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首页> 外文期刊>Reviews in Endocrine & Metabolic Disorders >The ghrelin/GOAT/GHS-R system and energy metabolism
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The ghrelin/GOAT/GHS-R system and energy metabolism

机译：ghrelin / GOAT / GHS-R系统与能量代谢

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摘要

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.
机译：Ghrelin是一种脑肠肽，是通过反向药理学发现的，首先从猪胃提取物中分离得到。 Ghrelin与生长激素促分泌素受体（GHS-R）结合，并被Ghrelin O-酰基转移酶（GOAT）酰化在其丝氨酸3残基上。 ghrelin的几个重要生物学功能已得到确认，包括其释放生长激素和诱导食欲的作用。 Ghrelin主要通过激活GHS-R作用于下丘脑弓状核而发挥其中枢成因作用。周围生长素释放肽具有多种代谢作用，包括促进糖异生和脂肪沉积。这些影响以及食物摄入量的增加导致整体体重增加。 AMP激活的蛋白激酶是能量稳态中的关键酶，已被证明可调节ghrelin的中枢和外周代谢作用。下丘脑脂肪酸途径，下丘脑线粒体呼吸和解偶联蛋白2均已被证明是AMPK介导ghrelin致癌作用的下游靶标。生长激素释放肽的异常水平与几种代谢状况有关，例如肥胖，2型糖尿病，普拉德-威利综合症和神经性厌食症。 ghrelin / GOAT / GHS-R系统现已被视为开发抗肥胖症治疗的潜在目标。

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