Obesity-associated improvements in metabolic profile through expansion of adipose tissue
Obesity-associated improvements in metabolic profile through expansion of adipose tissue
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DOI：
10.1172/jci31021
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发表时间：
2007-09-01
影响因子：
15.9
通讯作者：
Scherer, Philipp E.
中科院分区：
文献类型：
--
作者：
Kim, Ja-Young;De Wall, Esther Van;Scherer, Philipp E.
过量的热量摄入会导致胰岛素抵抗。潜在的原因是复杂的，但可能与异位脂质沉积在非脂肪组织。我们假设不能适当地扩张皮下脂肪组织可能是胰岛素抵抗和P细胞衰竭的潜在原因。缺乏瘦素而过表达脂联素的小鼠显示正常的葡萄糖和胰岛素水平，并显着改善葡萄糖以及积极影响血清甘油三酯水平。因此，适度增加循环全长脂联素的水平完全挽救了ob/ob小鼠的糖尿病表型。它们显示出增加的PPAR γ靶基因表达和减少脂肪组织和全身炎症中的巨噬细胞浸润。结果，转基因小鼠是病态肥胖的，脂肪组织的水平显著高于它们的ob/ob同窝出生的小鼠，导致脂肪量增加与胰岛素敏感性改善相关的有趣的二分法。基于这些数据，我们建议，脂联素作为一个外围的“饥饿”信号，促进存储的甘油三酯优先在脂肪组织。因此，肝脏和肌肉中甘油三酯水平的降低可改善全身胰岛素敏感性。因此，这些小鼠代表了我们认为与改善的代谢特征相关的病态肥胖的新模型。
Excess caloric intake can lead to insulin resistance. The underlying reasons are complex but likely related to ectopic lipid deposition in nonadipose tissue. We hypothesized that the inability to appropriately expand subcutaneous adipose tissue may be an underlying reason for insulin resistance and P cell failure. Mice lacking leptin while overexpressing adiponectin showed normalized glucose and insulin levels and dramatically improved glucose as well as positively affected serum triglyceride levels. Therefore, modestly increasing the levels of circulating full-length adiponectin completely rescued the diabetic phenotype in ob/ob mice. They displayed increased expression of PPAR gamma target genes and a reduction in macrophage infiltration in adipose tissue and systemic inflammation. As a result, the transgenic mice were morbidly obese, with significantly higher levels of adipose tissue than their ob/ob littermates, leading to an interesting dichotomy of increased fat mass associated with improvement in insulin sensitivity. Based on these data, we propose that adiponectin acts as a peripheral "starvation" signal promoting the storage of triglycerides preferentially in adipose tissue. As a consequence, reduced triglyceride levels in the liver and muscle convey improved systemic insulin sensitivity. These mice therefore represent what we believe is a novel model of morbid obesity associated with an improved metabolic profile.