This Article Full Text Full Text (PDF) All Versions of this Article: 147/5/2306    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Toshinai, K. Articles by Nakazato, M. Search for Related Content PubMed PubMed Citation Articles by Toshinai, K. Articles by Nakazato, M.

Des-Acyl Ghrelin Induces Food Intake by a Mechanism Independent of the Growth Hormone Secretagogue Receptor

Department of Internal Medicine (K.T., H.Y., Y.D., M.S.M., T.SH., T.K., M.N.), Miyazaki Medical College, University of Miyazaki, Miyazaki 889-1692, Japan; Department of Veterinary Physiology (N.M.), University of Miyazaki, Miyazaki 889-2151, Japan; Huffington Center on Aging (Y.S., R.G.S.), Baylor College of Medicine, Texas 77030; Department of Pharmacology (A.Y., T.SA.), University of Tsukuba, Ibaraki 305-8575, Japan; and National Cardiovascular Center Research Institute (M.M., K.K.), Osaka 565-8565, Japan

Address all correspondence and requests for reprints to: Masamitsu Nakazato, M.D., Ph.D., Third Department of Internal Medicine, Miyazaki Medical College, Miyazaki University, Kiyotake, Miyazaki 889-1692, Japan. E-mail: nakazato{at}med.miyazaki-u.ac.jp.

Ghrelin, an acylated peptide produced predominantly in the stomach, stimulates feeding and GH secretion via interactions with the GH secretagogue type 1a receptor (GHS-R1a), the functionally active form of the GHS-R. Ghrelin molecules exist in the stomach and hypothalamus as two major endogenous forms, a form acylated at serine 3 (ghrelin) and a des-acylated form (des-acyl ghrelin). Acylation is indispensable for the binding of ghrelin to the GHS-R1a. Ghrelin enhances feeding via the neuronal pathways of neuropeptide Y and orexin, which act as orexigenic peptides in the hypothalamus. We here studied the effect of des-acyl ghrelin on feeding behavior. Intracerebroventricular (icv) administration of rat des-acyl ghrelin to rats or mice fed ad libitum stimulated feeding during the light phase; neither ip nor icv administration of des-acyl ghrelin to fasting mice suppressed feeding. The icv administration of des-acyl ghrelin induced the expression of Fos, a marker of neuronal activation, in orexin-expressing neurons of the lateral hypothalamic area, but not neuropeptide Y-expressing neurons of the arcuate nucleus. Peripheral administration of des-acyl ghrelin to rats or mice did not affect feeding. Although icv administration of ghrelin did not induce food intake in GHS-R-deficient mice, it did in orexin-deficient mice. In contrast, icv administration of des-acyl ghrelin stimulated feeding in GHS-R-deficient mice, but not orexin-deficient mice. Des-acyl ghrelin increased the intracellular calcium concentrations in isolated orexin neurons. Central des-acyl ghrelin may activate orexin-expressing neurons, perhaps functioning in feeding regulation through interactions with a target protein distinct from the GHS-R.

This article has been cited by other articles:

				J. Liu, C. E. Prudom, R. Nass, S. S. Pezzoli, M. C. Oliveri, M. L. Johnson, P. Veldhuis, D. A. Gordon, A. D. Howard, D. R. Witcher, et al. Novel Ghrelin Assays Provide Evidence for Independent Regulation of Ghrelin Acylation and Secretion in Healthy Young Men J. Clin. Endocrinol. Metab., May 1, 2008; 93(5): 1980 - 1987. [Abstract] [Full Text] [PDF]

				J. D. Latshaw Daily Energy Intake of Broiler Chickens is Altered by Proximate Nutrient Content and Form of the Diet Poult. Sci., January 1, 2008; 87(1): 89 - 95. [Abstract] [Full Text] [PDF]

				M. Bossola, S. Giungi, L. Tazza, and G. Luciani Does desacyl ghrelin contribute to uraemic anorexia? Nephrol. Dial. Transplant., December 1, 2007; 22(12): 3673 - 3674. [Full Text] [PDF]

				T. Ando, Y. Ichimaru, F. Konjiki, M. Shoji, and G. Komaki Variations in the preproghrelin gene correlate with higher body mass index, fat mass, and body dissatisfaction in young Japanese women Am. J. Clinical Nutrition, July 1, 2007; 86(1): 25 - 32. [Abstract] [Full Text] [PDF]

				P. J. D. Delhanty, P. M. van Koetsveld, C. Gauna, B. van de Zande, G. Vitale, L. J. Hofland, and A. J. van der Lely Ghrelin and its unacylated isoform stimulate the growth of adrenocortical tumor cells via an anti-apoptotic pathway Am J Physiol Endocrinol Metab, July 1, 2007; 293(1): E302 - E309. [Abstract] [Full Text] [PDF]

				R. D Kineman, M. D Gahete, and R. M Luque Identification of a mouse ghrelin gene transcript that contains intron 2 and is regulated in the pituitary and hypothalamus in response to metabolic stress J. Mol. Endocrinol., May 1, 2007; 38(5): 511 - 521. [Abstract] [Full Text] [PDF]

				O. Alvarez-Garcia, E. Garcia-Lopez, J. Rodriguez, H. Gil-Pena, I. Molinos, E. Carbajo-Perez, and F. Santos Administration of ghrelin to young uraemic rats increases food intake transiently, stimulates growth hormone secretion and does not improve longitudinal growth Nephrol. Dial. Transplant., May 1, 2007; 22(5): 1309 - 1313. [Abstract] [Full Text] [PDF]

				M. Rauh, M. Groschl, and W. Rascher Simultaneous Quantification of Ghrelin and Desacyl-Ghrelin by Liquid Chromatography-Tandem Mass Spectrometry in Plasma, Serum, and Cell Supernatants Clin. Chem., May 1, 2007; 53(5): 902 - 910. [Abstract] [Full Text] [PDF]

				Y. Sun, J. M. Garcia, and R. G. Smith Ghrelin and Growth Hormone Secretagogue Receptor Expression in Mice during Aging Endocrinology, March 1, 2007; 148(3): 1323 - 1329. [Abstract] [Full Text] [PDF]

				A. S Bang, S. G Soule, T. G Yandle, A M. Richards, and C. J Pemberton Characterisation of proghrelin peptides in mammalian tissue and plasma J. Endocrinol., February 1, 2007; 192(2): 313 - 323. [Abstract] [Full Text] [PDF]

				D. H. St-Pierre, A. D. Karelis, L. Coderre, F. Malita, J. Fontaine, D. Mignault, M. Brochu, J.-P. Bastard, K. Cianflone, E. Doucet, et al. Association of Acylated and Nonacylated Ghrelin with Insulin Sensitivity in Overweight and Obese Postmenopausal Women J. Clin. Endocrinol. Metab., January 1, 2007; 92(1): 264 - 269. [Abstract] [Full Text] [PDF]

				E. Szentirmai, L. Kapas, and J. M. Krueger Ghrelin microinjection into forebrain sites induces wakefulness and feeding in rats Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2007; 292(1): R575 - R585. [Abstract] [Full Text] [PDF]

				K. Nonogaki, K. Nozue, and Y. Oka Hyperphagia Alters Expression of Hypothalamic 5-HT2C and 5-HT1B Receptor Genes and Plasma Des-Acyl Ghrelin Levels in Ay Mice Endocrinology, December 1, 2006; 147(12): 5893 - 5900. [Abstract] [Full Text] [PDF]

				A. E. Wertz-Lutz, T. J. Knight, R. H. Pritchard, J. A. Daniel, J. A. Clapper, A. J. Smart, A. Trenkle, and D. C. Beitz Circulating ghrelin concentrations fluctuate relative to nutritional status and influence feeding behavior in cattle J Anim Sci, December 1, 2006; 84(12): 3285 - 3300. [Abstract] [Full Text] [PDF]

				J. M. Zigman and J. K. Elmquist In search of an effective obesity treatment: A shot in the dark or a shot in the arm? PNAS, August 29, 2006; 103(35): 12961 - 12962. [Full Text] [PDF]

				H. ThidarMyint, H. Yoshida, T. Ito, and H. Kuwayama Dose-dependent response of plasma ghrelin and growth hormone concentrations to bovine ghrelin in Holstein heifers. J. Endocrinol., June 1, 2006; 189(3): 655 - 664. [Abstract] [Full Text] [PDF]