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9 - Ghrelin: an orexigenic signal from the stomach

Published online by Cambridge University Press:  15 September 2009

By
Tamas Horvath
Edited by
Jenni Harvey  and
Dominic J. Withers
Tamas Horvath
Affiliation:
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University, School of Medicine, New Haven, Connecticut 06520, USA
Jenni Harvey
Affiliation:
University of Dundee
Dominic J. Withers
Affiliation:
Imperial College of Science, Technology and Medicine, London
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Summary

Introduction

The discovery of ghrelin, a 28 amino-acid peptide hormone, has generated a substantial amount of attention for a number of reasons. Initially, ghrelin was heralded as the long sought endogenous ligand for the orphan growth hormone secretagogue receptors (GHS-Rs). Indeed, like growth hormone secretagogues (GHS), ghrelin targeted these receptors to potently increase the release of growth hormone (GH) both in vitro and in vivo. Soon, however, it became evident that ghrelin was implicated in a variety of physiological processes that include cell proliferation, metabolism, cell protection, reproduction, etc. Of these, the effects of ghrelin on food intake and metabolism have had the biggest impact; unlike other peripheral signals associated with energy balance, ghrelin increases appetite and leads to the accumulation of body fat. Indeed, the stimulatory effects of ghrelin on food intake and its apparent opposite relation to the anorectic hormone, leptin, have been proposed as the ying/yang model for hormonal regulation of energy balance. Nevertheless, the more is known about ghrelin, the more it becomes obvious that ghrelin produces its metabolic effects via a multitude of central and peripheral mechanisms that work in parallel to modulate the effects of ghrelin in energy regulation. This chapter will review the literature regarding the effects of ghrelin on energy balance. Energy balance implies the regulation of both food intake and energy expenditure, therefore we will discuss both topics in relation to ghrelin. A description of the possible central routes of ghrelin actions on energy balance within the brain will follow.

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Neurobiology of Obesity , pp. 266 - 284
Publisher: Cambridge University Press
Print publication year: 2008

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References

Andersson, U., Filipsson, K.et al. (2004). AMP-activated protein kinase plays a role in the control of food intake. J. Biol. Chem. 279, 12 005–8.CrossRefGoogle Scholar
Arafat, M. A., Otto, B.et al. (2005). Glucagon inhibits ghrelin secretion in humans. Eur. J. Endocrinol. 153, 397–402.CrossRefGoogle ScholarPubMed
Ariyasu, H., Takaya, K.et al. (2001). Stomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in humans. J. Clin. Endocrinol. Metab. 86, 4753–8.CrossRefGoogle ScholarPubMed
Asakawa, A., Inui, A.et al. (2003). Antagonism of ghrelin receptor reduces food intake and body weight gain in mice. Gut 52, 947–52.CrossRefGoogle ScholarPubMed
Banks, W. A., Tschop, M.et al. (2002). Extent and direction of ghrelin transport across the blood-brain barrier is determined by its unique primary structure. J. Pharmacol. Exp. Ther. 302, 822–7.CrossRefGoogle ScholarPubMed
Berridge, K. C. (1996). Food reward: brain substrates of wanting and liking. Neurosci. Biobehav. Rev. 20, 1–25.CrossRefGoogle Scholar
Bowers, C. Y. (1993). GH releasing peptides – structure and kinetics. J. Pediatr. Endocrinol. 6, 21–31.CrossRefGoogle ScholarPubMed
Bowers, C. Y., Momany, F. A.et al. (1984a). On the in vitro and in vivo activity of a new synthetic hexapeptide that acts on the pituitary to specifically release growth hormone. Endocrinology 114, 1537–45.CrossRefGoogle Scholar
Bowers, C. Y., Reynolds, G. A.et al. (1984b). New advances on the regulation of growth hormone (GH) secretion. Int. J. Neurol. 18, 188–205.Google Scholar
Broglio, F., Arvat, E.et al. (2002). Endocrine activities of cortistatin-14 and its interaction with GHRH and ghrelin in humans. J. Clin. Endocrinol. Metab. 87, 3783–90.CrossRefGoogle ScholarPubMed
Camina, J. P. (2006). Cell biology of the ghrelin receptor. J. Neuroendocrin. 18, 65–76.CrossRefGoogle ScholarPubMed
Camina, J. P., Carreira, M. C.et al. (2003). Regulation of ghrelin secretion and action. Endocrine 22, 5–12.CrossRefGoogle ScholarPubMed
Camina, J. P., Carreira, M. C.et al. (2004). Desensitization and endocytosis mechanisms of ghrelin-activated growth hormone secretagogue receptor 1a. Endocrinology 145, 930–40.CrossRefGoogle ScholarPubMed
Carreira, M. C., Camina, J. P.et al. (2004). Agonist-specific coupling of growth hormone secretagogue receptor type 1a to different intracellular signaling systems. Role of adenosine. Neuroendocrinology 79, 13–25.CrossRefGoogle ScholarPubMed
Chen, X., Ge, Y. L.et al. (2005). Effects of ghrelin on hypothalamic glucose responding neurons in rats. Brain Res. 1055, 131–6.CrossRefGoogle ScholarPubMed
Cone, R. D., Cowley, M. A.et al. (2001). The arcuate nucleus as a conduit for diverse signals relevant to energy homeostasis. Int. J. Obes. Relat. Metab. Disord. 25 (Suppl. 5), S63–7.CrossRefGoogle ScholarPubMed
Cowley, M. A. (2003). Hypothalamic melanocortin neurons integrate signals of energy state. Eur. J. Pharmacol. 480, 3–11.CrossRefGoogle ScholarPubMed
Cowley, M. A., Smith, R. G.et al. (2003). The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis. Neuron 37, 649–61.CrossRefGoogle ScholarPubMed
Cummings, D. E., Purnell, J. Q.et al. (2001). A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes 50, 1714–19.CrossRefGoogle ScholarPubMed
Cummings, D. E., Frayo, R. S.et al. (2004). Plasma ghrelin levels and hunger scores in humans initiating meals voluntarily without time- and food-related cues. Am. J. Physiol. Endocrinol. Metab. 287, E297–304.CrossRefGoogle ScholarPubMed
Davenport, A. P., Bonner, T. I.et al. (2005). International Union of Pharmacology. LVI. Ghrelin receptor nomenclature, distribution, and function. Pharmacol Rev. 57, 541–6.CrossRefGoogle Scholar
Deghenghi, R., Papotti, M.et al. (2001). Cortistatin, but not somatostatin, binds to growth hormone secretagogue (GHS) receptors of human pituitary gland. J. Endocrinol. Invest. 24, RC1–3.CrossRefGoogle Scholar
Dickson, S. L. & Luckman, S. M. (1997). Induction of c-fos messenger ribonucleic acid in neuropeptide Y and growth hormone (GH)-releasing factor neurons in the rat arcuate nucleus following systemic injection of the GH secretagogue, GH-releasing peptide-6. Endocrinology 138, 771–7.CrossRefGoogle ScholarPubMed
Dickson, S. L., Doutrelant-Viltart, O.et al. (1995a). GH-deficient dw/dw rats and lit/lit mice show increased Fos expression in the hypothalamic arcuate nucleus following systemic injection of GH-releasing peptide-6. J. Endocrinol. 146, 519–26.CrossRefGoogle Scholar
Dickson, S. L., Leng, G.et al. (1995b). Central actions of peptide and non-peptide growth hormone secretagogues in the rat. Neuroendocrinology 61, 36–43.CrossRefGoogle Scholar
Dickson, S. L., Doutrelant-Viltart, O.et al. (1996). Retrogradely labelled neurosecretory neurones of the rat hypothalamic arcuate nucleus express Fos protein following systemic injection of GH-releasing peptide-6. J. Endocrinol. 151, 323–31.CrossRefGoogle ScholarPubMed
Dickson, S. L., Viltart, O.et al. (1997). Attenuation of the growth hormone secretagogue induction of Fos protein in the rat arcuate nucleus by central somatostatin action. Neuroendocrinology 66, 188–94.CrossRefGoogle ScholarPubMed
Dickson, S. L., Bailey, A. R.et al. (1999). Growth hormone (GH) secretagogues and neuroendocrine regulation of GH secretion. Growth Horm. IGF Res. 9 (Suppl. A), 89–91.CrossRefGoogle ScholarPubMed
Drazen, D. L., Vahl, T. P.et al. (2006). Effects of a fixed meal pattern on ghrelin secretion: evidence for a learned response independent of nutrient status. Endocrinology 147, 23–30.CrossRefGoogle ScholarPubMed
Elmquist, J. K., Maratos-Flier, E.et al. (1998). Unraveling the central nervous system pathways underlying responses to leptin. Nat. Neurosci. 1, 445–50.CrossRefGoogle Scholar
Faulconbridge, L. F., Cummings, D. E.et al. (2003). Hyperphagic effects of brainstem ghrelin administration. Diabetes 52, 2260–5.CrossRefGoogle ScholarPubMed
Faulconbridge, L. F., Grill, H. J.et al. (2005). Distinct forebrain and caudal brainstem contributions to the neuropeptide Y mediation of ghrelin hyperphagia. Diabetes 54, 1985–93.CrossRefGoogle ScholarPubMed
Gaskin, F. S., Farr, S. A.et al. (2003). Ghrelin-induced feeding is dependent on nitric oxide. Peptides 24, 913–18.CrossRefGoogle ScholarPubMed
Gelling, R. W., Overduin, J.et al. (2004). Effect of uncontrolled diabetes on plasma ghrelin concentrations and ghrelin-induced feeding. Endocrinology 145, 4575–82.CrossRefGoogle ScholarPubMed
Grill, H. J. & Kaplan, J. M. (2001). Interoceptive and integrative contributions of forebrain and brainstem to energy balance control. Int. J. Obes. Relat. Metab. Disord. 25 (Suppl. 5), S73–7.CrossRefGoogle ScholarPubMed
Grill, H. J. & Kaplan, J. M. (2002). The neuroanatomical axis for control of energy balance. Front Neuroendocrinol. 23, 2–40.CrossRefGoogle ScholarPubMed
Guan, J. L., Wang, Q. P.et al. (2003). Synaptic interactions between ghrelin- and neuropeptide Y-containing neurons in the rat arcuate nucleus. Peptides 24, 1921–8.CrossRefGoogle ScholarPubMed
Guan, X. M., Yu, H.et al. (1997). Distribution of mRNA encoding the growth hormone secretagogue receptor in brain and peripheral tissues. Mol. Brain Res. 48, 23–9.CrossRefGoogle ScholarPubMed
Halem, H. A., Taylor, J. E.et al. (2004). Novel analogs of ghrelin: physiological and clinical implications. Eur. J. Endocrinol. 151 (Suppl. 1), S71–5.CrossRefGoogle ScholarPubMed
Halem, H. A., Taylor, J. E.et al. (2005). A novel growth hormone secretagogue-1a receptor antagonist that blocks ghrelin-induced growth hormone secretion but induces increased body weight gain. Neuroendocrinology 81, 339–49.CrossRefGoogle ScholarPubMed
Helmling, S., Maasch, C.et al. (2004). Inhibition of ghrelin action in vitro and in vivo by an RNA-Spiegelmer. Proc. Natl. Acad. Sci. USA 101, 13174–9.CrossRefGoogle ScholarPubMed
Holst, B. & Schwartz, T. W. (2004). Constitutive ghrelin receptor activity as a signaling set-point in appetite regulation. Trends. Pharmacol. Sci. 25, 113–17.CrossRefGoogle ScholarPubMed
Holst, B., Cygankiewicz, A.et al. (2003). High constitutive signaling of the ghrelin receptor – identification of a potent inverse agonist. Mol. Endocrinol. 17, 2201–10.CrossRefGoogle ScholarPubMed
Horvath, T. L. & Diano, S. (2004). The floating blueprint of hypothalamic feeding circuits. Nat. Rev. Neurosci. 5, 662–7.CrossRefGoogle ScholarPubMed
Horvath, T. L., Diano, S.et al. (2001). Minireview: ghrelin and the regulation of energy balance – a hypothalamic perspective. Endocrinology 142, 4163–9.CrossRefGoogle ScholarPubMed
Hosoda, H., Kojima, M.et al. (2000). Purification and characterization of rat des-Gln14-Ghrelin, a second endogenous ligand for the growth hormone secretagogue receptor. J. Biol. Chem. 275, 21 995–2000.CrossRefGoogle ScholarPubMed
Ishii, S., Kamegai, J.et al. (2002). Role of ghrelin in streptozotocin-induced diabetic hyperphagia. Endocrinology 143, 4934–7.CrossRefGoogle ScholarPubMed
Keen-Rhinehart, E. & Bartness, T. J. (2005). Peripheral ghrelin injections stimulate food intake, foraging, and food hoarding in Siberian hamsters. Am. J. Physiol. Regul. Integr. Comp. Physiol. 288, R716–22.CrossRefGoogle ScholarPubMed
Kim, M. S., Yoon, C. Y.et al. (2003). Changes in ghrelin and ghrelin receptor expression according to feeding status. Neuroreport 14, 1317–20.CrossRefGoogle ScholarPubMed
Kobelt, P., Helmling, S.et al. (2005). Anti-ghrelin Spiegelmer NOX-B11 inhibits neurostimulatory and orexigenic effects of peripheral ghrelin in rats. Gut. 55, 788–92.CrossRefGoogle ScholarPubMed
Kojima, M. & Kangawa, K. (2005). Ghrelin: structure and function. Physiol. Rev. 85, 495–522.CrossRefGoogle ScholarPubMed
Kojima, M., Hosoda, H.et al. (1999). Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402, 656–60.CrossRefGoogle ScholarPubMed
Lall, S., Tung, L. Y.et al. (2001). Growth hormone (GH)-independent stimulation of adiposity by GH secretagogues. Biochem. Biophys. Res. Commun. 280, 132–8.CrossRefGoogle ScholarPubMed
Lawrence, C. B., Snape, A. C.et al. (2002). Acute central ghrelin and GH secretagogues induce feeding and activate brain appetite centers. Endocrinology 143, 155–62.CrossRefGoogle ScholarPubMed
Roux, C. W., Neary, N. M.et al. (2005). Ghrelin does not stimulate food intake in patients with surgical procedures involving vagotomy. J. Clin. Endocrinol. Metab. 90, 4521–4.CrossRefGoogle ScholarPubMed
Locke, W., Kirgis, H. D.et al. (1995). Intracerebroventricular growth-hormone-releasing peptide-6 stimulates eating without affecting plasma growth hormone responses in rats. Life Sci 56, 1347–52.CrossRefGoogle ScholarPubMed
Lu, S., Guan, J. L.et al. (2002). Immunocytochemical observation of ghrelin-containing neurons in the rat arcuate nucleus. Neurosci. Lett. 321, 157–60.CrossRefGoogle ScholarPubMed
Malagon, M. M., Luque, R. M.et al. (2003). Intracellular signaling mechanisms mediating ghrelin-stimulated growth hormone release in somatotropes. Endocrinology 144, 5372–80.CrossRefGoogle ScholarPubMed
Masaoka, T., Suzuki, H.et al. (2003). Enhanced plasma ghrelin levels in rats with streptozotocin-induced diabetes. FEBS Lett. 541, 64–8.CrossRefGoogle ScholarPubMed
Matsubara, M., Sakata, I.et al. (2004). Estrogen modulates ghrelin expression in the female rat stomach. Peptides 25, 289–97.CrossRefGoogle ScholarPubMed
McKee, K. K., Palyha, O. C.et al. (1997). Molecular analysis of rat pituitary and hypothalamic growth hormone secretagogue receptors. Mol. Endocrinol. 11, 415–23.CrossRefGoogle ScholarPubMed
Mitchell, V., Bouret, S.et al. (2001). Comparative distribution of mRNA encoding the growth hormone secretagogue-receptor (GHS-R) in Microcebus murinus (Primate, lemurian) and rat forebrain and pituitary. J. Comp. Neurol. 429, 469–89.3.0.CO;2-#>CrossRefGoogle ScholarPubMed
Mozid, A. M., Tringali, G.et al. (2003). Ghrelin is released from rat hypothalamic explants and stimulates corticotrophin-releasing hormone and arginine-vasopressin. Horm. Metab. Res. 35, 455–9.Google ScholarPubMed
Nakagawa, E., Nagaya, N.et al. (2002). Hyperglycaemia suppresses the secretion of ghrelin, a novel growth-hormone-releasing peptide: responses to the intravenous and oral administration of glucose. Clin. Sci. (Lond) 103, 325–8.CrossRefGoogle ScholarPubMed
Nakazato, M., Murakami, N.et al. (2001). A role for ghrelin in the central regulation of feeding. Nature 409, 194–8.CrossRefGoogle ScholarPubMed
Naleid, A. M., Grace, M. K.et al. (2005). Ghrelin induces feeding in the mesolimbic reward pathway between the ventral tegmental area and the nucleus accumbens. Peptides 26, 2274–9.CrossRefGoogle ScholarPubMed
Neary, N. M., Small, C. J.et al. (2004). Ghrelin increases energy intake in cancer patients with impaired appetite: acute, randomized, placebo-controlled trial. J. Clin. Endocrinol. Metab. 89, 2832–6.CrossRefGoogle ScholarPubMed
Nogueiras, R., Tovar, S.et al. (2004). Regulation of growth hormone secretagogue receptor gene expression in the arcuate nuclei of the rat by leptin and ghrelin. Diabetes 53, 2552–8.CrossRefGoogle ScholarPubMed
Olszewski, P. K., Grace, M. K.et al. (2003a). Hypothalamic paraventricular injections of ghrelin: effect on feeding and c-Fos immunoreactivity. Peptides 24, 919–23.CrossRefGoogle Scholar
Olszewski, P. K., Li, D.et al. (2003b). Neural basis of orexigenic effects of ghrelin acting within lateral hypothalamus. Peptides 24, 597–602.CrossRefGoogle Scholar
Otto, B., Tschop, M.et al. (2004). Endogenous and exogenous glucocorticoids decrease plasma ghrelin in humans. Eur. J. Endocrinol. 151, 113–17.CrossRefGoogle ScholarPubMed
Pando, M. P. & Sassone-Corsi, P. (2001). Signaling to the mammalian circadian clocks: in pursuit of the primary mammalian circadian photoreceptor. Sci. STKE 2001(107), RE16.Google ScholarPubMed
Park, S., Sohn, S.et al. (2004). Fasting-induced changes in the hypothalamic-pituitary-GH axis in the absence of GH expression: lessons from the spontaneous dwarf rat. J. Endocrinol. 180, 369–78.CrossRefGoogle ScholarPubMed
Pinto, S., Roseberry, A. G.et al. (2004). Rapid rewiring of arcuate nucleus feeding circuits by leptin. Science 304, 110–15.CrossRefGoogle ScholarPubMed
Proulx, K., Vahl, T. P.et al. (2005). The effect of adrenalectomy on ghrelin secretion and orexigenic action. J. Neuroendocrinol. 17, 445–51.CrossRefGoogle ScholarPubMed
Riediger, T., Traebert, M.et al. (2003). Site-specific effects of ghrelin on the neuronal activity in the hypothalamic arcuate nucleus. Neurosci. Lett. 341, 151–5.CrossRefGoogle ScholarPubMed
Ritter, S. (1986). Glucoprivation and the Glucoprivic Control of Food Intake. Orlando, FL: Academic Press.CrossRefGoogle Scholar
Ritter, S., Dinh, T. T.et al. (2000). Localization of hindbrain glucoreceptive sites controlling food intake and blood glucose. Brain Res. 856, 37–47.CrossRefGoogle ScholarPubMed
Ruter, J., Kobelt, P.et al. (2003). Intraperitoneal injection of ghrelin induces Fos expression in the paraventricular nucleus of the hypothalamus in rats. Brain Res. 991, 26–33.CrossRefGoogle ScholarPubMed
Sato, T., Fukue, Y.et al. (2005). Molecular forms of hypothalamic ghrelin and its regulation by fasting and 2-deoxy-d-glucose administration. Endocrinology 146, 2510–16.CrossRefGoogle ScholarPubMed
Sawchenko, P. E. & Swanson, L. W. (1981). Central noradrenergic pathways for the integration of hypothalamic neuroendocrine and autonomic responses. Science 214, 685–7.CrossRefGoogle ScholarPubMed
Sawchenko, P. E. & Swanson, L. W. (1982). The organization of noradrenergic pathways from the brainstem to the paraventricular and supraoptic nuclei in the rat. Brain Res. 257, 275–325.CrossRefGoogle ScholarPubMed
Schmid, D. A., Held, K.et al. (2005). Ghrelin stimulates appetite, imagination of food, GH, ACTH, and cortisol, but does not affect leptin in normal controls. Neuropsychopharmacology 30, 1187–92.CrossRefGoogle Scholar
Seoane, L. M., Lopez, M.et al. (2003). Agouti-related peptide, neuropeptide Y, and somatostatin-producing neurons are targets for ghrelin actions in the rat hypothalamus. Endocrinology 144, 544–51.CrossRefGoogle ScholarPubMed
Shearman, L. P., Wang, S. P.et al. (2005). Ghrelin neutralization by an RNA-Spiegelmer ameliorates obesity in diet-induced obese mice. Endocrinology.Google ScholarPubMed
Shimbara, T., Mondal, M. S.et al. (2004). Central administration of ghrelin preferentially enhances fat ingestion. Neurosci. Lett. 369, 75–9.CrossRefGoogle ScholarPubMed
Shuto, Y., Shibasaki, T.et al. (2002). Hypothalamic growth hormone secretagogue receptor regulates growth hormone secretion, feeding, and adiposity. J. Clin. Invest. 109, 1429–36.CrossRefGoogle ScholarPubMed
Smith, R. G. (2005). Development of growth hormone secretagogues. Endocr. Rev. 26, 346–60.CrossRefGoogle ScholarPubMed
Smith, R. G., Palyha, O. C.et al. (1999). Growth hormone releasing substances: types and their receptors. Horm. Res. 51 (Suppl. 3), 1–8.Google ScholarPubMed
Smith, R. G., Jiang, H.et al. (2005). Developments in ghrelin biology and potential clinical relevance. Trends Endocrinol. Metab. 16, 436–42.CrossRefGoogle ScholarPubMed
Spiegelman, B. M. & Flier, J. S. (2001). Obesity and the regulation of energy balance. Cell 104, 531–43.CrossRefGoogle ScholarPubMed
St-Pierre, D. H., Karelis, A. D.et al. (2004). Relationship between ghrelin and energy expenditure in healthy young women. J. Clin. Endocrinol. Metab. 89, 5993–7.CrossRefGoogle ScholarPubMed
Sugino, T., Hasegawa, Y.et al. (2002a). A transient ghrelin surge occurs just before feeding in a scheduled meal-fed sheep. Biochem. Biophys. Res. Commun. 295, 255–60.CrossRefGoogle Scholar
Sugino, T., Yamaura, J.et al. (2002b). A transient surge of ghrelin secretion before feeding is modified by different feeding regimens in sheep. Biochem. Biophys. Res. Commun. 298, 785–8.CrossRefGoogle Scholar
Sun, Y., Ahmed, S.et al. (2003). Deletion of ghrelin impairs neither growth nor appetite. Mol. Cell. Biol. 23, 7973–81.CrossRefGoogle ScholarPubMed
Sun, Y., Wang, P.et al. (2004). Ghrelin stimulation of growth hormone release and appetite is mediated through the growth hormone secretagogue receptor. Proc. Natl. Acad. Sci. USA 101, 4679–84.CrossRefGoogle ScholarPubMed
Swanson, L. W. & Sawchenko, P. E. (1980). Paraventricular nucleus: a site for the integration of neuroendocrine and autonomic mechanisms. Neuroendocrinology 31, 410–17.CrossRefGoogle ScholarPubMed
Tang-Christensen, M., Vrang, N.et al. (2004). Central administration of ghrelin and agouti-related protein (83–132) increases food intake and decreases spontaneous locomotor activity in rats. Endocrinology 145, 4645–52.CrossRefGoogle ScholarPubMed
Torsello, A., Luoni, M.et al. (1998). Novel hexarelin analogs stimulate feeding in the rat through a mechanism not involving growth hormone release. Eur. J. Pharmacol. 360, 123–9.CrossRefGoogle Scholar
Torsello, A., Locatelli, V.et al. (2000). Differential orexigenic effects of hexarelin and its analogs in the rat hypothalamus: indication for multiple growth hormone secretagogue receptor subtypes. Neuroendocrinology 72, 327–32.CrossRefGoogle ScholarPubMed
Toshinai, K., Mondal, M. S.et al. (2001). Upregulation of Ghrelin expression in the stomach upon fasting, insulin-induced hypoglycemia, and leptin administration. Biochem. Biophys. Res. Commun. 281, 1220–5.CrossRefGoogle ScholarPubMed
Toshinai, K., Date, Y.et al. (2003). Ghrelin-induced food intake is mediated via the orexin pathway. Endocrinology 144, 1506–12.CrossRefGoogle ScholarPubMed
Traebert, M., Riediger, T.et al. (2002). Ghrelin acts on leptin-responsive neurones in the rat arcuate nucleus. J. Neuroendocrinol. 14, 580–6.CrossRefGoogle ScholarPubMed
Tritos, N. A. & Maratos-Flier, E. (1999). Two important systems in energy homeostasis: melanocortins and melanin-concentrating hormone. Neuropeptides 33, 339–49.CrossRefGoogle ScholarPubMed
Tschop, M., Smiley, D. L.et al. (2000). Ghrelin induces adiposity in rodents. Nature 407, 908–13.CrossRefGoogle ScholarPubMed
Tschop, M., Wawarta, R.et al. (2001). Post-prandial decrease of circulating human ghrelin levels. J. Endocrinol. Invest. 24, RC19–21.CrossRefGoogle ScholarPubMed
Lely, A. J., Tschop, M.et al. (2004). Biological, physiological, pathophysiological, and pharmacological aspects of ghrelin. Endocr. Rev. 25, 426–57.CrossRefGoogle ScholarPubMed
Wade, G. N. & Schneider, J. E. (1992). Metabolic fuels and reproduction in female mammals. Neurosci. Biobehav. Rev. 16, 235–72.CrossRefGoogle ScholarPubMed
Wellman, P. J., Davis, K. W.et al. (2005). Augmentation of cocaine hyperactivity in rats by systemic ghrelin. Regul. Pept. 125, 151–4.CrossRefGoogle ScholarPubMed
Williams, D. L., Grill, H. J.et al. (2003). Vagotomy dissociates short- and long-term controls of circulating ghrelin. Endocrinology 144, 5184–7.CrossRefGoogle Scholar
Wise, R. A. (2002). Brain reward circuitry: insights from unsensed incentives. Neuron 36, 229–40.CrossRefGoogle ScholarPubMed
Woods, S. C., Seeley, R. J.et al. (1998). Signals that regulate food intake and energy homeostasis. Science 280, 1378–83.CrossRefGoogle ScholarPubMed
Woods, S. C., Schwartz, M. W.et al. (2000). Food intake and the regulation of body weight. Annu. Rev. Psychol. 51, 255–77.CrossRefGoogle ScholarPubMed
Wortley, K. E., Anderson, K. D.et al. (2004). Genetic deletion of ghrelin does not decrease food intake but influences metabolic fuel preference. Proc. Natl. Acad. Sci. USA 101, 8227–32.CrossRefGoogle Scholar
Wortley, K. E., Del Rincon, J. P.et al. (2005). Absence of ghrelin protects against early-onset obesity. J. Clin. Invest. 115, 3573–8.CrossRefGoogle ScholarPubMed
Wren, A. M., Small, C. J.et al. (2000). The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion. Endocrinology 141, 4325–8.CrossRefGoogle ScholarPubMed
Wren, A. M., Seal, L. J.et al. (2001a). Ghrelin enhances appetite and increases food intake in humans. J. Clin. Endocrinol. Metab. 86, 5992.CrossRefGoogle Scholar
Wren, A. M., Small, C. J.et al. (2001b). Ghrelin causes hyperphagia and obesity in rats. Diabetes 50, 2540–7.CrossRefGoogle Scholar
Zhang, J. V., Ren, P. G.et al. (2005). Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake. Science 310, 996–9.CrossRefGoogle ScholarPubMed
Zigman, J. M., Nakano, Y.et al. (2005). Mice lacking ghrelin receptors resist the development of diet-induced obesity. J. Clin. Invest. 115, 3564–72.CrossRefGoogle ScholarPubMed
Zigman, J. M., Jones, J. E.et al. (2006). Expression of ghrelin receptor mRNA in the rat and the mouse brain. J. Comp. Neurol. 494, 528–48.CrossRefGoogle ScholarPubMed

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  • Ghrelin: an orexigenic signal from the stomach
    • By Tamas Horvath, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University, School of Medicine, New Haven, Connecticut 06520, USA
  • Edited by Jenni Harvey, University of Dundee, Dominic J. Withers, Imperial College of Science, Technology and Medicine, London
  • Book: Neurobiology of Obesity
  • Online publication: 15 September 2009
  • Chapter DOI: https://doi.org/10.1017/CBO9780511541643.010
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  • Ghrelin: an orexigenic signal from the stomach
    • By Tamas Horvath, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University, School of Medicine, New Haven, Connecticut 06520, USA
  • Edited by Jenni Harvey, University of Dundee, Dominic J. Withers, Imperial College of Science, Technology and Medicine, London
  • Book: Neurobiology of Obesity
  • Online publication: 15 September 2009
  • Chapter DOI: https://doi.org/10.1017/CBO9780511541643.010
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  • Ghrelin: an orexigenic signal from the stomach
    • By Tamas Horvath, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University, School of Medicine, New Haven, Connecticut 06520, USA
  • Edited by Jenni Harvey, University of Dundee, Dominic J. Withers, Imperial College of Science, Technology and Medicine, London
  • Book: Neurobiology of Obesity
  • Online publication: 15 September 2009
  • Chapter DOI: https://doi.org/10.1017/CBO9780511541643.010
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