Denis R G P, Joly-Amado A, Cansell C, Castel J, Martinez S, Delbes A S, Luquet S
Unité « biologie fonctionnelle et adaptative » (BFA), université Paris Diderot-Paris 7, CNRS EAC 4413, 4, rue Marie-Andrée-Lagroua-Weill-Hallé, bâtiment Buffon, case courrier 7126, 75205 Paris cedex 13, France.
Unité « biologie fonctionnelle et adaptative » (BFA), université Paris Diderot-Paris 7, CNRS EAC 4413, 4, rue Marie-Andrée-Lagroua-Weill-Hallé, bâtiment Buffon, case courrier 7126, 75205 Paris cedex 13, France; Centre national de la recherche scientifique-CNRS, EAC 4413, 75205 Paris, France.
Diabetes Metab. 2014 Jun;40(3):191-7. doi: 10.1016/j.diabet.2013.11.002. Epub 2013 Dec 11.
Energy homoeostasis is maintained through a complex interplay of nutrient intake and energy expenditure. The central nervous system is an essential component of this regulation, as it integrates circulating signals of hunger and satiety to develop adaptive responses at the behavioural and metabolic levels, while the hypothalamus is regarded as a particularly crucial structure in the brain in terms of energy homoeostasis. The arcuate nucleus (ARC) of the hypothalamus contains at least two intermingled neuronal populations: the neurons that produce neuropeptide Y (NPY); and the Agouti-related protein (AgRP) produced by AgRP/NPY neurons situated below the third ventricle in close proximity to proopiomelanocortin (POMC)-producing neurons. POMC neurons exert their catabolic and anorectic actions by releasing α-melanocyte-stimulating hormone (α-MSH), while AgRP neurons oppose this action by exerting tonic GABAergic inhibition of POMC neurons and releasing the melanocortin receptor inverse agonist AgRP. The release of neurotransmitters and neuropeptides by second-order AgRP neurons appears to take place on a multiple time scale, thereby allowing neuromodulation of preganglionic neuronal activity and subsequent control of nutrient partitioning - in other words, the coordinated regulation of conversion, storage and utilization of carbohydrates vs. lipids. This suggests that the function of AgRP neurons extends beyond the strict regulation of feeding to the regulation of efferent organ activity, such that AgRP neurons may now be viewed as an important bridge between central detection of nutrient availability and peripheral nutrient partitioning, thus providing a mechanistic link between obesity and obesity-related disorders.
能量稳态通过营养物质摄入与能量消耗之间复杂的相互作用得以维持。中枢神经系统是这种调节的重要组成部分，因为它整合饥饿和饱腹感的循环信号，以在行为和代谢水平上产生适应性反应，而下丘脑在能量稳态方面被认为是大脑中一个特别关键的结构。下丘脑的弓状核（ARC）至少包含两种相互交织的神经元群体：产生神经肽Y（NPY）的神经元；以及由位于第三脑室下方、紧邻产生阿黑皮素原（POMC）的神经元的AgRP/NPY神经元产生的刺鼠相关蛋白（AgRP）。POMC神经元通过释放α-黑素细胞刺激素（α-MSH）发挥其分解代谢和厌食作用，而AgRP神经元则通过对POMC神经元施加持续性GABA能抑制并释放黑素皮质素受体反向激动剂AgRP来对抗这种作用。二级AgRP神经元释放神经递质和神经肽的过程似乎发生在多个时间尺度上，从而允许对节前神经元活动进行神经调节，并随后控制营养物质的分配——换句话说，对碳水化合物与脂质的转化、储存和利用进行协调调节。这表明AgRP神经元的功能超出了对进食的严格调节，扩展到对传出器官活动的调节，因此现在可以将AgRP神经元视为中枢对营养物质可利用性的检测与外周营养物质分配之间的重要桥梁，从而为肥胖症及肥胖相关疾病提供了一种机制上的联系。
