Focus on the short- and long-term effects of ghrelin on energy homeostasis

Nutrition

Volumn 26, Issue 6, 2010, Pages 579-584

  De Vriese, Carine ^a   Perret, Jason ^a   Delporte, Christine ^a  

^a UNIVERSITÉ LIBRE DE BRUXELLES   (Belgium)

Author keywords

Appetite regulation; Energy homeostasis; Ghrelin; Metabolism

Indexed keywords

ACYLTRANSFERASE; ANTIOBESITY AGENT; ANTISENSE OLIGONUCLEOTIDE; GHRELIN; GHRELIN O ACYLTRANSFERASE; GHRELIN RECEPTOR; GHRELIN RECEPTOR ANTAGONIST; GROWTH HORMONE SECRETAGOGUE RECEPTOR; NEUTRALIZING ANTIBODY; NOX B11 3; SPIEGELMER; UNCLASSIFIED DRUG;

ANOREXIA NERVOSA; ANTIBODY PRODUCTION; APPETITE; BODY WEIGHT; CACHEXIA; DOPAMINERGIC SYSTEM; DRUG BINDING; ENERGY METABOLISM; FOOD INTAKE; GENETIC POLYMORPHISM; HORMONE ACTION; HUMAN; MALNUTRITION; NONHUMAN; OBESITY; PRIORITY JOURNAL; REGULATORY MECHANISM; REVIEW; VACCINATION; WEIGHT GAIN; ANIMAL; CALORIC INTAKE; GENETICS; HOMEOSTASIS; METABOLISM; PATHOPHYSIOLOGY;

ANIMALS; APPETITE REGULATION; BODY WEIGHT; CACHEXIA; ENERGY INTAKE; ENERGY METABOLISM; GHRELIN; HOMEOSTASIS; HUMANS; OBESITY; POLYMORPHISM, GENETIC; RECEPTORS, GHRELIN;

EID: 77952742107     PISSN: 08999007     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.nut.2009.09.013     Document Type: Review

References (136)

1. Kojima M., Hosoda H., Date Y., Nakazato M., Matsuo H., Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 1999, 402:656-660.
2. Gutierrez J.A., Solenberg P.J., Perkins D.R., Willency J.A., Knierman M.D., Jin Z., et al. Ghrelin octanoylation mediated by an orphan lipid transferase 5. Proc Natl Acad Sci U S A 2008, 105:6320-6325.
3. Yang J., Brown M.S., Liang G., Grishin N.V., Goldstein J.L. Identification of the acyltransferase that octanoylates ghrelin, an appetite-stimulating peptide hormone. Cell 2008, 132:387-396.
4. Howard A.D., Feighner S.D., Cully D.F., Arena J.P., Liberator P.A., Rosenblum C.I., et al. A receptor in pituitary and hypothalamus that functions in growth hormone release. Science 1996, 273:974-977.
5. De Vriese C., Delporte C. Autocrine proliferative effect of ghrelin on leukemic HL-60 and THP-1 cells. J Endocrinol 2007, 192:199-205.
6. De Vriese C., Gregoire F., De Neef P., Robberecht P., Delporte C. Ghrelin is produced by the human erythroleukemic HEL cell line and involved in an autocrine pathway leading to cell proliferation. Endocrinology 2005, 146:1514-1522.
7. Ghigo E., Broglio F., Arvat E., Maccario M., Papotti M., Muccioli G. Ghrelin: more than a natural GH secretagogue and/or an orexigenic factor. Clin Endocrinol (Oxf) 2005, 62:1-17.
8. De Vriese C., Hacquebard M., Gregoire F., Carpentier Y., Delporte C. Ghrelin interacts with human plasma lipoproteins. Endocrinology 2007, 148:2355-2362.
9. Beaumont N.J., Skinner V.O., Tan T.M., Ramesh B.S., Byrne D.J., MacColl G.S., et al. Ghrelin can bind to a species of high density lipoprotein associated with paraoxonase. J Biol Chem 2003, 278:8877-8880.
10. Patterson M., Murphy K.G., le Roux C.W., Ghatei M.A., Bloom S.R. Characterization of ghrelin-like immunoreactivity in human plasma. J Clin Endocrinol Metab 2005, 90:2205-2211.
11. Akamizu T., Shinomiya T., Irako T., Fukunaga M., Nakai Y., Nakai Y., Kangawa K. Separate measurement of plasma levels of acylated and desacyl ghrelin in healthy subjects using a new direct ELISA assay. J Clin Endocrinol Metab 2005, 90:6-9.
12. De Vriese C., Gregoire F., Lema-Kisoka R., Waelbroeck M., Robberecht P., Delporte C. Ghrelin degradation by serum and tissue homogenates: identification of the cleavage sites. Endocrinology 2004, 145:4997-5005.
13. Takaya K., Ariyasu H., Kanamoto N., Iwakura H., Yoshimoto A., Harada M., et al. Ghrelin strongly stimulates growth hormone release in humans. J Clin Endocrinol Metab 2000, 85:4908-4911.
14. Date Y., Murakami N., Kojima M., Kuroiwa T., Matsukura S., Kangawa K., Nakazato M. Central effects of a novel acylated peptide, ghrelin, on growth hormone release in rats. Biochem Biophys Res Commun 2000, 275:477-480.
15. De Vriese C., Delporte C. Ghrelin: a new peptide regulating growth hormone release and food intake. Int J Biochem Cell Biol 2008, 40:1420-1424.
16. Soares J.B., Leite-Moreira A.F. Ghrelin, des-acyl ghrelin and obestatin: three pieces of the same puzzle. Peptides 2008, 29:1255-1270.
17. Nakazato M., Murakami N., Date Y., Kojima M., Matsuo H., Kangawa K., Matsukura S. A role for ghrelin in the central regulation of feeding. Nature 2001, 409:194-198.
18. Wren A.M., Seal L.J., Cohen M.A., Brynes A.E., Frost G.S., Murphy K.G., et al. Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab 2001, 86:5992-5995.
19. Cummings D.E., Purnell J.Q., Frayo R.S., Schmidova K., Wisse B.E., Weigle D.S. A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes 2001, 50:1714-1719.
20. Cummings D.E., Frayo R.S., Marmonier C., Aubert R., Chapelot D. Plasma ghrelin levels and hunger scores in humans initiating meals voluntarily without time- and food-related cues. Am J Physiol Endocrinol Metab 2004, 287:E297-E304.
21. Frecka J.M., Mattes R.D. Possible entrainment of ghrelin to habitual meal patterns in humans. Am J Physiol Gastrointest Liver Physiol 2008, 294:G699-G707.
22. Drazen D.L., Vahl T.P., D'Alessio D.A., Seeley R.J., Woods S.C. Effects of a fixed meal pattern on ghrelin secretion: evidence for a learned response independent of nutrient status. Endocrinology 2006, 147:23-30.
23. Overduin J., Frayo R.S., Grill H.J., Kaplan J.M., Cummings D.E. Role of the duodenum and macronutrient type in ghrelin regulation. Endocrinology 2005, 146:845-850.
24. Foster-Schubert K.E., Overduin J., Prudom C.E., Liu J., Callahan H.S., Gaylinn B.D. e al. Acyl and total ghrelin are suppressed strongly by ingested proteins, weakly by lipids, and biphasically by carbohydrates. J Clin Endocrinol Metab 2008, 93:1971-1979.
25. Beck B., Richy S. Differential long-term dietary regulation of adipokines, ghrelin, or corticosterone: impact on adiposity. J Endocrinol 2008, 196:171-179.
26. Beck B., Max J.P., Fernette B., Richy S. Adaptation of ghrelin levels to limit body weight gain in the obese Zucker rat. Biochem Biophys Res Commun 2004, 318:846-851.
27. Blom W.A., de Graaf C., Lluch A., Stafleu A., Schaafsma G., Hendriks H.F. Postprandial ghrelin responses are associated with the intermeal interval in time-blinded normal weight men, but not in obese men. Physiol Behav 2009, 96:742-748.
28. Huda M.S.B., Wilding J.P.H., Pinkney J.H. Gut peptides and the regulation of appetite. Obes Rev 2006, 7:163-182.
29. Abizaid A., Horvath T.L. Brain circuits regulating energy homeostasis. Regul Pept 2008, 149:3-10.
30. Shioda S., Takenoya F., Yagi M., Wang L., Hori Y., Kageyama H. Neural networks of several novel neuropeptides involved in feeding regulation. Nutrition 2008, 24:848-853.
31. Chen H.Y., Trumbauer M.E., Chen A.S., Weingarth D.T., Adams J.R., Frazier E.G., et al. Orexigenic action of peripheral ghrelin is mediated by neuropeptide Y and agouti-related protein. Endocrinology 2004, 145:2607-2612.
32. Coiro V., Saccani-Jotti G., Rubino P., Manfredi G., Melani A., Chiodera P. Effects of ghrelin on circulating neuropeptide Y levels in humans. Neurol Endocrinol Lett 2006, 27:755-757.
33. Luquet S., Phillips C.T., Palmiter R.D. NPY/AgRP neurons are not essential for feeding responses to glucoprivation. Peptides 2007, 28:214-225.
34. Kola B., Hubina E., Tucci S.A., Kirkham T.C., Garcia E.A., Mitchell S.E., et al. Cannabinoids and ghrelin have both central and peripheral metabolic and cardiac effects via AMP-activated protein kinase. J Biol Chem 2005, 280:25196-25201.
35. Kola B., Korbonits M. Shedding light on the intricate puzzle of ghrelin's effects on appetite regulation. J Endocrinol 2009, 202:191-198.
36. Anderson K.A., Ribar T.J., Lin F., Noeldner P.K., Green M.F., Muehlbauer M.J., et al. Hypothalamic CaMKK2 contributes to the regulation of energy balance. Cell Metab 2008, 7:377-388.
37. Lopez M., Lage R., Saha A.K., Perez-Tilve D., Vazquez M.J., Varela L., et al. Hypothalamic fatty acid metabolism mediates the orexigenic action of ghrelin. Cell Metab 2008, 7:389-399.
38. Andrews Z.B., Liu Z.W., Walllingford N., Erion D.M., Borok E., Friedman J.M., et al. UCP2 mediates ghrelin's action on NPY/AgRP neurons by lowering free radicals. Nature 2008, 454:846-851.
39. Kola B., Farkas I., Christ-Crain M., Wittmann G., Lolli F., Amin F., et al. The orexigenic effect of ghrelin is mediated through central activation of the endogenous cannabinoid system. PLoS One 2008, 3:e1797.
40. Riediger T., Traebert M., Schmid H.A., Scheel C., Lutz T.A., Scharrer E. Site-specific effects of ghrelin on the neuronal activity in the hypothalamic arcuate nucleus. Neurosci Lett 2003, 341:151-155.
41. Scott V., Mcdade D.M., Luckman S.M. Rapid changes in the sensitivity of arcuate nucleus neurons to central ghrelin in relation to feeding status. Physiol Behav 2007, 90:180-185.
42. Yamanaka A., Beuckmann C.T., Willie J.T., Hara J., Tsujino N., Mieda M., et al. Hypothalamic orexin neurons regulate arousal according to energy balance in mice. Neuron 2003, 38:701-713.
43. Toshinai K., Date Y., Murakami N., Shimada M., Mondal M.S., Shimbara T., et al. Ghrelin-induced food intake is mediated via the orexin pathway. Endocrinology 2003, 144:1506-1512.
44. Jerlhag E. Systemic administration of ghrelin induces conditioned place preference and stimulates accumbal dopamine. Addict Biol 2008, 13:358-363.
45. Naleid A.M., Grace M.K., Cummings D.E., Levine A.S. Ghrelin induces feeding in the mesolimbic reward pathway between the ventral tegmental area and the nucleus accumbens. Peptides 2005, 26:2274-2279.
46. Jerlhag E., Egecioglu E., Dickson S.L., Douhan A., Svensson L., Engel J.A. Ghrelin administration into tegmental areas stimulates locomotor activity and increases extracellular concentration of dopamine in the nucleus accumbens. Addict Biol 2007, 12:6-16.
47. Abizaid A. Ghrelin and dopamine: new insights on the peripheral regulation of appetite. J Neuroendocrinol 2009, 21:787-793.
48. Malik S., McGlone F., Bedrossian D., Dagher A. Ghrelin modulates brain activity in areas that control appetitive behavior. Cell Metab 2008, 7:400-409.
49. Sakata I., Yamazaki M., Inoue K., Hayashi Y., Kangawa K., Sakai T. Growth hormone secretagogue receptor expression in the cells of the stomach-projected afferent nerve in the rat nodose ganglion. Neurosci Lett 2003, 342:183-186.
50. Burdyga G., Varro A., Dimaline R., Thompson D.G., Dockray G.J. Ghrelin receptors in rat and human nodose ganglia: putative role in regulating CB-1 and MCH receptor abundance. Am J Physiol Gastrointest Liver Physiol 2006, 290:G1289-G1297.
51. Date Y., Murakami N., Toshinai K., Matsukura S., Niijima A., Matsuo H., et al. The role of the gastric afferent vagal nerve in ghrelin-induced feeding and growth hormone secretion in rats. Gastroenterology 2002, 123:1120-1128.
52. Arnold M., Mura A., Langhans W., Geary N. Gut vagal afferents are not necessary for the eating-stimulatory effect of intraperitoneally injected ghrelin in the rat. J Neurosci 2006, 26:11052-11060.
53. Date Y., Murakami N., Toshinai K., Matsukura S., Niijima A., Matsuo H., et al. The role of the gastric afferent vagal nerve in ghrelin-induced feeding and growth hormone secretion in rats. Gastroenterology 2002, 123:1120-1128.
54. le Roux C.W., Neary N.M., Halsey T.J., Small C.J., Martinez-Isla A.M., Ghatei M.A., et al. Ghrelin does not stimulate food intake in patients with surgical procedures involving vagotomy. J Clin Endocrinol Metab 2005, 90:4521-4524.
55. Date Y., Shimbara T., Koda S., Toshinai K., Ida T., Murakami N., et al. Peripheral ghrelin transmits orexigenic signals through the noradrenergic pathway from the hindbrain to the hypothalamus. Cell Metab 2006, 4:323-331.
56. Maier C., Riedl M., Vila G., Nowotny P., Wolzt M., Clodi M., et al. Cholinergic regulation of ghrelin and peptide YY release may be impaired in obesity. Diabetes 2008, 57:2332-2340.
57. Tschop M., Smiley D.L., Heiman M.L. Ghrelin induces adiposity in rodents. Nature 2000, 407:908-913.
58. Tsubone T., Masaki T., Katsuragi I., Tanaka K., Kakuma T., Yoshimatsu H. Ghrelin regulates adiposity in white adipose tissue and UCP1 mRNA expression in brown adipose tissue in mice. Regul Pept 2005, 130:97-103.
59. Wortley K.E., Anderson K.D., Garcia K., Murray J.D., Malinova L., Liu R., 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.
60. Pfluger P.T., Kirchner H., Gunnel S., Schrott B., Perez-Tilve D., Fu S., et al. Simultaneous deletion of ghrelin and its receptor increases motor activity and energy expenditure. Am J Physiol Gastrointest Liver Physiol 2008, 294:G610-G618.
61. Thompson N.M., Gill D.A., Davies R., Loveridge N., Houston P.A., Robinson I.C., Wells T. Ghrelin 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.
62. Kim S.W., Her S.J., Park S.J., Kim D., Park K.S., Lee H.K., et al. Ghrelin stimulates proliferation and differentiation and inhibits apoptosis in osteoblastic MC3T3-E1 cells. Bone 2005, 37:359-369.
63. Shimbara T., Mondal M.S., Kawagoe T., Toshinai K., Koda S., Yamaguchi H., et al. Central administration of ghrelin preferentially enhances fat ingestion. Neurosci Lett 2004, 369:75-79.
64. Soriano-Guillen L., Barrios V., Campos-Barros A., Argente J. Ghrelin levels in obesity and anorexia nervosa: effect of weight reduction or recuperation. J Pediatr 2004, 144:36-42.
65. Purnell J.Q., Cummings D., Weigle D.S. Changes in 24-h area-under-the-curve ghrelin values following diet-induced weight loss are associated with loss of fat-free mass, but not with changes in fat mass, insulin levels or insulin sensitivity. Int J Obes (Lond) 2007, 31:385-389.
66. Nagaya N., Uematsu M., Kojima M., Date Y., Nakazato M., Okumura H., et al. Elevated circulating level of ghrelin in cachexia associated with chronic heart failure: relationships between ghrelin and anabolic/catabolic factors. Circulation 2001, 104:2034-2038.
67. Cummings D.E., Weigle D.S., Frayo R.S., Breen P.A., Ma M.K., Dellinger E.P., Purnell J.Q. Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med 2002, 346:1623-1630.
68. De Vriese C., Delporte C. Influence of ghrelin on food intake and energy homeostasis. Curr Opin Clin Nutr Metab Care 2007, 10:615-619.
69. Shiiya T., Nakazato M., Mizuta M., Date Y., Mondal M.S., Tanaka M., et al. Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion. J Clin Endocrinol Metab 2002, 87:240-244.
70. Purnell J.Q., Cummings D., Weigle D.S. Changes in 24-h area-under-the-curve ghrelin values following diet-induced weight loss are associated with loss of fat-free mass, but not with changes in fat mass, insulin levels or insulin sensitivity. Int J Obes (Lond) 2007, 31:385-389.
71. Kraemer R.R., Castracane V.D. Exercise and humoral mediators of peripheral energy balance: ghrelin and adiponectin. Exp Biol Med (Maywood) 2007, 232:184-194.
72. Beck B., Richy S. Dietary modulation of ghrelin and leptin and gorging behavior after weight loss in the obese Zucker rat. J Endocrinol 2009, 202:29-34.
73. Stratis C., Alexandrides T., Vagenas K., Kalfarentzos F. Ghrelin and peptide YY levels after a variant of biliopancreatic diversion with Roux-en-Y gastric bypass versus after colectomy: a prospective comparative study. Obes Surg 2006, 16:752-758.
74. Mingrone G., Granato L., Valera-Mora E., Iaconelli A., Calvani M.F., Bracaglia R., et al. Ultradian ghrelin pulsatility is disrupted in morbidly obese subjects after weight loss induced by malabsorptive bariatric surgery. Am J Clin Nutr 2006, 83:1017-1024.
75. Holdstock C., Engstrom B.E., Ohrvall M., Lind L., Sundbom M., Karlsson F.A. Ghrelin and adipose tissue regulatory peptides: effect of gastric bypass surgery in obese humans. J Clin Endocrinol Metab 2003, 88:3177-3183.
76. Fruhbeck G., Rotellar F., Hernandez-Lizoain J.L., Gil M.J., Gomez-Ambrosi J., Salvador J., Cienfuegos J.A. Fasting plasma ghrelin concentrations 6 months after gastric bypass are not determined by weight loss or changes in insulinemia. Obes Surg 2004, 14:1208-1215.
77. Langer F.B., Reza Hoda M.A., Bohdjalian A., Felberbauer F.X., Zacherl J., Wenzl E., et al. Sleeve gastrectomy and gastric banding: effects on plasma ghrelin levels. Obes Surg 2005, 15:1024-1029.
78. Roth C.L., Reinehr T., Schernthaner G.H., Kopp H.P., Kriwanek S., Schernthaner G. Ghrelin and obestatin levels in severely obese women before and after weight loss after Roux-en-Y gastric bypass surgery. Obes Surg 2009, 19:29-35.
79. Stenstrom B., Zhao C.M., Tommeras K., Arum C.J., Chen D. Is gastrin partially responsible for body weight reduction after gastric bypass?. Eur Surg Res 2006, 38:94-101.
80. Mancini M.C., Costa A.P., de Melo M.E., Cercato C., Giannella-Neto D., Garrido A.B., et al. Effect of gastric bypass on spontaneous growth hormone and ghrelin release profiles. Obesity (Silver Spring) 2006, 14:383-387.
81. Olivan B., Teixeira J., Bose M., Bawa B., Chang T., Summe H., et al. Effect of weight loss by diet or gastric bypass surgery on peptide YY3-36 levels. Ann Surg 2009, 249:948-953.
82. Ybarra J., Bobbioni-Harsch E., Chassot G., Huber O., Morel P., Assimacopoulos-Jeannet F., Golay A. Persistent correlation of ghrelin plasma levels with body mass index both in stable weight conditions and during gastric-bypass-induced weight loss. Obes Surg 2009, 19:327-331.
83. Williams D.L., Grill H.J., Cummings D.E., Kaplan J.M. Overfeeding-induced weight gain suppresses plasma ghrelin levels in rats. J Endocrinol Invest 2006, 29:863-868.
84. Palik E., Baranyi E., Melczer Z., Audikovszky M., Szocs A., Winkler G., Cseh K. Elevated serum acylated (biologically active) ghrelin and resistin levels associate with pregnancy-induced weight gain and insulin resistance. Diabetes Res Clin Pract 2007, 76:351-357.
85. Hosojima H., Togo T., Odawara T., Hasegawa K., Miura S., Kato Y., et al. Early effects of olanzapine on serum levels of ghrelin, adiponectin and leptin in patients with schizophrenia. J Psychopharmacol 2006, 20:75-79.
86. Otukonyong E.E., Dube M.G., Torto R., Kalra P.S., Kalra S.P. High-fat diet-induced ultradian leptin and insulin hypersecretion are absent in obesity-resistant rats. Obes Res 2005, 13:991-999.
87. Kim B.J., Sohn J.W., Park C.S., Hahn G.H., Koo J., Noh Y.D., Lee C.S. Body weight and plasma levels of ghrelin and leptin during treatment with olanzapine. J Korean Med Sci 2008, 23:685-690.
88. Perez-Iglesias R., Vazquez-Barquero J.L., Amado J.A., Berja A., Garcia-Unzueta M.T., Pelayo-Teran J.M., et al. Effect of antipsychotics on peptides involved in energy balance in drug-naive psychotic patients after 1 year of treatment. J Clin Psychopharmacol 2008, 28:289-295.
89. Cummings D.E., Clement K., Purnell J.Q., Vaisse C., Foster K.E., Frayo R.S., et al. Elevated plasma ghrelin levels in Prader Willi syndrome. Nat Med 2002, 8:643-644.
90. DelParigi A., Tschop M., Heiman M.L., Salbe A.D., Vozarova B., Sell S.M., et al. High circulating ghrelin: a potential cause for hyperphagia and obesity in Prader-Willi syndrome. J Clin Endocrinol Metab 2002, 87:5461-5464.
91. Gimenez-Palop O., Gimenez-Perez G., Mauricio D., Gonzalez-Clemente J.M., Potau N., Berlanga E., et al. A lesser postprandial suppression of plasma ghrelin in Prader-Willi syndrome is associated with low fasting and a blunted postprandial PYY response. Clin Endocrinol (Oxf) 2007, 66:198-204.
92. Erdie-Lalena C.R., Holm V.A., Kelly P.C., Frayo R.S., Cummings D.E. Ghrelin levels in young children with Prader-Willi syndrome. J Pediatr 2006, 149:199-204.
93. Haqq A.M., Farooqi I.S., O'Rahilly S., Stadler D.D., Rosenfeld R.G., Pratt K.L., et al. Serum 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, 88:174-178.
94. Haqq A.M., Grambow S.C., Muehlbauer M., Newgard C.B., Svetkey L.P., Carrel A.L., et al. Ghrelin concentrations in Prader-Willi syndrome (PWS) infants and children: changes during development. Clin Endocrinol (Oxf) 2008, 69:911-920.
95. Seim I., Carter S.L., Herington A.C., Chopin L.K. Complex organisation and structure of the ghrelin antisense strand gene GHRLOS, a candidate non-coding RNA gene. BMC Mol Biol 2008, 9:95.
96. Seim I., Herington A.C., Chopin L.K. New insights into the molecular complexity of the ghrelin gene locus. Cytokine Growth Factor Rev 2009, 20:297-304.
97. Seim I., Amorim L., Walpole C., Carter S., Chopin L.K., Herington A.C. Ghrelin gene-related peptides: multi-functional endocrine/autocrine modulators in health and disease. Clin Exp Pharmacol Physiol 2009, Epub ahead of print.
98. Soares J.B., Leite-Moreira A.F. Ghrelin, des-acyl ghrelin and obestatin: three pieces of the same puzzle 2. Peptides 2008, 29:1255-1270.
99. Zhang J.V., Ren P.G., Avsian-Kretchmer O., Luo C.W., Rauch R., Klein C., Hsueh A.J. Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake. Science 2005, 310:996-999.
100. Dossus L., McKay J.D., Canzian F., Wilkening S., Rinaldi S., Biessy C., et al. Polymorphisms of genes coding for ghrelin and its receptor in relation to anthropometry, circulating levels of IGF-I and IGFBP-3, and breast cancer risk: a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). Carcinogenesis 2008, 29:1360-1366.
101. Jeffery P.L., Murray R.E., Yeh A.H., McNamara J.F., Duncan R.P., Francis G.D., et al. Expression and function of the ghrelin axis, including a novel preproghrelin isoform, in human breast cancer tissues and cell lines. Endocr Relat Cancer 2005, 12:839-850.
102. Yeh A.H., Jeffery P.L., Duncan R.P., Herington A.C., Chopin L.K. Ghrelin 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.
103. Korbonits M., Gueorguiev M., O'Grady E., Lecoeur C., Swan D.C., Mein C.A., et al. A variation in the ghrelin gene increases weight and decreases insulin secretion in tall, obese children. J Clin Endocrinol Metab 2002, 87:4005-4008.
104. Miraglia dGSantoro N., Cirillo G., Raimondo P., Grandone A., D'Aniello A., et al. Molecular screening of the ghrelin gene in Italian obese children: the Leu72Met variant is associated with an earlier onset of obesity. Int J Obes Relat Metab Disord 2004, 28:447-450.
105. Ukkola O., Ravussin E., Jacobson P., Snyder E.E., Chagnon M., Sjostrom L., Bouchard C. Mutations in the preproghrelin/ghrelin gene associated with obesity in humans. J Clin Endocrinol Metab 2001, 86:3996-3999.
106. Ukkola O., Ravussin E., Jacobson P., Perusse L., Rankinen T., Tschop M., et al. Role of ghrelin polymorphisms in obesity based on three different studies. Obes Res 2002, 10:782-791.
107. Monteleone P., Tortorella A., Castaldo E., Di Filippo C., Maj M. The Leu72Met polymorphism of the ghrelin gene is significantly associated with binge eating disorder. Psychiatr Genet 2007, 17:13-16.
108. Monteleone P., Tortorella A., Castaldo E., Di Filippo C., Maj M. No association of the Arg51Gln and Leu72Met polymorphisms of the ghrelin gene with anorexia nervosa or bulimia nervosa. Neurosci Lett 2006, 398:325-327.
109. Dardennes R.M., Zizzari P., Tolle V., Foulon C., Kipman A., Romo L., et al. Family trios analysis of common polymorphisms in the obestatin/ghrelin, BDNF and AGRP genes in patients with anorexia nervosa: association with subtype, body-mass index, severity and age of onset. Psychoneuroendocrinology 2007, 32:106-113.
110. Ying B.W., Song X.B., Fan H., Wang L.L., Li Y.S., Cheng Z., et al. Plasma ghrelin levels and weight loss in Chinese Uygur patients with chronic obstructive pulmonary disease. J Int Med Res 2008, 36:1371-1377.
111. Otto B., Cuntz U., Fruehauf E., Wawarta R., Folwaczny C., Riepl R.L., et al. Weight gain decreases elevated plasma ghrelin concentrations of patients with anorexia nervosa. Eur J Endocrinol 2001, 145:669-673.
112. Neary N.M., Small C.J., Wren A.M., Lee J.L., Druce M.R., Palmieri C., et al. Ghrelin increases energy intake in cancer patients with impaired appetite: acute, randomized, placebo-controlled trial. J Clin Endocrinol Metab 2004, 89:2832-2836.
113. Wynne K., Giannitsopoulou K., Small C.J., Patterson M., Frost G., Ghatei M.A., et al. Subcutaneous ghrelin enhances acute food intake in malnourished patients who receive maintenance peritoneal dialysis: a randomized, placebo-controlled trial. J Am Soc Nephrol 2005, 16:2111-2118.
114. Ashby D.R., Ford H.E., Wynne K.J., Wren A.M., Murphy K.G., Busbridge M., et al. Sustained appetite improvement in malnourished dialysis patients by daily ghrelin treatment. Kidney Int 2009, 76:199-206.
115. Nagaya N., Kojima M., Kangawa K. Ghrelin, a novel growth hormone-releasing peptide, in the treatment of cardiopulmonary-associated cachexia. Intern Med 2006, 45:127-134.
116. Nagaya N., Moriya J., Yasumura Y., Uematsu M., Ono F., Shimizu W., et al. Effects of ghrelin administration on left ventricular function, exercise capacity, and muscle wasting in patients with chronic heart failure. Circulation 2004, 110:3674-3679.
117. Nagaya N., Itoh T., Murakami S., Oya H., Uematsu M., Miyatake K., Kangawa K. Treatment of cachexia with ghrelin in patients with COPD. Chest 2005, 128:1187-1193.
118. Strassburg S., Anker S.D., Castaneda T.R., Burget L., Perez-Tilve D., Pfluger P.T., et al. Long-term effects of ghrelin and ghrelin receptor agonists on energy balance in rats. Am J Physiol Endocrinol Metab 2008, 295:E78-E84.
119. Garcia J.M., Polvino W.J. Pharmacodynamic hormonal effects of anamorelin, a novel oral ghrelin mimetic and growth hormone secretagogue in healthy volunteers. Growth Horm IGF Res 2009, 19:267-273.
120. Garcia J.M., Polvino W.J. Effect on body weight and safety of RC-1291, a novel, orally available ghrelin mimetic and growth hormone secretagogue: results of a phase I, randomized, placebo-controlled, multiple-dose study in healthy volunteers. Oncologist 2007, 12:594-600.
121. Asakawa A., Inui A., Kaga T., Katsuura G., Fujimiya M., Fujino M.A., Kasuga M. Antagonism of ghrelin receptor reduces food intake and body weight gain in mice. Gut 2003, 52:947-952.
122. Beck B., Richy S., Stricker-Krongrad A. Feeding response to ghrelin agonist and antagonist in lean and obese Zucker rats. Life Sci 2004, 76:473-478.
123. Esler W.P., Rudolph J., Claus T.H., Tang W., Barucci N., Brown S.E., et al. Small-molecule ghrelin receptor antagonists improve glucose tolerance, suppress appetite, and promote weight loss. Endocrinology 2007, 148:5175-5185.
124. Rudolph J., Esler W.P., O'Connor S., Coish P.D., Wickens P.L., Brands M., et al. Quinazolinone derivatives as orally available ghrelin receptor antagonists for the treatment of diabetes and obesity. J Med Chem 2007, 50:5202-5216.
125. Holst B., Cygankiewicz A., Jensen T.H., Ankersen M., Schwartz T.W. High constitutive signaling of the ghrelin receptor-identification of a potent inverse agonist. Mol Endocrinol 2003, 17:2201-2210.
126. Holst B., Schwartz T.W. Constitutive ghrelin receptor activity as a signaling set-point in appetite regulation. Trends Pharmacol Sci 2004, 25:113-117.
127. Holst B., Lang M., Brandt E., Bach A., Howard A., Frimurer T.M., et al. Ghrelin receptor inverse agonists: identification of an active peptide core and its interaction epitopes on the receptor. Mol Pharmacol 2006, 70:936-946.
128. Wang H.J., Geller F., Dempfle A., Schauble N., Friedel S., Lichtner P., et al. Ghrelin receptor gene: identification of several sequence variants in extremely obese children and adolescents, healthy normal-weight and underweight students, and children with short normal stature. J Clin Endocrinol Metab 2004, 89:157-162.
129. Pantel J., Legendre M., Cabrol S., Hilal L., Hajaji Y., Morisset S., et al. Loss of constitutive activity of the growth hormone secretagogue receptor in familial short stature. J Clin Invest 2006, 116:760-768.
130. Kobelt P., Helmling S., Stengel A., Wlotzka B., Andresen V., Klapp B.F., et al. Anti-ghrelin Spiegelmer NOX-B11 inhibits neurostimulatory and orexigenic effects of peripheral ghrelin in rats. Gut 2006, 55:788-792.
131. Shearman L.P., Wang S.P., Helmling S., Stribling D.S., Mazur P., Ge L., et al. Ghrelin neutralization by a ribonucleic acid-SPM ameliorates obesity in diet-induced obese mice. Endocrinology 2006, 147:1517-1526.
132. Helmling S., Maasch C., Eulberg D., Buchner K., Schroder W., Lange C., et al. Inhibition of ghrelin action in vitro and in vivo by an RNA-Spiegelmer. Proc Natl Acad Sci U S A 2004, 101:13174-13179.
133. Becskei C., Bilik K.U., Klussmann S., Jarosch F., Lutz T.A., Riediger T. The anti-ghrelin Spiegelmer NOX-B11-3 blocks ghrelin- but not fasting-induced neuronal activation in the hypothalamic arcuate nucleus. J Neuroendocrinol 2008, 20:85-92.
134. Zorrilla E.P., Iwasaki S., Moss J.A., Chang J., Otsuji J., Inoue K., et al. Vaccination against weight gain. Proc Natl Acad Sci U S A 2006, 103:13226-13231.
135. Lu S.C., Xu J., Chinookoswong N., Liu S., Steavenson S., Gegg C., et al. An acyl-ghrelin-specific neutralizing antibody inhibits the acute ghrelin-mediated orexigenic effects in mice. Mol Pharmacol 2009, 75:901-907.
136. Mayorov A.V., Amara N., Chang J.Y., Moss J.A., Hixon M.S., Ruiz D.I., et al. Catalytic antibody degradation of ghrelin increases whole-body metabolic rate and reduces refeeding in fasting mice. Proc Natl Acad Sci U S A 2008, 105:17487-17492.