Department of Medicine, Interdisciplinary Centre for Clinical Research, University of Leipzig, Germany.
Am J Physiol Endocrinol Metab. 2010 Sep;299(3):E506-15. doi: 10.1152/ajpendo.00586.2009. Epub 2010 Jun 22.
The association between obesity and impaired insulin sensitivity has long been recognized, although a subgroup of obese individuals seems to be protected from insulin resistance. In this study, we systematically studied differences in adipose tissue biology between insulin-sensitive (IS) and insulin-resistant (IR) individuals with morbid obesity. On the basis of glucose infusion rate during euglycemic hyperinsulinemic clamps, 60 individuals with a BMI of 45 +/- 1.3 kg/m(2) were divided into an IS and IR group matched for age, sex, and body fat prior to elective surgery. We measured fat distribution, circulating adipokines, and parameters of inflammation, glucose, and lipid metabolism and characterized adipose tissue morphology, function, and mRNA expression in abdominal subcutaneous (sc) and omental fat. IS compared with IR obese individuals have significantly lower visceral fat area (138 +/- 27 vs. 316 +/- 91 cm(2)), number of macrophages in omental adipose tissue (4.9 +/- 0.8 vs. 13.2 +/- 1.4%), mean omental adipocyte size (528 +/- 76 vs. 715 +/- 81 pl), circulating C-reactive protein, progranulin, chemerin, and retinol-binding protein-4 (all P values <0.05), and higher serum adiponectin (6.9 +/- 3.4 vs. 3.4 +/- 1.7 ng/ml) and omental adipocyte insulin sensitivity (all P values <0.01). The strongest predictors of insulin sensitivity by far were macrophage infiltration together with circulating adiponectin (r(2) = 0.98, P < 0.0001). In conclusion, independently of total body fat mass, increased visceral fat accumulation and adipose tissue dysfunction are associated with IR obesity. This suggests that mechanisms beyond a positive caloric balance such as inflammation and adipokine release determine the pathological metabolic consequences in patients with obesity.
肥胖与胰岛素敏感性受损之间的关联早已被认识到，尽管肥胖人群中有一部分似乎对胰岛素抵抗有保护作用。在这项研究中，我们系统地研究了病态肥胖的胰岛素敏感（IS）和胰岛素抵抗（IR）个体之间脂肪组织生物学的差异。根据在正常血糖高胰岛素钳夹期间的葡萄糖输注率，将 60 名 BMI 为 45 ± 1.3 kg/m2 的个体分为 IS 和 IR 组，这些个体在接受择期手术前按年龄、性别和体脂进行匹配。我们测量了脂肪分布、循环脂肪因子以及炎症、葡萄糖和脂质代谢的参数，并对腹部皮下（sc）和网膜脂肪的脂肪组织形态、功能和 mRNA 表达进行了特征描述。与 IR 肥胖个体相比，IS 肥胖个体的内脏脂肪面积显著降低（138 ± 27 对 316 ± 91 cm2），网膜脂肪组织中的巨噬细胞数量减少（4.9 ± 0.8 对 13.2 ± 1.4%），网膜脂肪细胞的平均大小减小（528 ± 76 对 715 ± 81 pl），循环 C 反应蛋白、颗粒蛋白、趋化素和视黄醇结合蛋白 4（所有 P 值均 <0.05）升高，血清脂联素升高（6.9 ± 3.4 对 3.4 ± 1.7 ng/ml），网膜脂肪细胞对胰岛素的敏感性增加（所有 P 值均 <0.01）。到目前为止，胰岛素敏感性的最强预测因子是巨噬细胞浸润和循环脂联素（r2 = 0.98，P < 0.0001）。总之，除了总体脂肪量之外，内脏脂肪的积累增加和脂肪组织功能障碍与 IR 肥胖有关。这表明，决定肥胖患者发生病理性代谢后果的机制不仅仅是热量摄入的正平衡，还包括炎症和脂肪因子的释放等因素。
