Levin Barry E
Neurology Service (127C), VA Medical Center, 385 Tremont Ave., E. Orange, NJ 07018-1095, USA.
Physiol Behav. 2006 Nov 30;89(4):486-9. doi: 10.1016/j.physbeh.2006.07.003. Epub 2006 Aug 8.
The brain and periphery carry on a constant conversation; the periphery informs the brain about its metabolic needs and the brain provides for these needs through its control of somatomotor, autonomic and neurohumoral pathways involved in energy intake, expenditure and storage. Metabolic sensing neurons are the integrators of a variety of metabolic, humoral and neural inputs from the periphery. Such neurons, originally called "glucosensing", also respond to fatty acids, hormones and metabolites from the periphery. They are integrated within neural pathways involved in the regulation of energy homeostasis. Unlike most neurons, they utilize glucose and other metabolites as signaling molecules to regulate their membrane potential and firing rate. For glucosensing neurons, glucokinase acts as the rate-limiting step in glucosensing while the pathways that mediate responses to metabolites like lactate, ketone bodies and fatty acids are less well characterized. Many metabolic sensing neurons also respond to insulin and leptin and other peripheral hormones and receive neural inputs from peripheral organs. Each set of afferent signals arrives with different temporal profiles and by different routes and these inputs are summated at the level of the membrane potential to produce a given neural firing pattern. In some obese individuals, the relative sensitivity of metabolic sensing neurons to various peripheral inputs is genetically reduced. This may provide one mechanism underlying their propensity to become obese when exposed to diets high in fat and caloric density. Thus, metabolic sensing neurons may provide a potential therapeutic target for the treatment of obesity.
大脑与外周持续进行着对话；外周将其代谢需求告知大脑，大脑则通过控制参与能量摄入、消耗和储存的躯体运动、自主神经及神经体液途径来满足这些需求。代谢感应神经元整合来自外周的各种代谢、体液和神经输入。这类神经元最初被称为“葡萄糖感应神经元”，它们也对外周的脂肪酸、激素和代谢物产生反应。它们整合于参与能量稳态调节的神经通路中。与大多数神经元不同，它们利用葡萄糖和其他代谢物作为信号分子来调节其膜电位和放电频率。对于葡萄糖感应神经元而言，葡萄糖激酶在葡萄糖感应过程中起限速作用，而介导对乳酸、酮体和脂肪酸等代谢物反应的途径则尚未得到充分表征。许多代谢感应神经元也对胰岛素、瘦素及其他外周激素产生反应，并接收来自外周器官的神经输入。每组传入信号以不同的时间模式、通过不同的途径到达，这些输入在膜电位水平进行总和，以产生特定的神经放电模式。在一些肥胖个体中，代谢感应神经元对各种外周输入的相对敏感性在基因层面降低。这可能是他们在摄入高脂肪和高热量饮食时容易肥胖的一种潜在机制。因此，代谢感应神经元可能为肥胖治疗提供一个潜在的治疗靶点。
