Obesity is associated with hypothalamic injury in rodents and humans
Obesity is associated with hypothalamic injury in rodents and humans
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DOI：
10.1172/jci59660
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发表时间：
2012-01-01
影响因子：
15.9
通讯作者：
Schwartz, Michael W.
中科院分区：
文献类型：
--
作者：
Thaler, Joshua P.;Yi, Chun-Xia;Schwartz, Michael W.
通过消耗高脂饮食（HFD）诱导的肥胖的啮齿动物模型的特征在于外周组织和对能量稳态至关重要的下丘脑区域中的炎症。在这里，我们报告说，不像周围组织中的炎症，这是肥胖的结果，下丘脑炎症信号是明显的，在大鼠和小鼠HFD发作的1至3天内，在大量的体重增加。此外，在喂食HFD的第一周内，大鼠和小鼠的下丘脑弓状核中反应性胶质增生和提示神经元损伤的标记物都很明显。虽然这些反应暂时消退，表明神经保护机制可能最初限制的损害，持续HFD喂养，炎症和神经胶质增生永久返回到下丘脑内侧基底。与啮齿类动物中的这些数据一致，我们发现了肥胖人类中基底下丘脑神经胶质增生增加的证据，如MRI所评估的。这些发现共同表明，在人类和啮齿动物模型中，肥胖与对体重控制至关重要的大脑区域的神经元损伤有关。
Rodent models of obesity induced by consuming high-fat diet (HFD) are characterized by inflammation both in peripheral tissues and in hypothalamic areas critical for energy homeostasis. Here we report that unlike inflammation in peripheral tissues, which develops as a consequence of obesity, hypothalamic inflammatory signaling was evident in both rats and mice within 1 to 3 days of HFD onset, prior to substantial weight gain. Furthermore, both reactive gliosis and markers suggestive of neuron injury were evident in the hypothalamic arcuate nucleus of rats and mice within the first week of HFD feeding. Although these responses temporarily subsided, suggesting that neuroprotective mechanisms may initially limit the damage, with continued HFD feeding, inflammation and gliosis returned permanently to the mediobasal hypothalamus. Consistent with these data in rodents, we found evidence of increased gliosis in the mediobasal hypothalamus of obese humans, as assessed by MRI. These findings collectively suggest that, in both humans and rodent models, obesity is associated with neuronal injury in a brain area crucial for body weight control.