Article contents
Ghrelin: a hormone regulating food intake and energy homeostasis
Published online by Cambridge University Press: 08 March 2007
Abstract
Core share and HTML view are not possible as this article does not have html content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.
Regulation of energy homeostasis requires precise coordination between peripheral nutrient-sensing molecules and central regulatory networks. Ghrelin is a twenty-eight-amino acid orexigenic peptide acylated at the serine 3 position mainly with an n-octanoic acid, which is produced mainly in the stomach. It is the endogenous ligand of the growth hormone secretagogue (GHS) receptors. Since plasma ghrelin levels are strictly dependent on recent food intake, this hormone plays an essential role in appetite and meal initiation. In addition, ghrelin is involved in the regulation of energy homeostasis. The ghrelin gene is composed of four exons and three introns and renders a diversity of orexigenic peptides as well as des-acyl ghrelin and obestatin, which exhibit anorexigenic properties. Ghrelin stimulates the synthesis of neuropeptide Y (NPY) and agouti-related protein (AgRP) in the arcuate nucleus neurons of the hypothalamus and hindbrain, which in turn enhance food intake. Ghrelin-expressing neurons modulate the action of both orexigenic NPY/AgRP and anorexigenic pro-opiomelanocortin neurons. AMP-activated protein kinase is activated by ghrelin in the hypothalamus, which contributes to lower intracellular long-chain fatty acids, and this appears to be the molecular signal for the expression of NPY and AgRP. Recent data suggest that ghrelin has an important role in the regulation of leptin and insulin secretion and vice versa. The present paper updates the effects of ghrelin on the control of energy homeostasis and reviews the molecular mechanisms of ghrelin synthesis, as well as interaction with GHS receptors and signalling. Relationships with leptin and insulin in the regulation of energy homeostasis are addressed.
- Type
- Review Article
- Information
- Copyright
- Copyright © The Nutrition Society 2006
References
Ahima, RS & Osei, SYMolecular regulation of eating behavior:new insights and prospects for therapeutic strategies. Trends Mol Med (2001) 7, 205–213.Google Scholar
Al Awar, R, Obeid, O, Hwalla, N & Azar, SPostprandial acylated ghrelin status following fat and protein manipulation of meals in healthy young women. Clin Sci (2005) 109, 405–411.Google Scholar
Andersson, U, Filipsson, K, Abbott, CR, Woods, A, Smith, K, Bloom, SR, Carling, D & Small, CJAMP-activated protein kinase plays a role in the control of food intake. J Biol Chem (2004) 279, 12005–12008.Google Scholar
Ariyasu, H, Takaya, K, Hosoda, H et al. Delayed short-term secretory regulation of ghrelin in obese animals: evidenced by a specific RIA for the active form of ghrelin. Endocrinology (2002) 143, 3341–3350.Google Scholar
Ariyasu, H, Takaya, K, Iwakura, H, Hosoda, H, Akamizu, T, Arai, Y, Kangawa, K & Nakao, KTransgenic mice overexpressing des-acyl ghrelin show small phenotype. Endocrinology (2005) 146, 355–364.Google Scholar
Arvat, E, Di Vito, L, Broglio, F, Papotti, M, Muccioli, G, Dieguez, C, Casanueva, FF, Deghenghi, R, Camanni, F & Ghigo, EPreliminary evidence that ghrelin, the natural GH secretagogue (GHS)-receptor ligand, strongly stimulates GH secretion in humans. J Endocrinol Invest (2000) 23, 493–495.Google Scholar
Asakawa, A, Inui, A, Fujimiya, M, Sakamaki, R, Shinfuku, N, Ueta, Y, Meguid, MM & Kasuga, MStomach regulates energy balance via acylated ghrelin and desacyl ghrelin. Gut (2005) 54, 18–24.Google Scholar
Asakawa, A, Inui, A, Kaga, T, Katsuura, G, Fujimiya, M, Fujino, MA & Kasuga, MAntagonism of ghrelin receptor reduces food intake and body weight gain in mice. Gut (2003) 52, 947–952.Google Scholar
Asakawa, A, Inui, A, Kaga, T et al. Ghrelin is an appetitestimulatory signal from stomach with structural resemblance to motilin. Gastroenterology (2001) 120, 337–345.Google Scholar
Atrens, DM, Sinden, JD, Penicaud, L, Devos, M & Le Magnen, JHypothalamic modulation of energy expenditure. Physiol Behav (1985) 35, 15–20.Google Scholar
Bacha, F & Arslanian, SAGhrelin suppression in overweight children: a manifestation of insulin resistance? J Clin Endocrinol Metab (2005) 90, 2725–2730.Google Scholar
Bagnasco, M, Dube, MG, Kalra, PS & Kalra, SPEvidence for the existence of distinct central appetite, energy expenditure, and ghrelin stimulation pathways as revealed by hypothalamic sitespecific leptin gene therapy. Endocrinology (2002) 143, 4409–4421.Google Scholar
Bagnasco, M, Tulipano, G, Melis, MR, Argiolas, A, Cocchi, D & Muller, EEEndogenous ghrelin is an orexigenic peptide acting in the arcuate nucleus in response to fasting. Regul Pept (2003) 111, 161–167.Google Scholar
Baile, CA, Della-Fera, MA & Martin, RJRegulation of metabolism and body fat mass by leptin. Annu Rev Nutr (2000) 20, 105–127.Google Scholar
Baldanzi, G, Filigheddu, N, Cutrupi, S et al. Ghrelin and desacyl ghrelin inhibit cell death in cardiomyocytes and endothelial cells through ERK1/2 and PI 3-kinase/AKT. J Cell Biol (2002) 159, 1029–1037.Google Scholar
Barazzoni, R, Bosutti, A, Stebel, M, Cattin, MR, Roder, E, Visintin, L, Cattin, L, Biolo, G, Zanetti, M & Guarnieri, GGhrelin regulates mitochondrial-lipid metabolism gene expression and tissue fat distribution in liver and skeletal muscle. Am J Physiol (2005) 288, E228–E235.Google Scholar
Barazzoni, R, Zanetti, M, Stebel, M, Biolo, G, Cattin, L & Guarnieri, GHyperleptinemia prevents increased plasma ghrelin concentration during short-term moderate caloric restriction in rats. Gastroenterology (2003) 124, 1188–1192.Google Scholar
Barkan, AL, Dimaraki, EV, Jessup, SK, Symons, KV, Ermolenko, M & Jaffe, CAGhrelin secretion in humans is sexually dimorphic, suppressed by somatostatin, and not affected by the ambient growth hormone levels. J Clin Endocrinol Metab (2003) 88, 2180–2184.Google Scholar
Batterham, RL, Cowley, MA, Small, CJ et al. Gut hormone PYY(3-36) physiologically inhibits food intake. Nature (2002) 418, 650–654.Google Scholar
Beaumont, NJ, Skinner, VO, Tan, TM et al. Ghrelin can bind to a species of high-density lipoprotein associated with paraoxonase. J Biol Chem (2003) 278, 8877–8880.Google Scholar
Bedendi, I, Alloatti, G, Marcantoni, A, Malan, D, Catapano, F, Ghe, C, Deghenghi, R, Ghigo, E & Muccioli, GCardiac effects of ghrelin and its endogenous derivatives des-octanoyl ghrelin and des-Gln14-ghrelin. Eur J Pharmacol (2003) 476, 87–95.Google Scholar
Bednarek, MA, Feighner, SD, Pong, SS, McKee, KK, Hreniuk, DL, Silva, MV, Warren, VA, Howard, ADVan Der Ploeg, LH & Heck, JVStructure–function studies on the new growth hormone-releasing peptide, ghrelin: minimal sequence of ghrelin necessary for activation of growth hormone secretagogue receptor 1a. J Med Chem (2000) 43 4370–4376Google Scholar
Beg, ZH, Allmann, DW & Gibson, DMModulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity with cAMP and with protein fractions of rat liver cytosol. Biochem Biophys Res Commun (1973) 54, 1362–1369.Google Scholar
Bercu, BB & Walker, RFNovel growth hormone secretagogues: clinical applications. Endocrinologist (1997) 7, 51–64.Google Scholar
Bing, C, Ambye, L, Fenger, M, Jorgensen, T, Borch-Johnsen, K, Madsbad, S & Urhammer, SALarge-scale studies of the Leu72Met polymorphism of the ghrelin gene in relation to the metabolic syndrome and associated quantitative traits. Diabet Med (2005) 22, 1157–1160.Google Scholar
Bowers, CYUnnatural growth hormone-releasing peptide begets natural ghrelin. J Clin Endocrinol Metab (2001) 8, 1464–1469.Google Scholar
Bowers, CY, Chang, J, Momany, FA & Folkers, KEffects of the enkephalins and enkephalin-analog on release of pituitary hormones in vitro. Proceedings of the 6th International Conference on Endocrinology, Molecular Endocrinology. In, [MacIntyre, I]. Amsterdam: Elsevier. (1977) 287Google Scholar
Broberger, C, Landry, M, Wong, H, Walsh, JN & Hokfelt, TSubtypes Y1 and Y2 of the neuropeptide Y receptor are respectively expressed in pro-opiomelanocortin- and neuropeptide-Y-containing neurons of the rat hypothalamic arcuate nucleus. Neuroendocrinology (1997) 66 393–408Google Scholar
Broglio, F, Arvat, E, Benso, A, Gottero, C, Muccioli, G, Papotti, M, van der Lely, AJ, Deghenghi, R & Ghigo, EGhrelin, a natural GH secretagogue produced by the stomach, induces hyperglycemia and reduces insulin secretion in humans. J Clin Endocrinol Metab (2001) 86 5083–5086Google Scholar
Broglio, F, Gottero, C, Prodam, F, Gauna, C, Muccioli, G, Papotti, M, Abribat, T, van der Lely, AJ & Ghigo, ENon-acylated ghrelin counteracts the metabolic but not the neuroendocrine response to acylated ghrelin in humans. J Clin Endocrinol Metab (2004) 89 3062–3065Google Scholar
Broglio, F, Koetsveld, PP, Benso, Aet al. Ghrelin secretion is inhibited by either somatostatin or cortistatin in humans. J Clin Endocrinol Metab (2002) 87 4829–4832Google Scholar
Callahan, HS, Cummings, DE, Pepe, MS, Breen, PA, Matthys, CC & Weigle, DSPostprandial suppression of plasma ghrelin level is proportional to ingested caloric load but does not predict intermeal interval in humans. J Clin Endocrinol Metab (2004) 89 1319–1324Google Scholar
Carlson, CA & Kim, KHRegulation of hepatic acetyl coenzyme A carboxylase by phosphorylation and dephosphorylation. J Biol Chem (1973) 248 378–380Google Scholar
Casanueva, FF & Diéguez, CGhrelin: the link connecting growth with metabolism and energy homeostasis. Rev Endocr Metab Disord (2002) 3 325–338Google Scholar
Cassoni, P, Ghe, C, Marrocco, T, Tarabra, E, Allia, E, Catapano, F, Deghenghi, R, Ghigo, E, Papotti, M & Muccioli, GExpression of ghrelin and biological activity of specific receptors for ghrelin and des-acyl ghrelin in human prostate neoplasms and related cell lines. Eur J Endocrinol (2004) 150 173–184Google Scholar
Chan, CB & Cheng, CHIdentification and functional characterization of two alternatively spliced growth hormone secretagogue receptor transcripts from the pituitary of black seabream Acanthopagrus schlegeli. Mol Cell Endocrinol (2004) 214 81–95Google Scholar
Chanoine, JP & Wong, ACGhrelin gene expression is markedly higher in fetal pancreas compared with fetal stomach: effect of maternal fasting. Endocrinology (2004) 145 3813–3820Google Scholar
Chen, CY, Chao, Y, Chang, FY, Chien, EJ, Lee, SD & Doong, MLIntracisternal des-acyl ghrelin inhibits food intake and non-nutrient gastric emptying in conscious rats. Int J Mol Med (2005 a) 16 695–699Google Scholar
Chen, CY, Inui, A, Asakawa, A, Fujino, K, Kato, I, Chen, CC, Ueno, N & Fujimiya, MDes-acyl ghrelin acts by CRF type 2 receptors to disrupt fasted stomach motility in conscious rats. Gastroenterology (2005 b) 129 8–25Google Scholar
Chen, HY, Trumbauer, ME, Chen, ASet al. Orexigenic action of peripheral ghrelin is mediated by neuropeptide Y and agoutirelated protein. Endocrinology (2004) 145 2607–2612Google Scholar
Cone, RDThe central melanocortin system and energy homeostasis. Trends Endocrinol Metab (1999) 10 211–216Google Scholar
Cone, RDAnatomy and regulation of the central melanocortin system. Nature Neurosci (2005) 8 571–578Google Scholar
Corbetta, S, Peracchi, M, Cappiello, V, Lania, A, Lauri, E, Vago, L, Beck-Peccoz, P & Spada, ACirculating ghrelin levels inpatients with pancreatic and gastrointestinal neuroendocrine tumors: identification of one pancreatic ghrelinoma. J Clin Endocrinol Metab (2003) 88 3117–3120Google Scholar
Cowley, MA, Smith, RG, Diano, Set al. The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis. Neuron (2003) 37 649–661Google Scholar
Culmsee, C, Monnig, J, Kemp, BE & Mattson, MPAMP-activated protein kinase is highly expressed in neurons in the developing rat brain and promotes neuronal survival following glucose deprivation. J Mol Neurosci (2001) 17 45–58Google Scholar
Cummings, DE & Foster, KEGhrelin–leptin tango in bodyweight regulation. Gastroenterology (2003) 124 1532–1535Google Scholar
Cummings, DE, Foster-Schubert, KE & Overduin, JGhrelin and energy balance: focus on current controversies. Curr Drug Targets (2005) 6 153–169Google Scholar
Cummings, DE, Purnell, JQ, Frayo, RS, Schmidova, K, Wisse, BE & Weigle, DSpreprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes (2001) 50 1714–1719Google Scholar
Cummings, DE & Shannon, MHGhrelin and gastric bypass: is there a hormonal contribution to surgical weight loss? J Clin Endocrinol Metab (2003) 88 2999–3002Google Scholar
Cummings, DE, Weigle, DS, Frayo, RS, Breen, PA, Ma, MK, Dellinger, EP & Purnell, JQPlasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. New Eng J Med (2002) 346 1623–1630Google Scholar
Date, Y, Kojima, M, Hosoda, H, Sawaguchi, A, Mondal, MS, Suganuma, T, Matsukura, S, Kangawa, K & Nakazato, MGhrelin, a novel growth hormone-releasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans. Endocrinology (2000) 141 4255–4261Google Scholar
Date, Y, Murakami, N, Toshinai, K, Matsukura, S, Niijima, A, Matsuo, H, Kangawa, K & Nakazato, MThe role of the gastric afferent vagal nerve in ghrelin-induced feeding and growth hormone secretion in rats. Gastroenterology (2002) 123 1120–1128Google Scholar
Date, Y, Nakazato, M, Murakami, N, Kojima, M, Kangawa, K & Matsukura, SGhrelin acts in the central nervous system to stimulate gastric acid secretion. Biochem Biophys Res Commun (2001) 280 904–907Google Scholar
Davis, JD, Wirtshafter, D, Asin, KE & Brief, DSustained intracerebroventricular infusion of brain fuels reduces body weight and food intake in rats. Science (1981) 212 81–83Google Scholar
De Smet, B, Depoortere, I, Moechars, D, Swennen, Q, Moreaux, B, Cryns, K, Tack, J, Buyse, JCoulie, B & Peeters, TLEnergy homeostasis and gastric emptying in ghrelin knockout mice. J Pharmacol Exp Ther (2006) 316 431–439Google Scholar
De Vriese, C, Gregoire, F, Lema-Kisoka, R, Waelbroeck, M, Robberecht, P & Delporte, CGhrelin degradation by serum and tissue homogenates: identification of the cleavage sites. Endocrinology (2004) 145 4997–5005Google Scholar
Del Rincón, JP, Thorner, MO & Gaylinn, BGMotilin-related peptide and ghrelin: lessons from molecular techniques, peptide chemistry, and receptor biology. Gastroenterology (2001) 120 587–588Google Scholar
Dixit, VD, Schaffer, EM, Pyle, RS, Collins, GD, Sakthivel, SK, Palaniappan, R, Lillard, JW Jr & Taub, DDGhrelin inhibits leptin- and activation-induced proinflammatory cytokine expression by human monocytes and T cells. J Clin Invest (2004) 114 57–66Google Scholar
Dockray, GLLuminal sensing in the gut; an overview. J Physiol Pharmacol (2003) 54 suppl. 4, 9–18Google Scholar
Druce, MR, Neary, NM, Small, CJ, Milton, J, Monteiro, M, Patterson, M, Ghatei, MA & Bloom, SRSubcutaneous administration of ghrelin stimulates energy intake in healthy lean human volunteers. Int J Obes (Lond) (2006) 30 293–296Google Scholar
Druce, MR, Small, CJ & Bloom, SRMinireview: gut peptides regulating satiety. Endocrinology (2004) 145 2660–2665Google Scholar
Egido, EM, Rodriguez-Gallardo, J, Silvestre, RA & Marco, JInhibitory effect of ghrelin on insulin and pancreatic somatostatin secretion. Eur J Endocrinol (2002) 146 241–244Google Scholar
English, PJ, Ghatei, MA, Malik, IA, Bloom, SR & Wilding, JPFood fails to suppress ghrelin levels in obese humans. J Clin Endocrinol Metab (2002) 87 2984–2987Google Scholar
Erdmann, J, Topsch, R, Lippl, F, Gussmann, P & Schusdziarra, VPostprandial response of plasma ghrelin levels to various test meals in relation to food intake, plasma insulin, and glucose. J Clin Endocrinol Metab (2004) 89 3048–3054Google Scholar
Flanagan, DE, Evans, ML, Monsod, TP, Rife, F, Heptulla, RA, Tamborlane, WV & Sherwin, RSThe influence of insulin on circulating ghrelin. Am J Physiol (2003) 284 E313–E316Google Scholar
Gauna, C, Delhanty, PJ, Hofland, LJ, Janssen, JA, Broglio, F, Ross, RJ, Ghigo, E & van der Lely, AJGhrelin stimulates, whereas des-octanoyl ghrelin inhibits, glucose output by primary hepatocytes. J Clin Endocrinol Metab (2005) 90 1055–1060Google Scholar
Gauna, C, Meyler, FM, Janssen, JA, Delhanty, PJ, Abribat, T, van Koetsveld, P, Hofland, LJ, Broglio, F, Ghigo, E & van der Lely, AJAdministration of acylated ghrelin reduces insulin sensitivity, whereas the combination of acylated plus unacylated ghrelin strongly improves insulin sensitivity. J Clin Endocrinol Metab (2004) 89 5035–5042Google Scholar
Gaytan, F, Barreiro, ML, Caminos, JEet al. Expression of ghrelin and its functional receptor, the type 1a growth hormone secretagogue receptor, in normal human testis and testicular tumors. J Clin Endocrinol Metab (2004) 89 400–409Google Scholar
Ghigo, E, Arvat, E, Giordano, Ret al. Biologic activities of growth hormone secretagogues in humans. Endocrine (2001) 14 87–93Google Scholar
Ghigo, E, Broglio, F, Arvat, E, Maccario, M, Papotti, M & Muccioli, GGhrelin: more than a natural GH secretagogue and/or an orexigenic factor. Clin Endocrinol (Oxf) (2005) 62 1–17Google Scholar
Gil, M, Villada, I, Aguilera, C, Linde, J, Ramírez-Tortosa, C, Cañete, R & Gil, APrepubertal obese children exhibit an altered postprandial plasma ghrelin pattern. Int J Obes (2004) 28 suppl. 1, 194Google Scholar
Gil-Campos, M Relaciones entre parámetros antropométricos, ingesta de nutrientes, hormonas y lípidos plasmáticos en niños obesos (Relationships between anthropometric parameters, nutrient intake, hormones and plasma lipids in obese children). PhD Thesis, University of Cordoba (2004)Google Scholar
Gil-Campos, M, Cañete, R & Gil, AHormones regulating lipid metabolism and plasma lipids in childhood obesity. Int J Obes Relat Metab Disord (2004 a) 28 S75–S80Google Scholar
Gil-Campos, M, Cañete, R & Gil, AAdiponectin, the missing link in insulin resistance and obesity. Clin Nutr (2004 b) 23 963–974Google Scholar
Giustina, A, Bonfanti, C, Licini, M, Ragni, G & Stefana, BHexarelin, a novel GHRP-6 analog, stimulates growth hormone (GH)release in a GH-secreting rat cell line (GH1) insensitive to GHreleasing hormone. Regul Pept (1997) 70 49–54Google Scholar
Gnanapavan, S, Kola, B, Bustin, SA, Morris, DG, McGee, P, Fairclough, P, Bhattacharya, S, Carpenter, R, Grossman, AB & Korbonits, MThe tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. J Clin Endocrinol Metab (2002) 87 2988–2991Google Scholar
Gropp, E, Shanabrough, M, Borok, Eet al. Agouti-related peptide-expressing neurons are mandatory for feeding. Nat Neurosci (2005) 8 1289–1291Google Scholar
Grove, KL & Cowley, MAIs ghrelin a signal for the development of metabolic systems? J Clin Invest (2005) 115 3393–3397Google Scholar
Guan, XM, Yu, H, Palyha, OC, McKee, KK, Feighner, SD, Sirinathsinghji, DJ, Smith, RG, Van der Ploeg, LH & Howard, ADDistribution of mRNA encoding the growth hormone secretagogue receptor in brain and peripheral tissues. Brain Res Mol Brain Res (1997) 48 23–29Google Scholar
Hahn, TM, Breininger, JF, Baskin, DG & Schwartz, MWCoexpression of AgRP and NPY in fasting-activated hypothalamic neurons. Nat Neurosci (1998) 1 271–272Google Scholar
Halem, HA, Taylor, JE, Dong, JZet al. Novel analogs of ghrelin:physiological and clinical implications. Eur J Endocrinol (2004) 151 suppl. 1, S71–S75Google Scholar
Halem, HA, Taylor, JE, Dong, JZ, Shen, Y, Datta, R, Abizaid, A, Diano, S, Horvath, TL & Culler, MDA novel growth hormone secretagogue-1a receptor antagonist that blocks ghrelin-induced growth hormone secretion but induces increased body weight gain. Neuroendocrinology (2005) 81 339–349Google Scholar
Haqq, AM, Farooqi, IS, O'Rahilly, S, Stadler, DD, Rosenfeld, RG, Pratt, KL, LaFranchi, SH & Purnell, JQSerum ghrelin levels are inversely correlated with body mass index, age, and insulin concentrations in normal children and are markedly increased in Prader–Willi syndrome. J Clin Endocrinol Metab (2003) 88 174–178Google Scholar
Hardie, DG, Salt, IP, Hawley, SA & Davies, SPAMP-activated protein kinase: an ultrasensitive system for monitoring cellular energy charge. Biochem J (1999) 338 717–722Google Scholar
Haskell-Luevano, C, Chen, P, Li, C, Chang, K, Smith, MS, Cameron, JL & Cone, RDCharacterization of the neuroanatomical distribution of agouti-related protein immunoreactivity in the rhesus monkey and the rat. Endocrinology (1999) 140 1408–1415Google Scholar
Heller, RS, Jenny, M, Collombat, P, Mansouri, A, Tomasetto, C, Madsen, OD, Mellitzer, G, Gradwohl, G & Serup, PGenetic determinants of pancreatic epsilon-cell development. Dev Biol (2005) 28 217–224Google Scholar
Hewson, AK & Dickson, SLSystemic administration of ghrelin induces Fos and Egr-1 proteins in the hypothalamic arcuate nucleus of fasted and fed rats. J Neuroendocrinol (2000) 12 1047–1049Google Scholar
Hinney, A, Hoch, A, Geller, F, Schafer, H, Siegfried, W, Goldschmidt, H, Remschmidt, H & Hebebrand, JGhrelin gene: identification of missense variants and a frameshift mutation in extremely obese children and adolescents and healthy normal weight students. J Clin Endocrinol Metab (2002) 87 2716Google Scholar
Hirsh, D, Heinrichs, C, Leenders, B, Wong, AC, Cummings, DE & Chanoine, JPGhrelin is suppressed by glucagon and does not mediate glucagon-related growth hormone release. Horm Res (2005) 63 111–118Google Scholar
Holdstock, C, Engstrom, BE, Ohrvall, M, Lind, L, Sundbom, M & Karlsson, FAGhrelin and adipose tissue regulatory peptides: effect of gastric bypass surgery in obese humans. J Clin Endocrinol Metab (2003) 88 3177–3183Google Scholar
Holst, B, Cygankiewicz, A, Jensen, TH, Ankersen, M & Schwartz, TWHigh constitutive signaling of the ghrelin receptor identification of a potent inverse agonist. Mol Endocrinol (2003) 17 2201–2210Google Scholar
Horvath, TLThe hardship of obesity: a soft-wired hypothalamus. Nat Neurosci (2005) 8 561–565Google Scholar
Horvath, TL, Diano, S, Sotonyi, P, Heiman, M & Tschop, MMinireview: ghrelin and the regulation of energy balance – a hypothalamic perspective. Endocrinology (2001) 142 4163–4169Google Scholar
Hosoda, H, Kojima, M, Matsuo, H & Kangawa, KGhrelin and des-acyl ghrelin: two major forms of rat ghrelin peptide in gastrointestinal tissue. Biochem Biophys Res Commun (2000 a) 279 909–913Google Scholar
Hosoda, H, Kojima, M, Matsuo, H & Kangawa, KPurification and characterization of rat des-Gln14-ghrelin, a second endogenous ligand for the growth hormone secretagogue receptor. J Biol Chem (2000 b) 275 21995–22000Google Scholar
Hosoda, H, Kojima, M, Mizushima, T, Shimizu, S & Kangawa, KStructural divergence of human ghrelin. Identification of multiple ghrelin-derived molecules produced by post-translational processing. J Biol Chem (2003) 278 64–70Google Scholar
Howard, AD, Feighner, SD, Cully, DFet al. A receptor in pituitary and hypothalamus that functions in growth hormone release. Science (1996) 273 974–977Google Scholar
Huszar, D, Lynch, CA, Fairchild-Huntress, Vet al. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell (1997) 88 131–141Google Scholar
Ikezaki, A, Hosoda, H, Ito, K, Iwama, S, Miura, N, Matsuoka, H, Kondo, C, Kojima, M, Kangawa, K & Sugihara, SFasting plasma ghrelin levels are negatively correlated with insulin resistance and PAI-1, but not with leptin, in obese children and adolescents. Diabetes (2002) 51 3408–3411Google Scholar
Jacobowitz, DM & O'Donohue, TLα-Melanocyte stimulating hormone: immunohistochemical identification and mapping in neurons of rat brain. Proc Natl Acad Sci U S A (1978) 75 6300–6304Google Scholar
Jeffery, PL, Duncan, RP, Yeh, AH, Jaskolski, RA, Hammond, DS, Herington, AC & Chopin, LKExpression of the ghrelin axis in the mouse: an exon 4-deleted mouse proghrelin variant encodes a novel C terminal peptide. peptide. Endocrinology (2005) 146 432–440Google Scholar
Kaiya, H, Kojima, M, Hosoda, H, Koda, A, Yamamoto, K, Kitajima, Y, Matsumoto, M, Minamitake, Y, Kikuyama, S & Kangawa, KBullfrog ghrelin is modified by n-octanoic acid at its third threonine residue. J Boil Chem (2001) 276 40441–40448Google Scholar
Kaiya, H, Kojima, M, Hosoda, H, Riley, LG, Hirano, T, Grau, EG & Kangawa, KIdentification of tilapia ghrelin and its effects on growth hormone and prolactin release in the tilapia, Oreochromis mossambicus. Comp Biochem Physiol (2003) 135B 421–429Google Scholar
Kalra, SP, Bagnasco, M, Otukonyong, EE, Dube, MG & Kalra, PSRhythmic, reciprocal ghrelin and leptin signaling: new insight in the development of obesity. Regul Pept (2003) 111 1–11Google Scholar
Kalra, SP & Kalra, PSNeuropeptide Y: a physiological orexigen modulated by the feedback action of ghrelin and leptin. Endocrine (2003) 22 49–56Google Scholar
Kalra, SP, Ueno, N & Kalra, PSStimulation of appetite by ghrelin is regulated by leptin restraint: peripheral and central sites of action. J Nutr (2005) 135 1331–1335Google Scholar
Kamegai, J, Tamura, H, Shimizu, T, Ishii, S, Sugihara, H & Wakabayashi, IChronic central infusion of ghrelin increases hypothalamic neuropeptide Y and agouti-related protein mRNA levels and body weight in rats. Diabetes (2001) 50 2438–2443Google Scholar
Kanamoto, N, Akamizu, T, Tagami, T, Hataya, Y, Moriyama, K, Takaya, K, Hosoda, H, Kojima, M, Kangawa, K & Nakao, KGenomic structure and characterization of the 5′-flanking region of the human ghrelin gene. Endocrinology (2004) 145 4144–4153Google Scholar
Kelley, AE & Berridge, KCThe neuroscience of natural rewards: relevance to addictive drugs. J Neurosci (2002) 22 3306–3311Google Scholar
Kemp, BE, Stapleton, D, Campbell, DJet al. AMP-activated protein kinase, super metabolic regulator. Biochem Soc Trans (2003) 31 162–168Google Scholar
Kim, MS & Lee, KURole of hypothalamic 5′-AMP-activated protein kinase in the regulation of food intake and energy homeostasis. J Mol Med (2005) 83 514–520Google Scholar
Kim, MS, Namkoong, C, Kim, HS, Jang, PG, Kim Pak, YM, Katakami, H, Park, JY & Lee, KUChronic central administration of ghrelin reverses the effects of leptin. Int J Obes Relat Metab Disord (2004) 28 1264–1271Google Scholar
Kim, SW, Her, SJ, Park, SJ, Kim, D, Park, KS, Lee, HK, Han, BH, Kim, MS, Shin, CS & Kim, SYGhrelin stimulates proliferation and differentiation and inhibits apoptosis in osteoblastic MC3T3-E1 cells. Bone (2005) 37 359–369Google Scholar
Kishimoto, M, Okimura, Y, Nakata, H, Kudo, T, Iguchi, G, Takahashi, Y, Kaji, H & Chihara, KCloning and characterization of the 5(′)-flanking region of the human ghrelin gene. Biochem Biophys Res Commun (2003) 305 186–192Google Scholar
Kleinz, MJ, Maguire, JJ, Skepper, JN & Davenport, APFunctional and immunocytochemical evidence for a role of ghrelin and des-octanoyl ghrelin in the regulation of vascular tone in man. Cardiovasc Res (2006) 69 227–235Google Scholar
Kohno, D, Gao, HZ, Muroya, S, Kikuyama, S & Yada, TGhrelin directly interacts with neuropeptide-Y-containing neurons in the rat arcuate nucleus: Ca2+ signaling via protein kinase A and N-type channel-dependent mechanisms and cross-talk with leptin and orexin. Diabetes (2003) 52 948–956Google Scholar
Kojima, M, Hosoda, H, Date, Y, Nakazato, M, Matsuo, H & Kangawa, KGhrelin is a growth-hormone-releasing acylated peptide from stomach. Nature (1999) 402 656–660Google Scholar
Kojima, M, Hosoda, H & Kangawa, KClinical endocrinology and metabolism. Ghrelin, a novel growth-hormone-releasing and appetite-stimulating peptide from stomach. Best Pract Res Clin Endocrinol Metab (2004) 18 517–530Google Scholar
Kojima, M, Hosoda, H, Matsuo, H & Kangawa, KGhrelin: discovery of the natural endogenous ligand for the growth hormone secretagogue receptor. Trends Endocrinol Metab (2001) 12 118–122Google Scholar
Konturek, PC, Konturek, JW, Czesnikiewicz-Guzik, M, Brzozowski, T, Sito, E & Konturek, PCNeuro-hormonal control of food intake; basic mechanisms and clinical implications. J Physiol Pharmacol (2005) 56 suppl. 6, 5–25Google Scholar
Konturek, SJ, Konturek, JW, Pawlik, T & Brzozowski, YBrain–gut axis and its role in the control of food intake. J Physiol Pharmacol (2004) 55 137–154Google Scholar
Konturek, SJ, Pepera, J, Zabielski, K, Konturek, PC, Pawlik, T, Szlachcic, A & Hahn, EGBrain–gut axis in pancreatic secretion and appetite control. J Physiol Pharmacol (2003) 54 293–317Google Scholar
Korbonits, M, Bustin, SA, Kojima, M, Jordan, S, Adams, EF, Lowe, DG, Kangawa, K & Grossman, ABThe expression of the growth hormone secretagogue receptor ligand ghrelin in normal and abnormal human pituitary and other neuroendocrine tumors. J Clin Endocrinol Metab (2001) 86 881–887Google Scholar
Korbonits, M, Gueorguiev, M, O'Grady, E, Lecoeur, C, Swan, DC, Mein, CA, Weill, J, Grossman, AB & Froguel, PA variation in the ghrelin gene increases weight and decreases insulin secretion in tall, obese children. J Clin Endocrinol Metab (2002) 87 4005–4008Google Scholar
Lam, TK, Schwartz, GJ & Rossetti, LHypothalamic sensing of fatty acids. Nat Neurosci (2005) 8 579–584Google Scholar
Langenberg, C, Bergstrom, J, Laughlin, GA & Barrett-Connor, EGhrelin and the metabolic syndrome in older adults. J Clin Endocrinol Metab (2005) 90 6448–6453Google Scholar
Larsen, LH, Gjesing, AP, Sorensen, TI, Hamid, YH, Echwald, SM, Toubro, S, Black, E, Astrup, A, Hansen, T & Pedersen, OMutation analysis of the preproghrelin gene: no association with obesity and type 2 diabetes. Clin Biochem (2005) 38 420–424Google Scholar
Le Roux, CW, Neary, NM, Halsey, TJ, Small, CJ, Martinez-Isla, AM, Ghatei, MA, Theodorou, NA & Bloom, SRGhrelin does not stimulate food intake in patients with surgical procedures involving vagotomy. J Clin Endocrinol Metab (2005 a) 90 4521–4524Google Scholar
Le Roux, CW, Patterson, M, Vincent, RP, Hunt, C, Ghatei, MA & Bloom, SRPostprandial plasma ghrelin is suppressed proportional to meal calorie content in normal-weight but not obese subjects. J Clin Endocrinol Metab (2005 b) 90 1068–1071Google Scholar
Lee, HM, Wang, G, Englander, EW, Kojima, M & Greeley, GH JrGhrelin, a new gastrointestinal endocrine peptide that stimulates insulin secretion: enteric distribution, ontogeny, influence of endocrine, and dietary manipulations. Endocrinology (2002) 143 185–190Google Scholar
Lucidi, P, Murdolo, G, Di Loreto, C, De Cicco, A, Parlanti, N, Fanelli, C, Santeusanio, F, Bolli, GB & De Feo, PGhrelin is not necessary for adequate hormonal counterregulation of insulin-induced hypoglycemia. Diabetes (2002) 51 2911–2914Google Scholar
Maffeis, C, Bonadonna, RC, Consolaro, A, Vettor, R, Banzato, C, Silvagni, D, Bogoni, G, Pellegrino, M & Tato, LGhrelin, insulin sensitivity and postprandial glucose disposal in overweight and obese children. Eur J Endocrinol (2006) 154 61–68Google Scholar
Malagon, MM, Luque, RM, Ruiz-Guerrero, E, Rodriguez-Pacheco, F, Garcia-Navarro, S, Casanueva, FF, Gracia-Navarro, F & Castano, JPIntracellular signaling mechanisms mediating ghrelinstimulated growth hormone release in somatotropes. Endocrinology (2003) 144 5372–5380Google Scholar
Masuda, Y, Tanaka, T, Inomata, N, Ohnuma, N, Tanaka, S, Itoh, Z, Hosoda, H, Kojima, M & Kangawa, KGhrelin stimulates gastric acid secretion and motility in rats. Biochem Biophys Res Commun (2000) 276 905–908Google Scholar
Matsumoto, M, Hosoda, H, Kitajima, Y, Morozumi, N, Minamitake, Y, Tanaka, S, Matsuo, H, Kojima, M, Hayashi, Y & Kangawa, KStructure–activity relationship of ghrelin: pharmacological study of ghrelin peptides. Biochem Biophys Res Commun (2001) 287 42–46Google Scholar
Matzinger, D, Degen, L, Drewe, J, Meuli, J, Duebendorfer, R, Ruckstuhl, N, D'Amato, M, Rovati, L & Beglinger, CThe role of long chain fatty acids in regulating food intake and cholecystokinin release in humans. Gut (2000) 46 688–693Google Scholar
Mayer, JRegulation of energy intake and the body weight: the glucostatic theory and the lipostatic hypothesis. Ann N Y Acad Sci (1955) 63 15–43Google Scholar
Minokoshi, Y, Alquier, T, Furukawa, Net al. AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus. Nature (2004) 428 569–574Google Scholar
Minokoshi, Y, Haque, MS & Shimazu, TMicroinjection of leptin into the ventromedial hypothalamus increases glucose uptake in peripheral tissues in rats. Diabetes (1999) 48 287–291Google Scholar
Mohlig, M, Koebnick, C, Weickert, MO, Lueder, W, Otto, B, Steiniger, J, Twilfert, M, Meuser, F, Pfeiffer, AF & Zunft, HJrabinoxylan-enriched meal increases serum ghrelin levels in healthy humans. Horm Metab Res (2002) 37 303–308Google Scholar
Mohlig, M, Spranger, J, Otto, B, Ristow, M, Tschop, M & Pfeiffer, AFEuglycemic hyperinsulinemia, but not lipid infusion, decreases circulating ghrelin levels in humans. J Endocrinol Invest (2002) 25 RC36–RC38Google Scholar
Moran, LJ, Luscombe-Marsh, ND, Noakes, M, Wittert, GA, Keogh, JB & Clifton, PMThe satiating effect of dietary protein is unrelated to postprandial ghrelin secretion. J Clin Endocrinol Metab (2005) 90 5205–5211Google Scholar
Muccioli, G, Papotti, M, Locatelli, V, Ghigo, E & Deghenghi, RBinding of 125I-labeled ghrelin to membranes from human hypothalamus and pituitary gland. J Endocrinol Invest (2001) 24 RC7–RC9Google Scholar
Muccioli, G, Pons, N, Ghe, C, Catapano, F, Granata, R & Ghigo, EGhrelin and des-acyl ghrelin both inhibit isoproterenolinduced lipolysis in rat adipocytes via a non-type 1a growth hormone secretagogue receptor. Eur J Pharmacol (2004) 498 27–35Google Scholar
Muller, AF, Lamberts, SW, Janssen, JA, Hofland, LJ, Koetsveld, PV, Bidlingmaier, M,Strasburger, CJ,Ghigo, E & van der Lely, AJGhrelin drives GH secretion during fasting in man. Eur J Endocrinol (2002) 146 203–207Google Scholar
Murashita, M, Kusumi, I, Inoue, T, Takahashi, Y, Hosoda, H, Kangawa, K, Koyama, TOlanzapine increases plasma ghrelin level in patients with schizophrenia. Psychoneuroendocrinology (2005) 30 106–110Google Scholar
Murata, M, Okimura, Y, Iida, K,Matsumoto, M,Sowa, H,Kaji, H,Kojima, M,Kangawa, K & Chihara, KGhrelin modulates the downstream molecules of insulin signaling in hepatoma cells. J Biol Chem (2002) 15, 5667–5674.Google Scholar
Mustonen, AM, Nieminen, P & Hyvarinen, HPreliminary evidence that pharmacologic melatonin treatment decreases rat ghrelin levels. Endocrine (2001) 16, 43–46.Google Scholar
Nagaya, N, Kojima, M, Uematsu, M,Yamagishi, M,Hosoda, H,Oya, H,Hayashi, Y & Kangawa, KHemodynamic and hormonal effects of human ghrelin in healthy volunteers. Am J Physiol (2001 a) 280,R1483–R1487.Google Scholar
Nagaya, N, Miyatake, K, Uematsu, M,Oya, H,Shimizu, W,Hosoda, H,Kojima, M,Nakanishi, N,Mori, H & Kangawa, WHemodynamic, renal, and hormonal effects of ghrelin infusion in patients with chronic heart failure. J Clin Endocrinol Metab (2001 b) 86,5854–5859.Google Scholar
Nakagawa, E, Nagaya, N, Okumura, H,Enomoto, M,Oya, H,Ono, F,Hosoda, H,Kojima, M &Kangawa, KHyperglycaemia suppresses the secretion of ghrelin, a novel growth-hormone-releasing peptide: responses to the intravenous and oral administration of glucose. Clin Sci (Lond) (2002) 103,325–328.Google Scholar
Nakai, Y, Hosoda, H, Nin, K,Ooya, C,Hayashi, H,Akamizu, T & Kangawa, kPlasma levels of active form of ghrelin during oral glucose tolerance test in patients with anorexia nervosa. Eur J Endocrinol (2003) 149,R001–R003.Google Scholar
Nakazato, M, Murahami, N, Date, M,Kojima, M,Matsuo, H,Kangawa, K & Matsukura, SARole for ghrelin in the central regulation of feeding. Nature (2001) 409,194–198.Google Scholar
Naleid, AM, Grace, MK, Cummings, DE & Levine, ASGhrelin induces feeding in the mesolimbic reward pathway between the ventral tegmental area and the nucleus accumbens. Peptides (2005) 26,2274–2279.Google Scholar
Obici, S, Feng, Z, Tan, J,Liu, L,Karkanias, G – Rossetti, LCentral
melanocortin receptors regulate insulin action.J Clin Invest
(2001) 108,1079–1085.Google Scholar
Obici, S, Zhang, BB, Karkanias, G & Rossetti, LHypothalamic insulin signaling is required for inhibition of glucose production. Nat Med (2002) 8,1376–1382.Google Scholar
Ott, V, Fasshauer, M, Dalski, A,Meier, B,Perwitz, N,Klein, HH,Tschop, M & Klein, JDirect peripheral effects of ghrelin include suppression of adiponectin expression. Horm Metab Res (2002) 34,640–645.Google Scholar
Otto, B, Spranger, J, Benoit, SC,Clegg, DJ – Tschop, MHThe many faces of ghrelin: new perspectives for nutrition research? Br J Nutr (2005) 93,765–771.Google Scholar
Otukonyong, EE, Dube, MG, Torto, R,Kalra, PS & Kalra, spHigh-fat diet-induced ultradian leptin and insulin hypersecretion are absent in obesity-resistant rats. Obes Res (2005) 13,991–999.Google Scholar
Shrestha, YB, Wickwire, K & Giraudo, SQRole of AgRP on ghrelin-induced feeding in the hypothalamic paraventricular
nucleus. Regul Pept (2006) 133,68–73.Google Scholar
Silva-Elipe, MV, Bednarek, MA & Gao, YD1H NMR structural analysis of human ghrelin and its six truncated analogs. Biopolymers (2001) 59,489–501.Google Scholar
Smith, RG, Jiang, H & Sun, YDevelopments in ghrelin biology and potential clinical relevance. Trends Endocrinol Metab (2005) 16,436–442.Google Scholar
Snitker, S, Tataranni, PA & Ravussin, ERespiratory quotient is inversely associated with muscle sympathetic nerve activity J Clin Endocrinol Metab (1998) 83,3977–3979.Google Scholar
Soriano-Guillen, L, Barrios, V, Campos-Barros, A & Argente, J (2004) Ghrelin levels in obesity and anorexia nervosa: effect of weight reduction or recuperation. J Pediatr 144,36–42.Google Scholar
Soule, S, Pemberton, C, Hunt, P,Cole, D,Raudsepp, S & Inder, WPrandial regulation of ghrelin secretion in humans: does glucagon contribute to the preprandial increase in circulating ghrelin? Clin Endocrinol (Oxf) (2005) 63,412–417.Google Scholar
Steinle, NI, Pollin, TI, O'Connell, JR, Mitchell, BD & Shuldiner, ARVariants in the ghrelin gene are associated with metabolic syndrome in the Old Order Amish. J Clin Endocrinol Metab (2005) 90,6672–6677.Google Scholar
Sun, Y, Ahmed, S & Smith, RGDeletion of ghrelin impairs neither growth nor appetite. Mol Cell Biol (2003) 23,7973–7981.Google Scholar
Sun, Y, Wang, P, Zheng, H & Smith, RGGhrelin stimulation of growth hormone release and appetite is mediated through the growth hormone secretagogue receptor. Proc Natl Acad Sci U S A (2004) 101,4679–4684.Google Scholar
Takaya, K, Ariyasu, H, Kanamoto, N, et al..Ghrelin strongly stimulates growth hormone release in humans. J Clin Endocrinol Metab (2000) 85,4908–4911.Google Scholar
Tamura, H, Kamegai, J, Shimizu, T,Ishii, SSugihara, H & Oikawa, SGhrelin stimulates GH but not food intake in arcuate nucleus ablated rats. Endocrinology (2002) 143,3268–3275.Google Scholar
Tanaka, M, Hayashida, Y, Iguchi, T,Nakao, N,Nakai, N & Nakashima, KOrganization of the mouse ghrelin gene and promoter:occurrence of a short noncoding first exon. Endocrinology (2001) 142,3697–3700.Google Scholar
Tanaka, M, Naruo, T, Muranaga, T,Yasuhara, D,Shiiya, T,Nakazato, M,Matsukura, S & Nozoe, SIncreased fasting plasma ghrelin levels in patients with bulimia nervosa. Eur J Endocrinol (2002) 146,R1–R3.Google Scholar
Teff, KL, Elliott, SS, Tschop, M,Kieffer, TJ, Rader, D, Heiman, M, Townsend, RR, Keim, NL, D'Alessio, D – Havel, PJDietary fructose reduces circulating insulin and leptin, attenuates postprandial suppression of ghrelin, and increases triglycerides in women. J Clin Endocrinol Metab (2004) 89,2963–2972.Google Scholar
Tena-Sempere, MGhrelin: novel regulator of gonadal function. J Endocrinol Invest (2005) 28,26–29.Google Scholar
Thompson, NM, Gill, DA, Davies, R,Loveridge, N,Houston, PA,Robinson, IC & Wells, TGhrelin and des-octanoyl ghrelin promote adipogenesis directly in vivo by a mechanism independent of the type 1a growth hormone secretagogue receptor. Endocrinology (2004) 145,234–242.Google Scholar
Tolle, V, Kadem, M, Bluet-Pajot, MT,et al.. Balance in ghrelin and leptin plasma levels in anorexia nervosa patients and constitutionally thin women. J Clin Endocrinol Metab (2003) 88,109–116.Google Scholar
Tomas, E, Tsao, TS, Saha, AK,Murrey, HE,Zhang, CC,Itani, SI,Lodish, HF & Ruderman, NBEnhanced muscle fat oxidation and glucose transport by ACRP30 globular domain: acetyl-CoA carboxylase inhibition and AMP-activated protein kinase activation. Proc Natl Acad Sci U S A (2002) 99,16309–16313.Google Scholar
Tomasetto, C, Karam, SM, Ribieras, S,Masson, R,Lefebvre, O,Staub, A,Alexander, G,Chenard, MP & Rio, MCIdentification and characterization of a novel gastric peptide hormone: the motilin-related peptide. Gastroenterology (2000) 119,395–405.Google Scholar
Toshinai, K, Date, Y, Murakami, N,et al.. Ghrelin-induced food intake is mediated via the orexin pathway. Endocrinology (2003) 144,1506–1512.Google Scholar
Toshinai, K, Mondal, MS, Nakazato, M,Date, Y,Murakami, N,Kojima, M,Kangawa, K & Matsukura, sUpregulation of ghrelin expression in the stomach upon fasting, insulin-induced hypoglycemia, and leptin administration. Biochem Biophys Res Commun (2001) 281,281–1225.Google Scholar
Tschop, M, Flora, DB, Mayer, JP & Heiman, MLHypophysectomy prevents ghrelin-induced adiposity and increases gastric ghrelin secretion in rats. Obes Res (2002) 10,991–999.Google Scholar
Tschop, M, Smiley, DL & Heiman, MLGhrelin induces adiposity in rodents. Nature (2000) 407,908–913.Google Scholar
Tschop, M, Wawarta, R, Riepl, RL,Friedrich, S,Bidlingmaier, M,Landgraf, R & Folwaczny, cPost-prandial decrease of circulating human ghrelin levels. J Endocrinol Invest (2001) 24,RC19–RC21.Google Scholar
Turnley, AM, Stapleton, D, Mann, RJ,Witters, LA,Kemp, BE & Bartlett, PFCellular distribution and developmental expression of AMP-activated protein kinase isoforms in mouse central nervous system. J Neurochem (1999) 72,1707–1716.Google Scholar
Ukkola, O, Ravussin, E, Jacobson, P,Snyder, EE,Chagnon, M,Sjostrom, L & Bouchard, cMutations in the preproghrelin/ghrelin gene associated with obesity in humans. J Clin Endocrinol Metab (2001) 86,3996–3999.Google Scholar
van der Lely, AJ, Tschop, M, Heiman, ML & Ghigo, EBiological, physiological, pathophysiological, and pharmacological aspects of ghrelin. Endocr Rev (2004) 25,426–457.Google Scholar
Viollet, B, Andreelli, F, Jorgensen, SB,et al.. The AMPactivated protein kinase alpha2 catalytic subunit controls whole-body insulin sensitivity. J Clin Invest (2003) 111,91–98.Google Scholar
Vivenza, D, Rapa, A, Castellino, N,Bellone, S,Petri, A,Vacca, G,Aimaretti, G,Broglio, F & Bona, GGhrelin gene polymorphisms and ghrelin, insulin, IGF-I, leptin and anthropometric data in children and adolescents. Eur J Endocrinol (2004) 151,127–133.Google Scholar
Wajnrajch, MP, Ten, IS, Gertner, JM & Leibel, RLGenomic organization of the ghrelin gene. J Endo Gen (2000) 1,231–233.Google Scholar
Wang, L, Saint-Pierre, DH & Tache, YPeripheral ghrelin selectively increases Fos expression in neuropeptide Y-synthesizing neurons in mouse hypothalamic arcuate nucleus. Neurosci Lett (2002) 325,47–51.Google Scholar
Watson, SJ, Akil, H, Richard, CW III & Barchas, JDEvidence for two separate opiate peptide neuronal systems. Nature (1978) 275,226–228.Google Scholar
Weber, E, Esch, FS, Bohlen, P,Paterson, S,Corbett, AD,McKnight, AT,Kosterlitz, HW,Barchas, JD & Evans, CJMetorphamide:isolation, structure, and biologic activity of an amidated opioid octapeptide from bovine brain. Proc Natl Acad Sci U S A (1983) 80,7362–7366.Google Scholar
Wierup, N, Yang, S, McEvilly, RJ,Mulder, H & Sundler, FGhrelin is expressed in a novel endocrine cell type in developing rat islets and inhibits insulin secretion from INS-1 (832/13) cells. J Histochem Cytochem (2004) 52,301–310.Google Scholar
Wiley, KE & Davenport, APComparison of vasodilators in human internal mammary artery: ghrelin is a potent physiological antagonist of endothelin-1. Br J Pharmacol (2002) 136,1146–1152.Google Scholar
Williams, J & Mobarhan, SA critical interaction: leptin and ghrelin. Nutr Rev (2003) 61,391–393.Google Scholar
Woods, SC, Stein, LJ, McKay, LD & Porte, D JrSuppression of food intake by intravenous nutrients and insulin in the baboon. Am J Physiol (1984) 247, R393–R401.Google Scholar
Wortley, KE, Anderson, KD, Garcia, K et al. . Genetic deletion of ghrelin does not decrease food intake but influences metabolic fuel preference Proc Natl Acad Sci U S A (2004) 101,8227–8232.Google Scholar
Wortley, KE, del Rincon, JP, Murray, JD,Garcia, K,Iida, K,Thorner, MO – Sleeman, MWAbsence of ghrelin protects against early-onset obesity. J Clin Invest (2005) 115,3573–3578.Google Scholar
Wren, AM, Seal, LJ, Cohen, MA, Brynes, AE, Frost, GS, Murphy, KG, Dhillo, WS,Ghatei, MA – Bloom, SRGhrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab (2001) 86, 5992–5995.Google Scholar
Yamanaka, AHypothalamic orexin neurons regulate arousal according to energy balance in mice Neuron (2003) 38 701–713Google Scholar
Yamauchi, T, Kamon, J & Minokoshi, Y et al. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase Nat Med (2002) 8 1288–1295Google Scholar
Yeh, AH, Jeffery, PL, Duncan, RP, Herington, AC, Chopin, LKGhrelin and a novel preproghrelin isoform are highly expressed in prostate cancer and ghrelin activates mitogen-activated protein kinase in prostate cancer. Clin Cancer Res (2005) 11, 8295–8303.Google Scholar
Yeh, LA, Lee, KH, Kim, KHRegulation of rat liver acetyl-CoA carboxylase. Regulation of phosphorylation and inactivation of acetyl CoA carboxylase by adenylate energy charge. J Biol Chem (1980) 255, 2308–2314.Google Scholar
Yildiz, BO, Suchard, MA, Wong, ML, McCann, SM, Licinio, JAlterations in the dynamics of circulating ghrelin, adiponectin, and leptin in human obesity. Proc Natl Acad Sci U S A (2004) 101, 10434–10439.Google Scholar
Yokota, I, Kitamura, S, Hosoda, H, Kotani, Y, Kangawa, KConcentration of the n-octanoylated active form of ghrelin in fetal and neonatal circulation. Endocr J (2005) 52, 271–276.Google Scholar
Zhang, JV, Ren, PG, Avsian-Kretchmer, O, Luo, CW, Rauch, R, Klein, C, Hsueh, AJObestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake. Science (2005) 310, 996–999.Google Scholar
Zigman, JM, Nakano, Y, Coppari, R et al. Mice lacking ghrelin receptors resist the development of diet-induced obesity. J Clin Invest (2005) 115, 3564–3572.Google Scholar
Zong, H, Ren, JM, Young, LH, Pypaert, M, Mu, J, Birnbaum, MJ, Shulman, GIAMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation. Proc Natl Acad Sci U S A (2002) 99, 15983–15987.Google Scholar
You have
Access
- 132
- Cited by