCR测量的相关细胞因子的相对表达反映了流式细胞术结果。最值得注意的是，脂肪组织白细胞介素-10的表达与胰岛素抵抗呈负相关。CD 4和CD 8 T细胞分布在人类脂肪组织中，Th 1和Th 2的相对频率与全身性炎症和胰岛素抵抗高度相关。这些发现指出适应性免疫系统是肥胖和胰岛素抵抗/炎症之间的潜在媒介。识别脂肪组织中的抗原刺激物可能产生治疗肥胖相关代谢疾病的新靶点。
The biological mechanisms linking obesity to insulin resistance have not been fully elucidated. We have shown that insulin resistance/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. Healthy overweight/obese human subjects underwent adipose-tissue biopsies and quantification of insulin-mediated-glucose disposal by the modified insulin-suppression test. T-cell subsets were quantitated by flow cytometry in visceral (VAT) and subcutaneous adipose tissue (SAT). Results showed that CD4 and CD8 T-cells infiltrate both depots, with pro-inflammatory 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 hsCRP concentrations. Th1 in SAT correlated with plasma interleukin-6. Th2 in both depots and peripheral blood was inversely associated with systemic insulin resistance. Relative expression of associated cytokines, measured by rtPCR, reflected flow cytometry results. Most notably, adipose tissue expression of interleukin-10 was inversely associated with insulin resistance. CD4 and CD8 T-cells populate human adipose tissue and the relative frequency of Th1 and Th2 is 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/inflammation. Identification of antigenic stimuli in adipose tissue may yield novel targets for treatment of obesity-associated metabolic disease.