Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, UK.
Rev Endocr Metab Disord. 2011 Sep;12(3):173-86. doi: 10.1007/s11154-011-9169-1.
Ghrelin is a brain-gut peptide that was discovered through reverse pharmacology and was first isolated from extracts of porcine stomach. Ghrelin binds to growth hormone secretagogue receptor (GHS-R) and is acylated on its serine 3 residue by ghrelin O-acyltransferase (GOAT). Several important biological functions of ghrelin have been identified, which include its growth hormone-releasing and appetite-inducing effects. Ghrelin exerts its central orexigenic effect mainly by acting on the hypothalamic arcuate nucleus via the activation of the GHS-R. Peripherally ghrelin has multiple metabolic effects which include promoting gluconeogenesis and fat deposition. These effects together with the increased food intake lead to an overall body weight gain. AMP-activated protein kinase, which is a key enzyme in energy homeostasis, has been shown to mediate the central and peripheral metabolic effects of ghrelin. The hypothalamic fatty acid pathway, hypothalamic mitochondrial respiration and uncoupling protein 2 have all been shown to act as the downstream targets of AMPK in mediating the orexigenic effects of ghrelin. Abnormal levels of ghrelin are associated with several metabolic conditions such as obesity, type 2 diabetes, Prader-Willi syndrome and anorexia nervosa. The ghrelin/GOAT/GHS-R system is now recognised as a potential target for the development of anti-obesity treatment.
胃饥饿素是一种脑肠肽，最初是通过反向药理学发现的，最初从猪胃提取物中分离出来。胃饥饿素与生长激素促分泌素受体（GHS-R）结合，并在其丝氨酸 3 残基上被胃饥饿素 O-酰基转移酶（GOAT）酰化。已经确定了胃饥饿素的几个重要生物学功能，包括其促进生长激素释放和食欲的作用。胃饥饿素通过激活 GHS-R 主要作用于下丘脑弓状核来发挥其中枢食欲刺激作用。外周胃饥饿素有多种代谢作用，包括促进糖异生和脂肪沉积。这些作用以及增加的食物摄入导致总体体重增加。AMP 激活蛋白激酶是能量稳态的关键酶，已被证明介导胃饥饿素的中枢和外周代谢作用。已经表明，下丘脑脂肪酸途径、下丘脑线粒体呼吸和解偶联蛋白 2 作为 AMPK 介导胃饥饿素食欲刺激作用的下游靶点。异常水平的胃饥饿素与几种代谢状况有关，如肥胖、2 型糖尿病、普拉德-威利综合征和神经性厌食症。胃饥饿素/GOAT/GHS-R 系统现在被认为是开发抗肥胖治疗的潜在靶点。
