RT Journal Article
SR Electronic
T1 Stomach regulates energy balance via acylated ghrelin and desacyl ghrelin
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 18
OP 24
DO 10.1136/gut.2004.038737
VO 54
IS 1
A1 A Asakawa
A1 A Inui
A1 M Fujimiya
A1 R Sakamaki
A1 N Shinfuku
A1 Y Ueta
A1 M M Meguid
A1 M Kasuga
YR 2005
UL http://gut.bmj.com/content/54/1/18.abstract
AB 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.