Hallschmid Manfred, Benedict Christian, Born Jan, Fehm Horst-Lorenz, Kern Werner
Institute of Neuroendocrinology, University of Lübeck, Ratzeburger Allee 160, Haus 23a, 23538 Lübeck, Germany.
Physiol Behav. 2004 Oct 30;83(1):55-64. doi: 10.1016/j.physbeh.2004.07.023.
Maintaining a stable body weight set-point is assumed to rely on a homeostatic central nervous system (CNS) regulation of body fat with the particular involvement of hypothalamic pathways. The peripheral adiposity signals insulin and leptin convey information on the amount of energy stored as body fat to the arcuate nucleus of the hypothalamus, where anabolic/orexigenic and catabolic/anorexigenic pathways interact to regulate food intake and energy expenditure. One of the most prominent orexigenic messengers is neuropeptide Y (NPY), whereas melanocortins, including alpha-melanocyte-stimulating hormone (alpha-MSH), are essential for inducing anorexigenic effects. The melanocortin receptor 4 (MC4-R) plays the most important role in mediating catabolic effects of alpha-MSH. In this review, we present a series of own studies on NPY, insulin and MSH/ACTH4-10, an MC4-R agonist. The studies were all based on the intranasal route of administration which enables a direct access of the peptides to hypothalamic functions. NPY acutely attenuated electrocortical signs of meal-related satiety. Prolonged intranasal administration of insulin as well as of MSH induced weight loss in healthy human subjects. However, overweight subjects did not lose body fat after MSH administration. The results corroborate in humans the significance of all three messengers for the central nervous regulation of adiposity and might contribute to the future development of medical strategies against body-weight-related disorders.
维持稳定的体重设定点被认为依赖于中枢神经系统（CNS）对体脂的稳态调节，特别是下丘脑通路的参与。外周肥胖信号胰岛素和瘦素将作为体脂储存的能量量信息传递到下丘脑的弓状核，在那里合成代谢/促食欲和分解代谢/抑食欲通路相互作用以调节食物摄入和能量消耗。最突出的促食欲信使之一是神经肽Y（NPY），而包括α-黑素细胞刺激激素（α-MSH）在内的黑皮质素对于诱导抑食欲作用至关重要。黑皮质素受体4（MC4-R）在介导α-MSH的分解代谢作用中起最重要作用。在本综述中，我们展示了一系列关于NPY、胰岛素和MSH/ACTH4-10（一种MC4-R激动剂）的自身研究。这些研究均基于鼻内给药途径，该途径使肽能够直接作用于下丘脑功能。NPY急性减弱了与进餐相关的饱腹感的脑电信号。在健康人类受试者中，长期鼻内给予胰岛素以及MSH可导致体重减轻。然而，超重受试者在给予MSH后并未减少体脂。这些结果在人类中证实了这三种信使对于肥胖的中枢神经调节的重要性，并可能有助于未来针对体重相关疾病的医学策略的发展。
