Obesity Research Centre, Department of Internal Medicine, University of Cincinnati College of Medicine, 2170 E. Galbraith Rd., Cincinnati, OH 45237, USA.
Am J Physiol Endocrinol Metab. 2010 May;298(5):E909-19. doi: 10.1152/ajpendo.00191.2009. Epub 2010 Feb 23.
Effective control of body weight and energy homeostasis requires stringent regulation of caloric intake and energy expenditure. Gut-brain interactions comprise a central axis for the control of energy homeostasis by integrating the intake of nutrients with an effective utilization of ingested calories either by storage or by expenditure as cellular fuel. Ghrelin, a stomach-derived peptide, is the only known circulating orexigenic hormone. It is acylated with a medium-chain fatty acid by the enzyme ghrelin O-acetyltransferase (GOAT) and displays a broad range of activity, from central control of food intake to peripheral functions such as gastric emptying and insulin secretion. PYY, a peptide produced by L cells of the small intestine and rectum, has been shown to inhibit gut motility and is proposed to stimulate a powerful central satiety response. In recent years, pharmacological studies in animals and clinical studies in humans have contributed to our knowledge of principal ghrelin and PYY actions. However, valuable findings from studies using ghrelin-deficient mice, ghrelin receptor [growth hormone secretagogue receptor-1a (GHSR1a)]-deficient mice, double-knockout mice (for ghrelin and GHSR), and GOAT-deficient or -overexpressor mice, as well as mice deficient for PYY or neuropeptide Y receptors have allowed better definition of the actual physiological functions of ghrelin and PYY. This review summarizes findings from mutant mouse studies with emphasis on respective gene knockout and transgenic animals and describes how these studies contribute to the current understanding of how endogenous ghrelin and PYY as two major representatives of endocrine gut-brain communications may regulate energy and glucose homeostasis.
有效控制体重和能量平衡需要严格调节热量摄入和能量消耗。肠-脑相互作用构成了控制能量平衡的中心轴，通过将营养物质的摄入与有效利用摄入的卡路里（通过储存或作为细胞燃料消耗）相结合来调节能量平衡。胃饥饿素是一种源自胃的肽，是唯一已知的循环食欲激素。它被胃饥饿素 O-乙酰基转移酶（GOAT）酰化为中链脂肪酸，具有广泛的活性，从对食物摄入的中枢控制到外周功能，如胃排空和胰岛素分泌。PYY 是一种由小肠和直肠的 L 细胞产生的肽，已被证明能抑制肠道蠕动，并被提议刺激强烈的中枢饱腹感反应。近年来，动物的药理学研究和人类的临床研究为我们了解主要的胃饥饿素和 PYY 作用做出了贡献。然而，使用胃饥饿素缺乏小鼠、胃饥饿素受体[生长激素促分泌素受体-1a（GHSR1a）]缺乏小鼠、双敲除小鼠（用于胃饥饿素和 GHSR）、GOAT 缺乏或过表达小鼠以及 PYY 或神经肽 Y 受体缺乏小鼠进行的研究提供了有价值的发现，这些研究使胃饥饿素和 PYY 的实际生理功能得到了更好的定义。这篇综述总结了突变体小鼠研究的结果，重点介绍了各自的基因敲除和转基因动物，并描述了这些研究如何有助于当前对作为内分泌肠-脑通讯两个主要代表的内源性胃饥饿素和 PYY 如何调节能量和葡萄糖平衡的理解。
