STOMACH

Stomach regulates energy balance via acylated ghrelin and desacyl ghrelin

A Asakawa¹, A Inui¹, M Fujimiya², R Sakamaki³, N Shinfuku³, Y Ueta⁴, M M Meguid⁵, M Kasuga¹

¹ Division of Diabetes, Digestive and Kidney Diseases, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
² Department of Anatomy, Shiga University of Medical Science, Shiga, Japan
³ International Center for Medical Research, Kobe University Graduate School of Medicine, Kobe, Japan
⁴ Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
⁵ Department of Surgery, SUNY Upstate Medical University, Syracuse, NY, USA

Correspondence to:
Correspondence to:
Professor A Inui
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{at}med.kobe-u.ac.jp

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.

Abbreviations: ACSF, artificial cerebrospinal fluid; AGRP, agouti related protein; ARC, arcuate nucleus; CART, cocaine and amphetamine regulated transcript; CRF, corticotrophin releasing factor; FFA, free fatty acids; GHS-R, growth hormone secretagogue receptor; G3PDH, glyceraldehyde 3-phosphate dehydrogenase; ICV, intra-third cerebroventricular(ly); MCH, melanin concentrating hormone; NTS, nucleus tractus solitarius; NMU, neuromedin U; PBS, phosphate buffered saline; POMC, proopiomelanocortin; PVN, paraventricular nucleus; RT-PCR, reverse transcription polymerase chain reaction

Keywords: gastric peptide; hypothalamus; food intake; body weight; transgenic mice

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Acylated ghrelin stimulates food intake, but des-acylated ghrelin has no effect

Stephen R Bloom, et al.

Gut Online, 20 Jul 2005 [Full text]