Ghrelin and cachexia: Will treatment with GHSR-1a agonists make a difference for patients suffering from chronic wasting syndromes?

Molecular and Cellular Endocrinology

Volumn 340, Issue 1, 2011, Pages 97-105

  DeBoer, Mark D ^a  

^a UNIVERSITY OF VIRGINIA   (United States)

Author keywords

Anorexia; Cachexia; Cancer; Chronic heart failure; Chronic kidney disease; Ghrelin; Growth hormone secretegogue receptor; Inflammation; Melanocortin; Wasting

Indexed keywords

ANAMORELIN; GHRELIN; GHRELIN RECEPTOR AGONIST; GROWTH HORMONE; HORMONE RECEPTOR STIMULATING AGENT; PLACEBO; SOMATOMEDIN C; SUN 11031; UNCLASSIFIED DRUG;

ABDOMINAL PAIN; ANOREXIA; CACHEXIA; CANCER CACHEXIA; CHRONIC KIDNEY DISEASE CACHEXIA; CLINICAL TRIAL (TOPIC); DRUG EFFICACY; DRUG MEGADOSE; DRUG SAFETY; DRUG TOLERABILITY; ENERGY BALANCE; GASTROINTESTINAL SYMPTOM; HEART FAILURE; HORMONAL REGULATION; HORMONE ACTION; HORMONE RELEASE; HUMAN; KIDNEY CLEARANCE; LOW DRUG DOSE; NONHUMAN; PRIORITY JOURNAL; PULMONARY CACHEXIA; REVIEW; TREATMENT DURATION; TREATMENT RESPONSE; WEIGHT REDUCTION; XEROSTOMIA;

CACHEXIA; CHRONIC DISEASE; GHRELIN; HUMANS; MODELS, BIOLOGICAL; RECEPTORS, GHRELIN; WASTING SYNDROME;

EID: 79958134198     PISSN: 03037207     EISSN: 18728057     Source Type: Journal    
DOI: 10.1016/j.mce.2011.02.012     Document Type: Review

References (99)

1. Adachi S., Takiguchi S., Okada K., Yamamoto K., Yamasaki M., Miyata H., Nakajima K., Fujiwara Y., Hosoda H., Kangawa K., Mori M., Doki Y. Effects of ghrelin administration after total gastrectomy: a prospective, randomized, placebo-controlled phase II study. Gastroenterology 2010, 138::1312-1320.
2. Adey D., Kumar R., McCarthy J.T., Nair K.S. Reduced synthesis of muscle proteins in chronic renal failure. Am. J. Physiol. Endocrinol. Metab. 2000, 278::E219-225.
3. Akashi Y.J., Palus S., Datta R., Halem H., Taylor J.E., Thoene-Reineke C., Dong J., Thum T., Culler M.D., Anker S.D., Springer J. No effects of human ghrelin on cardiac function despite profound effects on body composition in a rat model of heart failure. Int. J. Cardiol. 2009, 137:267-275.
4. American_Heart_Association Heart Disease and Stroke Statistics 2005, American Heart Association Update, Dallas, TX
5. Andreas S., Anker S.D., Scanlon P.D., Somers V.K. Neurohumoral activation as a link to systemic manifestations of chronic lung disease. Chest 2005, 128:3618-3624.
6. Anker S.D., Ponikowski P., Varney S., Chua T.P., Clark A.L., Webb-Peploe K.M., Harrington D., Kox W.J., Poole-Wilson P.A., Coats A.J. Wasting as independent risk factor for mortality in chronic heart failure. Lancet 1997, 349:1050-1053.
7. Anker S.D., Swan J.W., Volterrani M., Chua T.P., Clark A.L., Poole-Wilson P.A., Coats A.J. The influence of muscle mass, strength, fatigability and blood flow on exercise capacity in cachectic and non-cachectic patients with chronic heart failure. Eur. Heart J. 1997, 18:259-269.
8. Ariyasu H., Takaya K., Iwakura H., Hosoda H., Akamizu T., Arai Y., Kangawa K., Nakao K. Transgenic mice overexpressing des-acyl ghrelin show small phenotype. Endocrinology 2005, 146:355-364.
9. Asakawa A., Inui A., Fujimiya M., Sakamaki R., Shinfuku N., Ueta Y., Meguid M.M., Kasuga M. Stomach regulates energy balance via acylated ghrelin and desacyl ghrelin. Gut 2005, 54:18-24.
10. Ashby D.R., Ford H.E., Wynne K.J., Wren A.M., Murphy K.G., Busbridge M., Brown E.A., Taube D.H., Ghatei M.A., Tam F.W., Bloom S.R., Choi P. Sustained appetite improvement in malnourished dialysis patients by daily ghrelin treatment. Kidney Int. 2009, 76:199-206.
11. Balasubramaniam A., Wood S., Joshi R., Su C., Friend L.A., Sheriff S., James J.H. Ghrelin stimulates food intake and growth hormone release in rats with thermal injury: synthesis of ghrelin. Peptides 2006, 27:1624-1631.
12. Barazzoni R., Zhu X., Deboer M., Datta R., Culler M.D., Zanetti M., Guarnieri G., Marks D.L. Combined effects of ghrelin and higher food intake enhance skeletal muscle mitochondrial oxidative capacity and AKT phosphorylation in rats with chronic kidney disease. Kidney Int. 2010, 77:23-28.
13. Barber M.D., Ross J.A., Fearon K.C. Changes in nutritional, functional, and inflammatory markers in advanced pancreatic cancer. Nutr. Cancer 1999, 35:106-110.
14. Binn M., Albert C., Gougeon A., Maerki H., Coulie B., Lemoyne M., Rabasa Lhoret R., Tomasetto C., Poitras P. Ghrelin gastrokinetic action in patients with neurogenic gastroparesis. Peptides 2006, 27:1603-1606.
15. Bossola M., Scribano D., Colacicco L., Tavazzi B., Giungi S., Zuppi C., Luciani G., Tazza L. Anorexia and plasma levels of free tryptophan, branched chain amino acids, and ghrelin in hemodialysis patients. J. Ren. Nutr. 2009, 19:248-255.
16. Brodt P., Samani A., Navab R. Inhibition of the type I insulin-like growth factor receptor expression and signaling: novel strategies for antimetastatic therapy. Biochem. Pharmacol. 2000, 60:1101-1107.
17. Buscher A.K., Buscher R., Hauffa B.P., Hoyer P.F. Alterations in appetite-regulating hormones influence protein-energy wasting in pediatric patients with chronic kidney disease. Pediatr. Nephrol. 2010, 25:2295-2301.
18. Chang L., Zhao J., Yang J., Zhang Z., Du J., Tang C. Therapeutic effects of ghrelin on endotoxic shock in rats. Eur. J. Pharmacol. 2003, 473:171-176.
19. Chen H.Y., Trumbauer M.E., Chen A.S., Weingarth D.T., Adams J.R., Frazier E.G., Shen Z., Marsh D.J., Feighner S.D., Guan X.M., Ye Z., Nargund R.P., Smith R.G., Van der Ploeg L.H., Howard A.D., MacNeil D.J., Qian S. Orexigenic action of peripheral ghrelin is mediated by neuropeptide Y and agouti-related protein. Endocrinology 2004, 145:2607-2612.
20. Cowley M.A., Smith R.G., Diano S., Tschop M., Pronchuk N., Grove K.L., Strasburger C.J., Bidlingmaier M., Esterman M., Heiman M.L., Garcia-Segura L.M., Nillni E.A., Mendez P., Low M.J., Sotonyi P., Friedman J.M., Liu H., Pinto S., Colmers W.F., Cone R.D., Horvath T.L. The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis. Neuron 2003, 37:649-661.
21. 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.
22. Deans C., Wigmore S.J. Systemic inflammation, cachexia and prognosis in patients with cancer. Curr. Opin. Clin. Nutr. Metab. Care 2005, 8:265-269.
23. DeBoer M.D. Emergence of ghrelin as a treatment for cachexia syndromes. Nutrition 2008, 24:806-814.
24. DeBoer M.D. Animal models of anorexia and cachexia. Expert Opin. Drug Discov. 2009, 4:1145-1155.
25. DeBoer M.D. Update on melanocortin interventions for cachexia: progress toward clinical application. Nutrition 2010, 26:146-151.
26. DeBoer M.D., Marks D.L. Therapy insight: use of melanocortin antagonists in the treatment of cachexia in chronic disease. Nat. Clin. Pract. Endocrinol. Metab. 2006, 2:459-466.
27. DeBoer M.D., Zhu X., Levasseur P.R., Inui A., Hu Z., Han G., Mitch W.E., Taylor J.E., Halem H.A., Dong J.Z., Datta R., Culler M.D., Marks D.L. Ghrelin treatment of chronic kidney disease: improvements in lean body mass and cytokine profile. Endocrinology 2008, 149:827-835.
28. DeBoer M.D., Zhu X.X., Levasseur P., Meguid M.M., Suzuki S., Inui A., Taylor J.E., Halem H.A., Dong J.Z., Datta R., Culler M.D., Marks D.L. Ghrelin treatment causes increased food intake and retention of lean body mass in a rat model of cancer cachexia. Endocrinology 2007, 148:3004-3012.
29. Deswal A., Petersen N.J., Feldman A.M., Young J.B., White B.G., Mann D.L. Cytokines and cytokine receptors in advanced heart failure: an analysis of the cytokine database from the Vesnarinone trial (VEST). Circulation 2001, 103:2055-2059.
30. Dixit V.D., Schaffer E.M., Pyle R.S., Collins G.D., Sakthivel S.K., Palaniappan R., Lillard J.W., Taub D.D. Ghrelin inhibits leptin- and activation-induced proinflammatory cytokine expression by human monocytes and T cells. J. Clin. Invest. 2004, 114:57-66.
31. Evans W.J., Morley J.E., Argiles J., Bales C., Baracos V., Guttridge D., Jatoi A., Kalantar-Zadeh K., Lochs H., Mantovani G., Marks D., Mitch W.E., Muscaritoli M., Najand A., Ponikowski P., Rossi Fanelli F., Schambelan M., Schols A., Schuster M., Thomas D., Wolfe R., Anker S.D. Cachexia: a new definition. Clin. Nutr. 2008, 27:793-799.
32. Falconer J.S., Fearon K.C., Ross J.A., Elton R., Wigmore S.J., Garden O.J., Carter D.C. Acute-phase protein response and survival duration of patients with pancreatic cancer. Cancer 1995, 75:2077-2082.
33. Fearon K.C. The Sir David Cuthbertson Medal Lecture 1991. The mechanisms and treatment of weight loss in cancer. Proc. Nutr. Soc. 1992, 51:251-265.
34. Garcia J., Boccia R., Graham C., Kumor K., Polvino W. A Phase II, randomized, placebo-controlled, double blind study of the efficacy and safety of RC-1291 for the treatment of cancer-cachexia. Abstract 2007. J. Clin. Oncol. 2007, 25(Suppl.).
35. Garcia J.M., Cata J.P., Dougherty P.M., Smith R.G. Ghrelin prevents cisplatin-induced mechanical hyperalgesia and cachexia. Endocrinology 2008, 149:455-460.
36. Garcia J.M., Garcia-Touza M., Hijazi R.A., Taffet G., Epner D., Mann D., Smith R.G., Cunningham G.R., Marcelli M. Active ghrelin levels and active to total ghrelin ratio in cancer-induced cachexia. J. Clin. Endocrinol. Metab. 2005, 90:2920-2926.
37. 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.
38. Granado M., Priego T., Martin A.I., Villanua M.A., Lopez-Calderon A. Anti-inflammatory effect of the ghrelin agonist growth hormone-releasing peptide-2 (GHRP-2) in arthritic rats. Am. J. Physiol. Endocrinol. Metab. 2005, 288:E486-492.
39. Gutierrez J.A., Solenberg P.J., Perkins D.R., Willency J.A., Knierman M.D., Jin Z., Witcher D.R., Luo S., Onyia J.E., Hale J.E. Ghrelin octanoylation mediated by an orphan lipid transferase. Proc. Natl. Acad. Sci. U.S.A. 2008, 105:6320-6325.
40. Hanada T., Toshinai K., Kajimura N., Nara-Ashizawa N., Tsukada T., Hayashi Y., Osuye K., Kangawa K., Matsukura S., Nakazato M. Anti-cachectic effect of ghrelin in nude mice bearing human melanoma cells. Biochem. Biophys. Res. Commun. 2003, 301:275-279.
41. Itoh T., Nagaya N., Yoshikawa M., Fukuoka A., Takenaka H., Shimizu Y., Haruta Y., Oya H., Yamagishi M., Hosoda H., Kangawa K., Kimura H. Elevated plasma ghrelin level in underweight patients with chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 2004, 170:879-882.
42. Kalantar-Zadeh K., Balakrishnan V.S. The kidney disease wasting: inflammation, oxidative stress, and diet-gene interaction. Hemodial. Int. 2006, 10:315-325.
43. Kirchner H., Gutierrez J.A., Solenberg P.J., Pfluger P.T., Czyzyk T.A., Willency J.A., Schurmann A., Joost H.G., Jandacek R.J., Hale J.E., Heiman M.L., Tschop M.H. GOAT links dietary lipids with the endocrine control of energy balance. Nat. Med. 2009, 15:741-745.
44. Kodama T., Ashitani J., Matsumoto N., Kangawa K., Nakazato M. Ghrelin treatment suppresses neutrophil-dominant inflammation in airways of patients with chronic respiratory infection. Pulm. Pharmacol. Ther. 2008, 21:774-779.
45. 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.
46. Laviano A., Inui A., Marks D.L., Meguid M.M., Pichard C., Rossi Fanelli F., Seelaender M. Neural control of the anorexia-cachexia syndrome. Am. J. Physiol. Endocrinol. Metab. 2008, 295:E1000-1008.
47. Lear P.V., Iglesias M.J., Feijoo-Bandin S., Rodriguez-Penas D., Mosquera-Leal A., Garcia-Rua V., Gualillo O., Ghe C., Arnoletti E., Muccioli G., Dieguez C., Gonzalez-Juanatey J.R., Lago F. Des-acyl ghrelin has specific binding sites and different metabolic effects from ghrelin in cardiomyocytes. Endocrinology 2010, 151:3286-3298.
48. Levine B., Kalman J., Mayer L., Fillit H.M., Packer M. Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. N. Engl. J. Med. 1990, 323:236-241.
49. Li L., Zhang L.K., Pang Y.Z., Pan C.S., Qi Y.F., Chen L., Wang X., Tang C.S., Zhang J. Cardioprotective effects of ghrelin and des-octanoyl ghrelin on myocardial injury induced by isoproterenol in rats. Acta Pharmacol. Sin. 2006, 27:527-535.
50. Liu Y.L., Malik N.M., Sanger G.J., Andrews P.L. Ghrelin alleviates cancer chemotherapy-associated dyspepsia in rodents. Cancer Chemother. Pharmacol. 2006, 58:326-333.
51. Locatelli F., Canaud B., Eckardt K.U., Stenvinkel P., Wanner C., Zoccali C. Oxidative stress in end-stage renal disease: an emerging threat to patient outcome. Nephrol. Dial. Transplant. 2003, 18:1272-1280.
52. Lundholm K., Gunnebo L., Korner U., Iresjo B.M., Engstrom C., Hyltander A., Smedh U., Bosaeus I. Effects by daily long term provision of ghrelin to unselected weight-losing cancer patients: a randomized double-blind study. Cancer 2010, 116:2044-2052.
53. Maki R.G. Small is beautiful: insulin-like growth factors and their role in growth, development, and cancer. J. Clin. Oncol. 2010, 28:4985-4995.
54. Malendowicz W., Ziolkowska A., Szyszka M., Kwias Z. Elevated blood active ghrelin and unaltered total ghrelin and obestatin concentrations in prostate carcinoma. Urol. Int. 2009, 83:471-475.
55. Marks D.L., Ling N., Cone R.D. Role of the central melanocortin system in cachexia. Cancer Res. 2001, 61:1432-1438.
56. Mitch W.E., Goldberg A.L. Mechanisms of muscle wasting. The role of the ubiquitin-proteosome pathway. N. Engl. J. Med. 1996, 335:1897-1905.
57. Muscaritoli M., Molfino A., Bollea M.R., Rossi Fanelli F. Malnutrition and wasting in renal disease. Curr. Opin. Clin. Nutr. Metab. Care 2009, 12:378-383.
58. Muscaritoli M., Molfino A., Chiappini M.G., Laviano A., Ammann T., Spinsanti P., Melchiorri D., Inui A., Alegiani F., Rossi Fanelli F. Anorexia in hemodialysis patients: the possible role of des-acyl ghrelin. Am. J. Nephrol. 2007, 27:360-365.
59. 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.
60. Nagaya N., Miyatake K., Uematsu M., Oya H., Shimizu W., Hosoda H., Kojima M., Nakanishi N., Mori H., Kangawa K. Hemodynamic, renal, and hormonal effects of ghrelin infusion in patients with chronic heart failure. J. Clin. Endocrinol. Metab. 2001, 86:5854-5859.
61. Nagaya N., Moriya J., Yasumura Y., Uematsu M., Ono F., Shimizu W., Ueno K., Kitakaze M., Miyatake K., Kangawa K. Effects of ghrelin administration on left ventricular function, exercise capacity, and muscle wasting in patients with chronic heart failure. Circulation 2004, 110:3674-3679.
62. Nagaya N., Uematsu M., Kojima M., Date Y., Nakazato M., Okumura H., Hosoda H., Shimizu W., Yamagishi M., Oya H., Koh H., Yutani C., Kangawa K. Elevated circulating level of ghrelin in cachexia associated with chronic heart failure: relationships between ghrelin and anabolic/catabolic factors. Circulation 2001, 104:2034-2038.
63. Nagaya N., Uematsu M., Kojima M., Ikeda Y., Yoshihara F., Shimizu W., Hosoda H., Hirota Y., Ishida H., Mori H., Kangawa K. Chronic administration of ghrelin improves left ventricular dysfunction and attenuates development of cardiac cachexia in rats with heart failure. Circulation 2001, 104:1430-1435.
64. 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.
65. Nass R., Pezzoli S.S., Oliveri M.C., Patrie J.T., Harrell F.E., Clasey J.L., Heymsfield S.B., Bach M.A., Vance M.L., Thorner M.O. Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial. Ann. Intern. Med. 2008, 149:601-611.
66. Naufel M.F., Bordon M., de Aquino T.M., Ribeiro E.B., de Abreu Carvalhaes J.T. Plasma levels of acylated and total ghrelin in pediatric patients with chronic kidney disease. Pediatr. Nephrol. 2010, 25:2477-2482.
67. Neary N.M., Small C.J., Wren A.M., Lee J.L., Druce M.R., Palmieri C., Frost G.S., Ghatei M.A., Coombes R.C., Bloom S.R. Ghrelin increases energy intake in cancer patients with impaired appetite: acute, randomized, placebo-controlled trial. J. Clin. Endocrinol. Metab. 2004, 89:2832-2836.
68. Nikolopoulos D., Theocharis S., Kouraklis G. Ghrelin: a potential therapeutic target for cancer. Regul. Pept. 2010, 163:7-17.
69. Nishi Y., Hiejima H., Hosoda H., Kaiya H., Mori K., Fukue Y., Yanase T., Nawata H., Kangawa K., Kojima M. Ingested medium-chain fatty acids are directly utilized for the acyl modification of ghrelin. Endocrinology 2005, 146:2255-2264.
70. Perez-Fontan M., Cordido F., Rodriguez-Carmona A., Garcia-Naveiro R., Isidro M.L., Villaverde P., Garcia-Buela J. Acute plasma ghrelin and leptin responses to oral feeding or intraperitoneal hypertonic glucose-based dialysate in patients with chronic renal failure. Kidney Int. 2005, 68:2877-2885.
71. Rauchhaus M., Doehner W., Francis D.P., Davos C., Kemp M., Liebenthal C., Niebauer J., Hooper J., Volk H.D., Coats A.J., Anker S.D. Plasma cytokine parameters and mortality in patients with chronic heart failure. Circulation 2000, 102:3060-3067.
72. Scarlett J.M., Bowe D.D., Zhu X., Batra A.K., Grant W.F., Marks D.L. Genetic and pharmacologic blockade of central melanocortin signaling attenuates cardiac cachexia in rodent models of heart failure. J. Endocrinol. 2010, 206:121-130.
73. Schwenke D.O., Tokudome T., Kishimoto I., Horio T., Shirai M., Cragg P.A., Kangawa K. Early ghrelin treatment after myocardial infarction prevents an increase in cardiac sympathetic tone and reduces mortality. Endocrinology 2008, 149:5172-5176.
74. Shah K.G., Wu R., Jacob A., Blau S.A., Ji Y., Dong W., Marini C.P., Ravikumar T.S., Coppa G.F., Wang P. Human ghrelin ameliorates organ injury and improves survival after radiation injury combined with severe sepsis. Mol. Med. 2009, 15:407-414.
75. Shiiya T., Nakazato M., Mizuta M., Date Y., Mondal M.S., Tanaka M., Nozoe S., Hosoda H., Kangawa K., Matsukura S. Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion. J. Clin. Endocrinol. Metab. 2002, 87:240-244.
76. Shimizu Y., Nagaya N., Isobe T., Imazu M., Okumura H., Hosoda H., Kojima M., Kangawa K., Kohno N. Increased plasma ghrelin level in lung cancer cachexia. Clin. Cancer Res. 2003, 9:774-778.
77. 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.
78. Strasser F., Lutz T.A., Maeder M.T., Thuerlimann B., Bueche D., Tschop M., Kaufmann K., Holst B., Brandle M., von Moos R., Demmer R., Cerny T. Safety, tolerability and pharmacokinetics of intravenous ghrelin for cancer-related anorexia/cachexia: a randomised, placebo-controlled, double-blind, double-crossover study. Br. J. Cancer 2008, 98:300-308.
79. Tack J., Depoortere I., Bisschops R., Verbeke K., Janssens J., Peeters T. Influence of ghrelin on gastric emptying and meal-related symptoms in idiopathic gastroparesis. Aliment. Pharmacol. Ther. 2005, 22:847-853.
80. Tisdale M.J. Biology of cachexia. J. Natl. Cancer Inst. 1997, 89:1763-1773.
81. Tisdale M.J. Cachexia in cancer patients. Nat. Rev. Cancer 2002, 2:862-871.
82. Tong J., Prigeon R.L., Davis H.W., Bidlingmaier M., Kahn S.E., Cummings D.E., Tschop M.H., D'Alessio D. Ghrelin suppresses glucose-stimulated insulin secretion and deteriorates glucose tolerance in healthy humans. Diabetes 2010, 59:2145-2151.
83. Torre-Amione G., Kapadia S., Benedict C., Oral H., Young J.B., Mann D.L. Proinflammatory cytokine levels in patients with depressed left ventricular ejection fraction: a report from the Studies of Left Ventricular Dysfunction (SOLVD). J. Am. Coll. Cardiol. 1996, 27:1201-1206.
84. Toshinai K., Mondal M.S., Shimbara T., Yamaguchi H., Date Y., Kangawa K., Nakazato M. Ghrelin stimulates growth hormone secretion and food intake in aged rats. Mech. Ageing Dev. 2007, 128:182-186.
85. Tschop M., Smiley D.L., Heiman M.L. Ghrelin induces adiposity in rodents. Nature 2000, 407:908-913.
86. Vigano A., Donaldson N., Higginson I.J., Bruera E., Mahmud S., Suarez-Almazor M. Quality of life and survival prediction in terminal cancer patients: a multicenter study. Cancer 2004, 101:1090-1098.
87. von Haehling S., Lainscak M., Springer J., Anker S.D. Cardiac cachexia: a systematic overview. Pharmacol. Ther. 2009, 121:227-252.
88. von Haehling S., Stepney R., Anker S.D. Advances in understanding and treating cardiac cachexia: highlights from the 5th Cachexia Conference. Int. J. Cardiol. 2010, 144:347-349.
89. Wang W., Andersson M., Iresjo B.M., Lonnroth C., Lundholm K. Effects of ghrelin on anorexia in tumor-bearing mice with eicosanoid-related cachexia. Int. J. Oncol. 2006, 28:1393-1400.
90. Wren A.M., Seal L.J., Cohen M.A., Brynes A.E., Frost G.S., Murphy K.G., Dhillo W.S., Ghatei M.A., Bloom S.R. Ghrelin enhances appetite and increases food intake in humans. J. Clin. Endocrinol. Metab. 2001, 86:5992. http://www.clinicaltrials.gov/ (accessed 18.11.10.).
91. Wynne K., Giannitsopoulou K., Small C.J., Patterson M., Frost G., Ghatei M.A., Brown E.A., Bloom S.R., Choi P. 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.
92. Xin X., Ren A.J., Zheng X., Qin Y.W., Zhao X.X., Yuan W.J., Guo Z.F. Disturbance of circulating ghrelin and obestatin in chronic heart failure patients especially in those with cachexia. Peptides 2009, 30:2281-2285.
93. Xu X.B., Pang J.J., Cao J.M., Ni C., Xu R.K., Peng X.Z., Yu X.X., Guo S., Chen M.C., Chen C. GH-releasing peptides improve cardiac dysfunction and cachexia and suppress stress-related hormones and cardiomyocyte apoptosis in rats with heart failure. Am. J. Physiol. Heart Circ. Physiol. 2005, 289:H1643-1651.
94. Yakabi K., Sadakane C., Noguchi M., Ohno S., Ro S., Chinen K., Aoyama T., Sakurada T., Takabayashi H., Hattori T. Reduced ghrelin secretion in the hypothalamus of rats due to cisplatin-induced anorexia. Endocrinology 2010, 151:3773-3782.
95. 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.
96. Yoshimoto A., Mori K., Sugawara A., Mukoyama M., Yahata K., Suganami T., Takaya K., Hosoda H., Kojima M., Kangawa K., Nakao K. Plasma ghrelin and desacyl ghrelin concentrations in renal failure. J. Am. Soc. Nephrol. 2002, 13:2748-2752.
97. Zabel R., Ash S., King N., Bauer J. The relationship between subjective appetite sensations, markers of inflammation and appetite in dialysis patients. J. Hum. Nutr. Diet. 2009, 22:343-350.
98. Zhang W., Chai B., Li J.Y., Wang H., Mulholland M.W. Effect of des-acyl ghrelin on adiposity and glucose metabolism. Endocrinology 2008, 149:4710-4716.
99. Zhao T.J., Liang G., Li R.L., Xie X., Sleeman M.W., Murphy A.J., Valenzuela D.M., Yancopoulos G.D., Goldstein J.L., Brown M.S. Ghrelin O-acyltransferase (GOAT) is essential for growth hormone-mediated survival of calorie-restricted mice. Proc. Natl. Acad. Sci. U.S.A. 2010, 107:7467-7472.