Asakawa A, Inui A, Kaga T, Yuzuriha H, Nagata T, Ueno N, Makino S, Fujimiya M, Niijima A, Fujino M A, Kasuga M
Second Department of Internal Medicine, Kobe University School of Medicine, Kobe, Japan.
Gastroenterology. 2001 Feb;120(2):337-45. doi: 10.1053/gast.2001.22158.
BACKGROUND & AIMS: : Ghrelin, an endogenous ligand for growth hormone secretagogue receptor, was recently identified in the rat stomach. We examined the effects of the gastric peptide ghrelin on energy balance in association with leptin and vagal nerve activity.
: Food intake, oxygen consumption, gastric emptying, and hypothalamic neuropeptide Y (NPY) messenger RNA expression were measured after intra-third cerebroventricular or intraperitoneal injections of ghrelin in mice. The gastric vagal nerve activity was recorded after intravenous administration in rats. Gastric ghrelin gene expression was assessed by Northern blot analysis. Repeated coadministration of ghrelin and interleukin (IL)-1 beta was continued for 5 days.
: Ghrelin exhibited gastroprokinetic activity with structural resemblance to motilin and potent orexigenic activity through action on the hypothalamic neuropeptide Y (NPY) and Y(1) receptor, which was lost after vagotomy. Ghrelin decreased gastric vagal afferent discharge in contrast to other anorexigenic peptides that increased the activity. Ghrelin gene expression in the stomach was increased by fasting and in ob/ob mice, and was decreased by administration of leptin and IL-1 beta. Peripherally administered ghrelin blocked IL-1 beta-induced anorexia and produced positive energy balance by promoting food intake and decreasing energy expenditure.
: Ghrelin, which is negatively regulated by leptin and IL-1 beta, is secreted by the stomach and increases arcuate NPY expression, which in turn acts through Y(1) receptors to increase food intake and decrease energy expenditure. Gastric peptide ghrelin may thus function as part of the orexigenic pathway downstream from leptin and is a potential therapeutic target not only for obesity but also for anorexia and cachexia.
生长激素促分泌素受体的内源性配体胃饥饿素最近在大鼠胃中被发现。我们研究了胃肽胃饥饿素与瘦素和迷走神经活动相关的能量平衡效应。
在小鼠第三脑室或腹腔注射胃饥饿素后，测量食物摄入量、耗氧量、胃排空及下丘脑神经肽Y（NPY）信使核糖核酸表达。在大鼠静脉给药后记录胃迷走神经活动。通过Northern印迹分析评估胃饥饿素基因表达。胃饥饿素和白细胞介素（IL）-1β重复联合给药持续5天。
胃饥饿素表现出与胃动素结构相似的促胃动力活性，通过作用于下丘脑神经肽Y（NPY）和Y（1）受体具有强大的促食欲活性，迷走神经切断后该活性丧失。与其他增加活性的厌食肽相反，胃饥饿素降低胃迷走神经传入放电。禁食和ob/ob小鼠胃中胃饥饿素基因表达增加，而给予瘦素和IL-1β后表达降低。外周给予胃饥饿素可阻断IL-1β诱导的厌食，并通过促进食物摄入和减少能量消耗产生正能量平衡。
胃饥饿素由胃分泌，受瘦素和IL-1β负调控，增加弓状核NPY表达，进而通过Y（1）受体增加食物摄入和减少能量消耗。因此，胃肽胃饥饿素可能作为瘦素下游促食欲途径的一部分发挥作用，不仅是肥胖的潜在治疗靶点，也是厌食和恶病质的潜在治疗靶点。
