Stomach regulates energy balance via acylated ghrelin and desacyl ghrelin.
OBJECTIVE
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.
Asakawa
A
A
Division of Diabetes, Digestive and Kidney Diseases, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
Inui
A
A
Fujimiya
M
M
Sakamaki
R
R
Shinfuku
N
N
Ueta
Y
Y
Meguid
M M
MM
Kasuga
M
M
D000107:Acetylation; D000818:Animals; D001831:Body Temperature / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D018076:DNA, Complementary / Q000235:genetics; D004435:Eating / Q000187:drug effects / Q000502:physiology; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology; D005753:Gastric Mucosa / Q000378:metabolism*; D054439:Ghrelin; D007031:Hypothalamus / Q000502:physiology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D036361:Peptide Hormones / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D018076:DNA, Complementary; D054439:Ghrelin; D036361:Peptide Hormones; D016760:Proto-Oncogene Proteins c-fos; C422650:ghrelin, des-n-octanoyl