Gortan Cappellari Gianluca, Barazzoni Rocco
Department of Medical, Surgical and Health Sciences, University of Trieste, Strada di Fiume, 447, 34149, Trieste, Italy.
Azienda Sanitaria Universitaria Integrata di Trieste (ASUITS), Trieste, Italy.
Eat Weight Disord. 2019 Dec;24(6):997-1013. doi: 10.1007/s40519-018-0599-6. Epub 2018 Oct 24.
Ghrelin is a gastric hormone circulating in acylated (AG) and unacylated (UnAG) forms. This narrative review aims at presenting current emerging knowledge on the impact of ghrelin forms on energy balance and metabolism. AG represents ~ 10% of total plasma ghrelin, has an appetite-stimulating effect and is the only form for which a receptor has been identified. Moreover, other metabolic AG-induced effects have been reported, including the modulation of glucose homeostasis with stimulation of liver gluconeogenesis, the increase of fat mass and the improvement of skeletal muscle mitochondrial function. On the other hand, UnAG has no orexigenic effects, however recent reports have shown that it is directly involved in the modulation of skeletal muscle energy metabolism by improving a cluster of interlinked functions including mitochondrial redox activities, tissue inflammation and insulin signalling and action. These findings are in agreement with human studies which show that UnAG circulating levels are positively associated with insulin sensitivity both in metabolic syndrome patients and in a large cohort from the general population. Moreover, ghrelin acylation is regulated by a nutrient sensor mechanism, specifically set on fatty acids availability. These recent findings consistently point towards a novel independent role of UnAG as a regulator of muscle metabolic pathways maintaining energy status and tissue anabolism. While a specific receptor for UnAG still needs to be identified, recent evidence strongly supports the hypothesis that the modulation of ghrelin-related molecular pathways, including those involved in its acylation, may be a potential novel target in the treatment of metabolic derangements in disease states characterized by metabolic and nutritional complications.Level of evidence Level V, narrative review.
胃饥饿素是一种以酰化（AG）和去酰化（UnAG）形式循环的胃激素。本叙述性综述旨在介绍关于胃饥饿素形式对能量平衡和代谢影响的当前新出现的知识。AG占血浆总胃饥饿素的约10%，具有刺激食欲的作用，并且是唯一已鉴定出受体的形式。此外，还报道了其他由AG诱导的代谢作用，包括通过刺激肝脏糖异生调节葡萄糖稳态、增加脂肪量以及改善骨骼肌线粒体功能。另一方面，UnAG没有促食欲作用，然而最近的报道表明，它通过改善包括线粒体氧化还原活性、组织炎症和胰岛素信号传导及作用在内的一系列相互关联的功能，直接参与骨骼肌能量代谢的调节。这些发现与人体研究一致，人体研究表明，在代谢综合征患者和来自普通人群的大型队列中，UnAG循环水平均与胰岛素敏感性呈正相关。此外，胃饥饿素的酰化受一种营养传感器机制调节，该机制特别取决于脂肪酸的可用性。这些最新发现一致指向UnAG作为维持能量状态和组织合成代谢的肌肉代谢途径调节剂的新的独立作用。虽然仍需要鉴定UnAG的特异性受体，但最近的证据有力地支持了这样一种假说，即调节与胃饥饿素相关的分子途径，包括那些参与其酰化的途径，可能是治疗以代谢和营养并发症为特征的疾病状态下代谢紊乱的潜在新靶点。证据级别：V级，叙述性综述。
