Obesity causes selective and long-lasting desensitization of AgRP neurons to dietary fat
Obesity causes selective and long-lasting desensitization of AgRP neurons to dietary fat
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DOI：
10.7554/elife.55909
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发表时间：
2020-07-28
期刊：
影响因子：
7.7
通讯作者：
Knight, Zachary A.
中科院分区：
文献类型：
--
作者：
Beutler, Lisa R.;Corpuz, Timothy, V;Knight, Zachary A.
体重是由追踪能量需求的感觉间神经回路来调节的，但这些回路的活动在肥胖中是如何改变的，仍然知之甚少。在这里，我们描述了在饮食诱导的肥胖小鼠发展过程中促进饥饿的AgRP神经元的体内动力学。我们发现，高脂饮食减弱了AgRP神经元对一系列营养相关刺激的反应，包括食物暗示、胃内营养物质、CCK和Ghrelin。这些变化是特定于饮食脂肪的，而不是碳水化合物或蛋白质。随后的体重减轻恢复了AgRP神经元对外界感觉提示的反应性，但无法挽救它们对胃肠激素或营养的敏感性。这些发现揭示了肥胖触发了下丘脑饥饿神经元的广泛失调，这种失调不能被体重减轻完全逆转，并可能导致维持减轻体重的困难。
Body weight is regulated by interoceptive neural circuits that track energy need, but how the activity of these circuits is altered in obesity remains poorly understood. Here we describe the in vivo dynamics of hunger-promoting AgRP neurons during the development of diet-induced obesity in mice. We show that high-fat diet attenuates the response of AgRP neurons to an array of nutritionally-relevant stimuli including food cues, intragastric nutrients, cholecystokinin and ghrelin. These alterations are specific to dietary fat but not carbohydrate or protein. Subsequent weight loss restores the responsiveness of AgRP neurons to exterosensory cues but fails to rescue their sensitivity to gastrointestinal hormones or nutrients. These findings reveal that obesity triggers broad dysregulation of hypothalamic hunger neurons that is incompletely reversed by weight loss and may contribute to the difficulty of maintaining a reduced weight.