Ghrelin is an appetite-stimulatory signal from stomach with structural resemblance to motilin

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 120; no. 2; pp. 337 - 345
• Main Authors: Asakawa, Akihiro, Inui, Akio, Kaga, Oshihiro, Yuzuriha, Hideki, Nagata, Toshiaki, Ueno, Naohiko, Makino, Susumu, Fujimiya, Mineko, Niijima, Akira, Fujino, Masayuki A., Kasuga, Masato
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-02-2001; Elsevier
• Subjects: Amino Acid Sequence; Animals; Appetite - physiology; Biological and medical sciences; Blotting, Northern; Digestive system; Electrophysiology; Energy Metabolism - drug effects; Energy Metabolism - physiology; Feeding Behavior - drug effects; Feeding Behavior - physiology; Gastric Emptying - drug effects; Gastric Emptying - physiology; Gene Expression - physiology; Ghrelin; Hypothalamus - physiology; Injections, Intraventricular; Interleukin-1 - pharmacology; Investigative techniques, diagnostic techniques (general aspects); Male; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Obese; Molecular Sequence Data; Motilin - chemistry; Motilin - genetics; Neuropeptide Y - genetics; Oxygen Consumption - drug effects; Oxygen Consumption - physiology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Peptide Hormones; Peptides - chemistry; Peptides - genetics; Peptides - pharmacology; Rats; Rats, Wistar; Receptors, Gastrointestinal Hormone - genetics; Receptors, Neuropeptide - genetics; RNA, Messenger - analysis; Stomach - innervation; Stomach - physiology; Vagus Nerve - drug effects; Vagus Nerve - physiology; AGRP; IL; MCH; GHS-R; ICV; Stomach; Obesity; Rat; Peptide hormone; Rodentia; Nutrition disorder; Somatotropin hormone; Activity; Receiver; Appetite stimulant; Motiline; Vertebrata; Gastrointestinal hormone; Mammalia; Food intake; Animal; Leptin; Biological effect; Vagus nerve; Nutritional status; Comparative study
• ISSN: 0016-5085; 1528-0012
• DOI: 10.1053/gast.2001.22158

Background & Aims: Ghrelin, an endogenous ligand for growth hormone secretagogue receptor, was recently identified in the rat stomach. We examined the effects of the gastric peptide ghrelin on energy balance in association with leptin and vagal nerve activity. Methods: Food intake, oxygen consumption, gastric emptying, and hypothalamic neuropeptide Y (NPY) messenger RNA expression were measured after intra-third cerebroventricular or intraperitoneal injections of ghrelin in mice. The gastric vagal nerve activity was recorded after intravenous administration in rats. Gastric ghrelin gene expression was assessed by Northern blot analysis. Repeated coadministration of ghrelin and interleukin (IL)-1β was continued for 5 days. Results: Ghrelin exhibited gastroprokinetic activity with structural resemblance to motilin and potent orexigenic activity through action on the hypothalamic neuropeptide Y (NPY) and Y1 receptor, which was lost after vagotomy. Ghrelin decreased gastric vagal afferent discharge in contrast to other anorexigenic peptides that increased the activity. Ghrelin gene expression in the stomach was increased by fasting and in ob/ob mice, and was decreased by administration of leptin and IL-1β. Peripherally administered ghrelin blocked IL-1β–induced anorexia and produced positive energy balance by promoting food intake and decreasing energy expenditure. Conclusions: Ghrelin, which is negatively regulated by leptin and IL-1β, is secreted by the stomach and increases arcuate NPY expression, which in turn acts through Y1 receptors to increase food intake and decrease energy expenditure. Gastric peptide ghrelin may thus function as part of the orexigenic pathway downstream from leptin and is a potential therapeutic target not only for obesity but also for anorexia and cachexia.
GASTROENTEROLOGY 2001;120:337-345