Lipid-Overloaded Enlarged Adipocytes Provoke Insulin Resistance Independent of Inflammation
Lipid-Overloaded Enlarged Adipocytes Provoke Insulin Resistance Independent of Inflammation
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DOI：
10.1128/mcb.01321-14
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发表时间：
2015-05-01
影响因子：
5.3
通讯作者：
Kim, Jae Bum
中科院分区：
文献类型：
--
作者：
Kim, Jong In;Huh, Jin Young;Kim, Jae Bum
在肥胖中，脂肪细胞肥大和促炎反应与脂肪组织中胰岛素抵抗的发展密切相关。然而，脂肪细胞肥大本身是否足以引起肥胖脂肪组织的胰岛素抵抗在很大程度上是未知的。在这里，我们证明脂质超载的肥厚脂肪细胞是胰岛素抵抗独立于脂肪细胞炎症。用饱和脂肪酸或单不饱和脂肪酸处理导致脂肪细胞肥大，但促炎反应仅在饱和脂肪酸处理的脂肪细胞中观察到。无论脂肪细胞炎症如何，具有大且单眼脂滴的肥厚脂肪细胞表现出胰岛素依赖性葡萄糖摄取受损，这与GLUT4转运到质膜的缺陷有关。此外，高脂饮食诱导肥胖的toll样受体4突变小鼠（C3H/HeJ）虽然对脂肪组织炎症有抵抗性，但对胰岛素抵抗没有保护作用。总之，我们的体外和体内数据表明，脂肪细胞肥大本身可能是导致肥胖患者胰岛素抵抗的关键。
In obesity, adipocyte hypertrophy and proinflammatory responses are closely associated with the development of insulin resistance in adipose tissue. However, it is largely unknown whether adipocyte hypertrophy per se might be sufficient to provoke insulin resistance in obese adipose tissue. Here, we demonstrate that lipid-overloaded hypertrophic adipocytes are insulin resistant independent of adipocyte inflammation. Treatment with saturated or monounsaturated fatty acids resulted in adipocyte hypertrophy, but proinflammatory responses were observed only in adipocytes treated with saturated fatty acids. Regardless of adipocyte inflammation, hypertrophic adipocytes with large and unilocular lipid droplets exhibited impaired insulin-dependent glucose uptake, associated with defects in GLUT4 trafficking to the plasma membrane. Moreover, Toll-like receptor 4 mutant mice (C3H/HeJ) with high-fat-diet-induced obesity were not protected against insulin resistance, although they were resistant to adipose tissue inflammation. Together, our in vitro and in vivo data suggest that adipocyte hypertrophy alone may be crucial in causing insulin resistance in obesity.