Oncological Palliative Medicine, Division Oncology, Dept. Internal Medicine and Palliative Center, Dept. Interdisciplinary Medical Services, Cantonal Hospital, St.Gallen, Switzerland.
Curr Pharm Des. 2012;18(31):4800-12. doi: 10.2174/138161212803216870.
Ghrelin as a human natural hormone is involved in fundamental regulatory processes of eating and energy balance. Ghrelin signals the nutrient availability from the gastrointestinal tract to the central nervous system, up-regulates food intake and lowers energy expenditure mainly through hypothalamic mediators acting both centrally and peripherally including the gastrointestinal tract (motility, epithelium), promotes both neuro-endocrine and inflammatory signals to increase skeletal muscle growth and decrease protein breakdown, and increases lipolysis while body fat utilization is reduced. Ghrelin does more to exert its probably sentinel role around "human energy": it influences through mainly extra-hypothalamic actions the hedonic and incentive value of food, mood and anxiety, sleep-wake regulation, learning and memory, and neurogenesis. Recently numerous ghrelin gene-derived peptides were discovered, demonstrating the complexity within the ghrelin/ghrelin receptor axis. For clinical applications, not only the natural ghrelin and its slice variants, but also several modified or artificial molecules acting at ghrelin-associated receptors were and are developed. Current clinical applications are limited to clinical studies, focusing mainly on cachexia in chronic heart failure, COPD, cancer, endstage- renal-disease or cystic fibrosis, but also on frailty in elderly, gastrointestinal motility (e.g., gastroparesis, functional dyspepsia, postoperative ileus), after curative gastrectomy, anorexia nervosa, growth hormone deficient patients, alcohol craving, sleep-wake regulation (e.g. major depression), or sympathetic nervous activity in obesity. The results of completed, preliminary studies support the clinical potential of ghrelin, ghrelin gene-derived peptides, and artificial analogues, suggesting that larger clinical trials are demanded to move ghrelin towards an available and reimbursed pharmaceutical intervention.
胃饥饿素作为一种人类天然激素，参与进食和能量平衡的基本调节过程。胃饥饿素将来自胃肠道的营养可用性信号传递到中枢神经系统，通过作用于中枢和外周的下丘脑介质（包括胃肠道（运动、上皮））增加食物摄入并降低能量消耗，促进神经内分泌和炎症信号增加骨骼肌生长并减少蛋白质分解，增加脂肪分解，同时减少体脂利用。胃饥饿素在“人类能量”周围发挥其可能的哨兵作用：它主要通过额外的下丘脑作用影响食物的享乐和激励价值、情绪和焦虑、睡眠-觉醒调节、学习和记忆以及神经发生。最近发现了许多胃饥饿素基因衍生肽，证明了胃饥饿素/胃饥饿素受体轴内的复杂性。对于临床应用，不仅是天然胃饥饿素及其片段变体，还有几种作用于胃饥饿素相关受体的修饰或人工分子也在被开发和应用。目前的临床应用仅限于临床研究，主要集中在慢性心力衰竭、COPD、癌症、终末期肾病或囊性纤维化中的恶病质、老年虚弱、胃肠道动力（例如胃轻瘫、功能性消化不良、术后肠梗阻）、根治性胃切除术后、神经性厌食症、生长激素缺乏症患者、酒精渴望、睡眠-觉醒调节（例如重度抑郁症）或肥胖症中的交感神经活动。已完成的初步研究结果支持胃饥饿素、胃饥饿素基因衍生肽和人工类似物的临床潜力，表明需要更大规模的临床试验将胃饥饿素推向可用和报销的药物干预。
