mTORC1 in AGRP neurons integrates exteroceptive and interoceptive food-related cues in the modulation of adaptive energy expenditure in mice
mTORC1 in AGRP neurons integrates exteroceptive and interoceptive food-related cues in the modulation of adaptive energy expenditure in mice
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DOI：
10.1101/110544
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发表时间：
2017-02
期刊：
影响因子：
7.7
通讯作者：
L. K. Burke;Tamana Darwish;Althea R. Cavanaugh;S. Virtue;Emma Roth;Joanna Morro;Shun-Mei Liu;Jing Xia;J. Dalley;K. Burling;S. Chua;Toni Vidal-Puig;G. Schwartz;C. Blouet
中科院分区：
文献类型：
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作者：
L. K. Burke;Tamana Darwish;Althea R. Cavanaugh;S. Virtue;Emma Roth;Joanna Morro;Shun-Mei Liu;Jing Xia;J. Dalley;K. Burling;S. Chua;Toni Vidal-Puig;G. Schwartz;C. Blouet
通过肩胛间棕色脂肪组织（iBAT）产热的能量耗散是适应性能量消耗的重要贡献者。然而，大脑如何检测能量可用性的急性和慢性变化以调节iBAT活性并维持能量稳态仍然是未解决的。在这里，我们提供的证据表明，AGRP抑制音iBAT代表了一个节省能源的电路，整合环境的食物线索和内部信号的能量可用性。我们在AGRP神经元内建立了营养感应mTORC1信号通路在检测环境食物线索和能量可用性的内部信号中的作用，以及在营养缺乏和过量期间iBAT产热的双向控制中的作用。总的来说，我们的研究结果提供了对AGRP神经元内mTORC 1信号传导如何调查能量可用性以参与iBAT产热的见解，并将AGRP神经元确定为在不同生理和环境背景下协调能量摄入和适应性支出的神经元底物。
Energy dissipation through interscapular brown adipose tissue (iBAT) thermogenesis is an important contributor to adaptive energy expenditure. However, it remains unresolved how acute and chronic changes in energy availability are detected by the brain to adjust iBAT activity and maintain energy homeostasis. Here we provide evidence that AGRP inhibitory tone to iBAT represents an energy-sparing circuit that integrates environmental food cues and internal signals of energy availability. We establish a role for the nutrient-sensing mTORC1 signaling pathway within AGRP neurons in the detection of environmental food cues and internal signals of energy availability, and in the bi-directional control of iBAT thermogenesis during nutrient deficiency and excess. Collectively, our findings provide insights into how mTORC1 signaling within AGRP neurons surveys energy availability to engage iBAT thermogenesis, and identify AGRP neurons as a neuronal substrate for the coordination of energy intake and adaptive expenditure under varying physiological and environmental contexts.