Stomach regulates energy balance via acylated ghrelin and desacyl ghrelin
Stomach regulates energy balance via acylated ghrelin and desacyl ghrelin
复制标题
DOI：
10.1136/gut.2004.038737
复制
发表时间：
2005-01-01
期刊：
影响因子：
24.5
通讯作者：
Kasuga, M
中科院分区：
文献类型：
--
作者：
Asakawa, A;Inui, A;Kasuga, M
背景/目的：胃肽生长素释放肽是生长激素促分泌素受体的内源性配体，具有两种主要分子形式：酰化生长素释放肽和去酰基生长素释放肽。酰化生长素释放肽可诱导正能量平衡，而去酰基生长素释放肽据报道没有任何内分泌活性。作者研究了去酰基生长素释放肽对能量平衡的影响。方法：作者测量了给予去酰基生长素释放肽后小鼠的食物摄入量、胃排空、下丘脑中的 c-Fos 表达以及下丘脑神经肽的基因表达。为了探索去酰基生长素释放肽长期过度表达的影响，创建了过度表达去酰基生长素释放肽的转基因小鼠。结果：给予去酰基生长素释放肽通过作用于下丘脑的室旁核和弓状核，减少食物摄入和胃排空率。去酰基生长素释放肽增加了下丘脑中抑制食欲的可卡因和安非他明调节的转录物和尿皮质素的基因表达。去酰基生长素释放肽过度表达的小鼠表现出体重、食物摄入量和脂肪垫质量的下降，并伴有线性生长的适度下降。去酰基生长素释放肽过表达小鼠的胃排空也减少。结论：这些发现表明，与酰化生长素释放肽相比，去酰基生长素释放肽通过减少食物摄入和延迟胃排空而诱导负能量平衡。该作用是通过下丘脑介导的。尽管源自相同的前体，但这两种肽的相反作用表明胃可能作为内分泌器官参与能量平衡的调节。
Background/Aims: The gastric peptide ghrelin, an endogenous ligand for growth-hormone secretagogue receptor, has two major molecular forms: acylated ghrelin and desacyl ghrelin. Acylated ghrelin induces a positive energy balance, while desacyl ghrelin has been reported to be devoid of any endocrine activities. The authors examined the effects of desacyl ghrelin on energy balance.Methods: The authors measured food intake, gastric emptying, c-Fos expression in the hypothalamus, and gene expression of hypothalamic neuropeptides in mice after administration of desacyl ghrelin. To explore the effects of long term overexpression of desacyl ghrelin, transgenic mice that overexpressed desacyl ghrelin were created.Results: Administration of desacyl ghrelin decreased food intake and gastric emptying rate through an action on the paraventricular nucleus and the arcuate nucleus in the hypothalamus. Gene expression of anorexigenic cocaine and amphetamine regulated transcript and urocortin in the hypothalamus was increased by desacyl ghrelin. Desacyl ghrelin overexpressing mice exhibited a decrease in body weight, food intake, and fat pad mass weight accompanied by moderately decreased linear growth. Gastric emptying was also decreased in desacyl ghrelin overexpressing mice.Conclusions: These findings indicate that in contrast to acylated ghrelin, desacyl ghrelin induces a negative energy balance by decreasing food intake and delaying gastric emptying. The effect is mediated via the hypothalamus. Although derived from the same precursor, the inverse effects of these two peptides suggest that the stomach might be involved as an endocrine organ in the regulation of the energy balance.