Thomas Alanna S, Sassi Martina, Angelini Roberto, Morgan Alwena H, Davies Jeffrey S
Molecular Neurobiology, Institute of Life Sciences, School of Medicine, Swansea University, Swansea, United Kingdom.
Front Physiol. 2022 Jun 30;13:831641. doi: 10.3389/fphys.2022.831641. eCollection 2022.
Acyl-ghrelin (AG) is an orexigenic hormone that has a unique octanoyl modification on its third serine residue. It is often referred to as the "hunger hormone" due to its involvement in stimulating food intake and regulating energy homeostasis. The discovery of the enzyme ghrelin-O-acyltransferase (GOAT), which catalyses ghrelin acylation, provided further insights into the relevance of this lipidation process for the activation of the growth hormone secretagogue receptor (GHS-R) by acyl-ghrelin. Although acyl-ghrelin is predominantly linked with octanoic acid, a range of saturated fatty acids can also bind to ghrelin possibly leading to specific functions. Sources of ghrelin acylation include beta-oxidation of longer chain fatty acids, with contributions from fatty acid synthesis, the diet, and the microbiome. In addition, both acyl-ghrelin and unacyl-ghrelin (UAG) have feedback effects on lipid metabolism which in turn modulate their levels. Recently we showed that whilst acyl-ghrelin promotes adult hippocampal neurogenesis and enhances memory function, UAG inhibits these processes. As a result, we postulated that the circulating acyl-ghrelin:unacyl-ghrelin (AG:UAG) ratio might be an important regulator of neurogenesis and cognition. In this review, we discuss emerging evidence behind the relevance of ghrelin acylation in the context of brain physiology and pathology, as well as the current challenges of identifying the provenance of the acyl moiety.
酰基胃饥饿素（AG）是一种促食欲激素，其第三个丝氨酸残基上有独特的辛酰基修饰。由于它参与刺激食物摄入和调节能量平衡，常被称为“饥饿激素”。催化胃饥饿素酰化的胃饥饿素-O-酰基转移酶（GOAT）的发现，进一步揭示了这种脂化过程与酰基胃饥饿素激活生长激素促分泌素受体（GHS-R）的相关性。尽管酰基胃饥饿素主要与辛酸相连，但一系列饱和脂肪酸也能与胃饥饿素结合，可能导致特定功能。胃饥饿素酰化的来源包括长链脂肪酸的β-氧化，脂肪酸合成、饮食和微生物群也有贡献。此外，酰基胃饥饿素和去酰基胃饥饿素（UAG）对脂质代谢都有反馈作用，进而调节它们的水平。最近我们发现，酰基胃饥饿素促进成年海马神经发生并增强记忆功能，而去酰基胃饥饿素则抑制这些过程。因此，我们推测循环中的酰基胃饥饿素：去酰基胃饥饿素（AG：UAG）比值可能是神经发生和认知的重要调节因子。在这篇综述中，我们讨论了胃饥饿素酰化在脑生理学和病理学背景下相关性的新证据，以及确定酰基部分来源的当前挑战。
