Regulation of energy rheostasis by the melanocortin-3 receptor.
Regulation of energy rheostasis by the melanocortin-3 receptor.
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DOI：
10.1126/sciadv.aat0866
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发表时间：
2018-08
期刊：
影响因子：
13.6
通讯作者：
Cone RD
中科院分区：
文献类型：
--
作者：
Ghamari-Langroudi M;Cakir I;Lippert RN;Sweeney P;Litt MJ;Ellacott KLJ;Cone RD
黑素皮质素-3受体通过突触前抑制MC4R神经元的活动，对能量平衡起到变阻器的作用。像大多数动态平衡系统一样，哺乳动物的肥胖症是在上下限条件之间进行防御的。虽然瘦素和黑素皮质素-4受体(MC4R)信号是保卫能量设定点所必需的，但控制体内平衡上下边界的机制还不太清楚。与MC4R不同，MC3R的缺失在正常情况下不会产生明显的吞噬功能亢进或代谢低下。然而，我们证明了MC3R是双向需要的，以控制对外部动态平衡挑战的反应，例如卡路里限制或高热量饮食。在怀孕期间，MC3R也是调节偏离设定点或血液流变性的必需品。进一步，我们证明了一个分子机制：MC3R为黑素皮质素信号提供调节输入，作用于刺鼠相关蛋白神经元的突触前，调节γ-氨基丁酸释放到厌食的MC4R神经元，对MC4R神经元的活动实施边界控制。因此，MC3R是黑素皮质素信号的边界控制的关键调节器，提供能量储存的阻力控制。
The melanocortin-3 receptor acts as a rheostat on energy homeostasis through presynaptic inhibition of MC4R neuronal activity. Like most homeostatic systems, adiposity in mammals is defended between upper and lower boundary conditions. While leptin and melanocortin-4 receptor (MC4R) signaling are required for defending energy set point, mechanisms controlling upper and lower homeostatic boundaries are less well understood. In contrast to the MC4R, deletion of the MC3R does not produce measurable hyperphagia or hypometabolism under normal conditions. However, we demonstrate that MC3R is required bidirectionally for controlling responses to external homeostatic challenges, such as caloric restriction or calorie-rich diet. MC3R is also required for regulated excursion from set point, or rheostasis, during pregnancy. Further, we demonstrate a molecular mechanism: MC3R provides regulatory inputs to melanocortin signaling, acting presynaptically on agouti-related protein neurons to regulate γ-aminobutyric acid release onto anorexigenic MC4R neurons, exerting boundary control on the activity of MC4R neurons. Thus, the MC3R is a critical regulator of boundary controls on melanocortin signaling, providing rheostatic control on energy storage.
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影响因子：
64.8
作者：
Ghamari-Langroudi M;Digby GJ;Sebag JA;Millhauser GL;Palomino R;Matthews R;Gillyard T;Panaro BL;Tough IR;Cox HM;Denton JS;Cone RD
通讯作者：
Cone RD
影响因子：
15.9
作者：
Cheung, W;Yu, PX;Mak, RH
通讯作者：
Mak, RH
影响因子：
64.8
作者：
Fan, W;Boston, BA;Cone, RD
通讯作者：
Cone, RD
影响因子：
5.3
作者：
Liu, HY;Kishi, T;Elmquist, JK
通讯作者：
Elmquist, JK
DOI：
10.1111/j.1749-6632.2003.tb03188.x
发表时间：
2003-01-01
期刊：
MELANOCORTIN SYSTEM
影响因子：
--
作者：
Marks, DL;Cone, RD
通讯作者：
Cone, RD