Popovic Vera, Duntas Leonidas H
Neuroendocrine Unit, Institute of Endocrinology, University Clinical Center, Belgrade, Serbia, Yugoslavia.
Nutr Neurosci. 2005 Feb;8(1):1-5. doi: 10.1080/10284150400027107.
Energy balance is largely regulated by the central nervous system (CNS), which senses metabolic status from a wide range of humoral and neural signals, and controls energy intake. Accumulating evidence supports the model that stimulation of leptin- and ghrelin-responsive pathways, including the central melanocortin system, in the hypothalamus, contributes to the maintenance of body weight. Ghrelin is the brain-gut peptide with growth hormone-releasing and appetite-inducing activities. It is mainly secreted from the stomach and acts as an afferent signal to the hypothalamus and hindbrain. Leptin, the adipocyte hormone, is believed to tonically act as an afferent signal from adipose tissue to the brain, in particular hypothalamus, as a part of negative feedback loop regulating the size of energy stores and energy balance. Dysregulation of these pathways is a marker of changes in energy balance. Ghrelin is negatively correlated with weight and obese subjects have lower ghrelin levels than lean subjects, consistent with a compensatory rather than causal role for ghrelin in obesity. On the contrary, circulating leptin levels correlate in proportion to adiposity being high in obesity suggesting that human obesity is associated with insensitivity to leptin. The leptin resistance in diet-induced obesity emphasizes that environmental factors can modulate leptin sensitivity. It is speculated that through hypothalamic/pituitary axis ghrelin and leptin operate as a metabolic switch. Ghrelin actually transfers information from the stomach to the hypothalamus in cooperation with leptin and provides calories that growth hormone (GH) needs for growth and repair. Pharmacological manipulations of circulating hormone levels may work well in "cheating" the brain regarding information from the periphery. It might also be necessary to combine two or three agents to fight obesity. A combination of drugs that decrease preprandial appetite (ghrelin antagonist) and increase post-prandial satiety (gut hormone fragment peptide YY 3-36) might have a chance of achieving sustained weight loss. The administration of exogenous satiety hormone peptide YY 3-36 (PYY) may prevent the action of appetite-stimulating hypothalamic circuits on the anorexigenic melanocortin pathways.
能量平衡主要由中枢神经系统（CNS）调节，中枢神经系统从广泛的体液和神经信号中感知代谢状态，并控制能量摄入。越来越多的证据支持这样一种模型，即刺激下丘脑包括中枢黑皮质素系统在内的瘦素和胃饥饿素反应途径，有助于维持体重。胃饥饿素是一种具有生长激素释放和诱导食欲活性的脑肠肽。它主要由胃分泌，并作为一种传入信号作用于下丘脑和后脑。瘦素是一种脂肪细胞激素，被认为作为负反馈回路的一部分，持续地作为从脂肪组织到大脑，特别是下丘脑的传入信号，调节能量储备的大小和能量平衡。这些途径的失调是能量平衡变化的一个标志。胃饥饿素与体重呈负相关，肥胖受试者的胃饥饿素水平低于瘦受试者，这表明胃饥饿素在肥胖中起补偿作用而非因果作用。相反，循环瘦素水平与肥胖程度成正比，肥胖时瘦素水平较高，这表明人类肥胖与对瘦素不敏感有关。饮食诱导肥胖中的瘦素抵抗强调环境因素可调节瘦素敏感性。据推测，胃饥饿素和瘦素通过下丘脑/垂体轴作为一种代谢开关发挥作用。实际上，胃饥饿素与瘦素协同作用，将信息从胃传递到下丘脑，并提供生长激素（GH）生长和修复所需的热量。对循环激素水平进行药理学操作可能有助于在欺骗大脑有关外周信息方面发挥良好作用。也可能有必要联合使用两三种药物来对抗肥胖。一种减少餐前食欲（胃饥饿素拮抗剂）并增加餐后饱腹感（肠激素片段肽YY 3-36）的药物组合可能有机会实现持续体重减轻。外源性饱腹感激素肽YY 3-36（PYY）的给药可能会阻止刺激食欲的下丘脑回路对厌食性黑皮质素途径的作用。
