Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Surg Obes Relat Dis. 2011 Jan-Feb;7(1):60-7. doi: 10.1016/j.soard.2010.05.013. Epub 2010 Jun 1.
Obesity is a strong risk factor for resistance to insulin-mediated glucose disposal, a precursor of type 2 diabetes and other disorders. However, not all obese individuals are insulin resistant. We sought to identify the molecular pathways that might cause obesity-associated insulin resistance in humans by studying the morbidly obese who were insulin sensitive versus insulin resistant, thereby eliminating obesity as a variable.
Combining gene expression profiling with computational approaches, we determined the global gene expression signatures of omental and subcutaneous adipose tissue samples obtained from similarly obese patients undergoing gastric bypass surgery.
Gene sets related to chemokine activity and chemokine receptor binding were identified as most highly expressed in the omental tissue from insulin-resistant compared with insulin-sensitive subjects, independent of the body mass index. These upregulated genes included chemokines (C-C motif) ligand 2, 3, 4, and 18 and interleukin-8/(CC-X motif) ligand 8 and were not differentially expressed in the subcutaneous adipose tissues between the 2 groups of subjects. Insulin resistance, but not the body mass index, was associated with increased macrophage infiltration in the omental adipose tissue, as was adipocyte size, in these morbidly obese subjects.
Our findings have demonstrated that inflammation of the omental adipose tissue is strongly associated with insulin resistance in human obesity even in subjects with similar body mass index values.
肥胖是机体对胰岛素介导的葡萄糖摄取产生抵抗的一个强有力的风险因素，而后者是 2 型糖尿病和其他疾病的前期表现。然而，并非所有肥胖个体均存在胰岛素抵抗。我们试图通过研究对胰岛素敏感与抵抗的病态肥胖个体来确定导致人类肥胖相关胰岛素抵抗的分子途径，从而消除肥胖这一变量。
我们结合基因表达谱和计算方法，对接受胃旁路手术的肥胖患者的大网膜和皮下脂肪组织样本进行了研究，以确定其全球基因表达特征。
结果发现，与胰岛素敏感的患者相比，与趋化因子活性和趋化因子受体结合相关的基因集在胰岛素抵抗患者的大网膜组织中表达最高，而与体重指数无关。这些上调的基因包括趋化因子（C-C 基序）配体 2、3、4 和 18 以及白细胞介素 8/（CC-X 基序）配体 8，在两组患者的皮下脂肪组织中并未表现出差异表达。在这些病态肥胖患者中，胰岛素抵抗而非体重指数与大网膜脂肪组织中巨噬细胞浸润的增加有关，与脂肪细胞大小也有关。
我们的研究结果表明，即使在体重指数相似的患者中，大网膜脂肪组织的炎症也与人类肥胖中的胰岛素抵抗密切相关。
