Cummings David E
Department of Medicine, Division of Metabolism, Endocrinology and Nutrition, University of Washington, VA Puget Sound Health Care System, 1660 South Columbian Way, S-111-Endo, Seattle, WA 98108, USA.
Physiol Behav. 2006 Aug 30;89(1):71-84. doi: 10.1016/j.physbeh.2006.05.022. Epub 2006 Jul 21.
Ghrelin, an acylated upper gastrointestinal peptide, is the only known orexigenic hormone. Considerable evidence implicates ghrelin in mealtime hunger and meal initiation. Circulating levels decrease with feeding and increase before meals, achieving concentrations sufficient to stimulate hunger and food intake. Preprandial ghrelin surges occur before every meal on various fixed feeding schedules and also among individuals initiating meals voluntarily without time- or food-related cues. Ghrelin injections stimulate food intake rapidly and transiently, primarily by increasing appetitive feeding behaviors and the number of meals. Preprandial ghrelin surges are probably triggered by sympathetic nervous output. Postprandial suppression is not mediated by nutrients in the stomach or duodenum, where most ghrelin is produced. Rather, it results from post-ingestive increases in lower intestinal osmolarity (information probably relayed to the foregut via enteric nervous signaling), as well as from insulin surges. Consequently, ingested lipids suppress ghrelin poorly compared with other macronutrients. Beyond a probable role in meal initiation, ghrelin also fulfills established criteria for an adiposity-related hormone involved in long-term body-weight regulation. Ghrelin levels circulate in relation to energy stores and manifest compensatory changes in response to body-weight alterations. Ghrelin crosses the blood-brain barrier and stimulates food intake by acting on several classical body-weight regulatory centers, including the hypothalamus, hindbrain, and mesolimbic reward system. Chronic ghrelin administration increases body weight via diverse, concerted actions on food intake, energy expenditure, and fuel utilization. Congenital ablation of the ghrelin or ghrelin-receptor gene causes resistance to diet-induced obesity, and pharmacologic ghrelin blockade reduces food intake and body weight. Ghrelin levels are high in Prader-Willi syndrome and low after gastric bypass surgery, possibly contributing to body-weight alterations in these settings. Extant evidence favors roles for ghrelin in both short-term meal initiation and long-term energy homeostasis, making it an attractive target for drugs to treat obesity and/or wasting disorders.
胃饥饿素是一种酰化的上消化道肽，是唯一已知的促食欲激素。大量证据表明胃饥饿素与进餐时的饥饿感和开始进食有关。进食时循环水平下降，餐前升高，达到足以刺激饥饿感和食物摄入的浓度。在各种固定的进食时间表上，每餐之前都会出现餐前胃饥饿素激增，在没有时间或食物相关提示的情况下自愿开始进食的个体中也会出现。注射胃饥饿素会迅速且短暂地刺激食物摄入，主要是通过增加食欲性进食行为和进餐次数。餐前胃饥饿素激增可能是由交感神经输出触发的。餐后抑制不是由胃或十二指肠中的营养物质介导的，胃饥饿素大多在这些部位产生。相反，它是由摄入后下肠道渗透压升高（信息可能通过肠神经信号传递到前肠）以及胰岛素激增导致的。因此，与其他宏量营养素相比，摄入的脂质对胃饥饿素的抑制作用较弱。除了在开始进食中可能发挥的作用外，胃饥饿素还符合作为参与长期体重调节的肥胖相关激素的既定标准。胃饥饿素水平与能量储备相关循环，并在体重改变时表现出代偿性变化。胃饥饿素穿过血脑屏障，通过作用于几个经典的体重调节中心来刺激食物摄入，包括下丘脑、后脑和中脑边缘奖赏系统。长期给予胃饥饿素会通过对食物摄入、能量消耗和燃料利用的多种协同作用来增加体重。胃饥饿素或胃饥饿素受体基因的先天性缺失会导致对饮食诱导的肥胖产生抗性，而药物性胃饥饿素阻断会减少食物摄入和体重。普拉德-威利综合征患者的胃饥饿素水平较高，胃旁路手术后则较低，这可能导致这些情况下的体重改变。现有证据支持胃饥饿素在短期进餐启动和长期能量稳态中都发挥作用，使其成为治疗肥胖症和/或消瘦症药物的有吸引力的靶点。
