IL-6 and IL-10 Anti-Inflammatory Activity Links Exercise to Hypothalamic Insulin and Leptin Sensitivity through IKKβ and ER Stress Inhibition (Retracted Article)
IL-6 and IL-10 Anti-Inflammatory Activity Links Exercise to Hypothalamic Insulin and Leptin Sensitivity through IKKβ and ER Stress Inhibition (Retracted Article)
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DOI：
10.1371/journal.pbio.1000465
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发表时间：
2010-08-01
期刊：
影响因子：
9.8
通讯作者：
Carvalheira, Jose B. C.
中科院分区：
文献类型：
--
作者：
Ropelle, Eduardo R.;Flores, Marcelo B.;Carvalheira, Jose B. C.
暴饮暴食引起的营养过剩通过IKK β激活和下丘脑内质网（ER）应激与胰岛素和瘦素抵抗相关。在这里，我们表明，体育锻炼抑制暴食症和相关的下丘脑IKK β/NF-κ β激活的机制依赖于促炎细胞因子白细胞介素（IL）-6。下丘脑特异性IL-6作用的破坏阻断了运动对食物摄入和胰岛素及瘦素抵抗的再平衡的有益作用。这种由身体活动介导的分子机制涉及抗炎蛋白IL-10，它是IKK β/NF-k β信号传导和ER应激的核心抑制剂。我们报告说，运动和重组IL-6需要IL-10的表达，以抑制过度吞噬相关的肥胖。此外，与对照小鼠相比，运动未能逆转下丘脑IL-6和IL-10信号转导缺陷的C3 H/HeJ小鼠中IKK β和ER应激的药理学激活。因此，下丘脑中的炎症信号将运动的有益生理效应与胰岛素和瘦素的中枢作用联系起来。
Overnutrition caused by overeating is associated with insulin and leptin resistance through IKK beta activation and endoplasmic reticulum (ER) stress in the hypothalamus. Here we show that physical exercise suppresses hyperphagia and associated hypothalamic IKK beta/NF-k beta activation by a mechanism dependent upon the pro-inflammatory cytokine interleukin (IL)-6. The disruption of hypothalamic-specific IL-6 action blocked the beneficial effects of exercise on the re-balance of food intake and insulin and leptin resistance. This molecular mechanism, mediated by physical activity, involves the anti-inflammatory protein IL-10, a core inhibitor of IKK beta/NF-k beta signaling and ER stress. We report that exercise and recombinant IL-6 requires IL-10 expression to suppress hyperphagia-related obesity. Moreover, in contrast to control mice, exercise failed to reverse the pharmacological activation of IKK beta and ER stress in C3H/HeJ mice deficient in hypothalamic IL-6 and IL-10 signaling. Hence, inflammatory signaling in the hypothalamus links beneficial physiological effects of exercise to the central action of insulin and leptin.