Divisions of Hypothalamic Research and Endocrinology and Metabolism, Department of Medicine, The University of Texas Southwestern Medical Center Dallas, TX, USA ; Department of Psychiatry, The University of Texas Southwestern Medical Center Dallas, TX, USA.
Front Neurosci. 2013 Jul 16;7:121. doi: 10.3389/fnins.2013.00121. eCollection 2013.
Ghrelin is an octanoylated peptide hormone, produced by endocrine cells of the stomach, which acts in the brain to increase food intake and body weight. Our understanding of the mechanisms underlying ghrelin's effects on eating behaviors has been greatly improved by the generation and study of several genetically manipulated mouse models. These models include mice overexpressing ghrelin and also mice with genetic deletion of ghrelin, the ghrelin receptor [the growth hormone secretagogue receptor (GHSR)] or the enzyme that post-translationally modifies ghrelin [ghrelin O-acyltransferase (GOAT)]. In addition, a GHSR-null mouse model in which GHSR transcription is globally blocked but can be cell-specifically reactivated in a Cre recombinase-mediated fashion has been generated. Here, we summarize findings obtained with these genetically manipulated mice, with the aim to highlight the significance of the ghrelin system in the regulation of both homeostatic and hedonic eating, including that occurring in the setting of chronic psychosocial stress.
胃泌素是一种八酰化肽激素,由胃内分泌细胞产生,在大脑中发挥作用,增加食物摄入和体重。通过生成和研究几种基因操作的小鼠模型,我们对胃泌素对进食行为影响的机制有了更深入的了解。这些模型包括过度表达胃泌素的小鼠,以及胃泌素、胃泌素受体[生长激素促分泌素受体(GHSR)]或翻译后修饰胃泌素的酶[胃泌素 O-酰基转移酶(GOAT)]基因缺失的小鼠。此外,还生成了一种 GHSR 基因敲除小鼠模型,该模型中 GHSR 转录被全局阻断,但可通过 Cre 重组酶介导的方式在细胞特异性水平上重新激活。在这里,我们总结了这些基因操作小鼠模型的研究结果,旨在强调胃泌素系统在调节稳态和享乐性进食中的重要性,包括在慢性心理社会应激环境下的进食。