Smith Pauline M, Ferguson Alastair V
Dept. of Biomedical and Molecular Sciences, Queen's University, Kingston ON, Canada, K7L 3N6.
Curr Pharm Des. 2014;20(9):1392-9. doi: 10.2174/13816128113199990560.
In order to maintain an ideal body weight, an organism must balance energy intake with energy expenditure. It is well known that metabolic signals derived in the periphery act in well-defined hypothalamic and brainstem neuronal circuits to control energy homeostasis. As such, peripheral signals that convey information regarding nutritional and metabolic status of the individual must be able to access and control these neuronal circuits in order to direct both food intake and energy expenditure. Within the hypothalamus, the arcuate nucleus of the hypothalamus has become recognized as a critical center in this integrated circuitry. Although there is considerable anatomical evidence indicating that the arcuate is protected by the blood brain barrier, neurons in this region have been repeatedly suggested to directly sense many circulating signals which do not readily diffuse across this barrier. In this review we will describe the hypothalamic circuitry involved in the regulation of energy homeostasis and will discuss data indicating that the arcuate nucleus is, in fact, protected by the blood brain barrier. We will then consider alternative mechanisms through which one specific circulating adipokine, leptin, can gain access to and influence central nervous sites involved in the regulation of energy homeostasis without the requirement for direct access from the peripheral circulation to arcuate neurons.
为了维持理想体重，生物体必须使能量摄入与能量消耗保持平衡。众所周知，源自外周的代谢信号作用于明确的下丘脑和脑干神经回路，以控制能量平衡。因此，传达个体营养和代谢状态信息的外周信号必须能够进入并控制这些神经回路，从而指导食物摄入和能量消耗。在下丘脑中，下丘脑弓状核已被公认为这一整合神经回路中的关键中枢。尽管有大量解剖学证据表明弓状核受到血脑屏障的保护，但该区域的神经元多次被认为可直接感知许多不易透过该屏障扩散的循环信号。在本综述中，我们将描述参与能量平衡调节的下丘脑神经回路，并讨论表明弓状核实际上受到血脑屏障保护的数据。然后，我们将考虑一种特定循环脂肪因子——瘦素——能够进入并影响参与能量平衡调节的中枢神经部位的替代机制，而无需从外周循环直接进入弓状核神经元。
