The role of ghrelin in weight-regulation disorders: Implications in clinical practice

Hormones

Volumn 13, Issue 4, 2014, Pages 458-475

  Solomou, Solomis ^a   Korbonits, Márta ^a  

^a QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

Author keywords

Anorexia; Ghrelin; GHSR; Obesity; Prader Willi syndrome

Indexed keywords

ANAMORELIN; ANTI GHRELIN VACCINE; ANTIOBESITY AGENT; GHRELIN; GHRELIN O ACYLTRANSFERASE INHIBITOR; GHRELIN RECEPTOR; GHRELIN RECEPTOR AGONIST; GHRELIN RECEPTOR ANTAGONIST; GHRELIN RECEPTOR INVERSE AGONIST; HORMONE RECEPTOR AFFECTING AGENT; NOX B 11; NOX B 11 2; NOX B 11 3; OCTREOTIDE; PLACEBO; PROTEIN GHSR1A; PROTEIN GHSR1B; UNCLASSIFIED DRUG; VACCINE; YIL 781;

ANOREXIA; ANOREXIA NERVOSA; APPETITE; BITTER TASTE; BULIMIA; CACHEXIA; CLINICAL PRACTICE; EATING; FEEDBACK SYSTEM; GLYCEMIC CONTROL; HORMONE STRUCTURE; HUMAN; NONHUMAN; OBESITY; PRADER WILLI SYNDROME; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; REWARD; SIGNAL TRANSDUCTION; TASTE BUD; VACCINATION; ANIMAL; BODY WEIGHT; CHEMISTRY; EATING DISORDER; ENERGY METABOLISM; GENETICS; METABOLISM; NUTRITIONAL DISORDER; PHYSIOLOGY; STRUCTURE ACTIVITY RELATION;

ANIMALS; BODY WEIGHT; CACHEXIA; EATING DISORDERS; ENERGY METABOLISM; GHRELIN; HUMANS; NUTRITION DISORDERS; OBESITY; PRADER-WILLI SYNDROME; SIGNAL TRANSDUCTION; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84916223754     PISSN: 11093099     EISSN: None     Source Type: Journal    
DOI: 10.14310/horm.2002.1551     Document Type: Review

References (139)

1. Leite-Moreira AF, Rocha-Sousa A, Henriques-Coelho T 2007 Cardiac, skeletal, and smooth muscle regulation by ghrelin. In: L Gerald (ed) Vitam Horm, Academic Press; pp, 207-238.
2. van der Velde M, Delhanty P, van der Eerden B, van der Lely AJ, van Leeuwen J 2007 Ghrelin and Bone. In: L Gerald (ed) Vitam Horm, Academic Press; pp, 239-258.
3. Fuglsang J 2007 Ghrelin in pregnancy and lactation. In: L Gerald (ed) Vitam Horm, Academic Press; pp, 259-284.
4. Tena-Sempere M 2007 Ghrelin and reproduction: ghrelin as novel regulator of the gonadotropic axis. In: L Gerald (ed) Vitam Horm, Academic Press; pp, 285-300.
5. Kemp BA, Howell NL, Gildea JJ, Keller SR, Padia SH, 2013 Intrarenal ghrelin receptors regulate ENaCdependent sodium reabsorption by a cAMP-dependent pathway. Kidney Int 84: 501-508.
6. Altınova AE, Törüner FB, Aktürk M, et al, 2006 Reduced serum acylated ghrelin levels in patients with hyperthyroidism. Horm Res 65: 295-299.
7. Ates Y, Degertekin B, Erdil A, Yaman H, Dagalp K, 2008 Serum ghrelin levels in inflammatory bowel disease with relation to disease activity and nutritional status. Dig Dis Sci 53: 2215-2221.
8. Freda PU, Reyes CM, Conwell IM, Sundeen RE, Wardlaw SL, 2003 Serum ghrelin levels in acromegaly: effects of surgical and long-acting octreotide therapy. J Clin Endocrinol Metabol 88: 2037-2044.
9. Kadoglou NPE, Lampropoulos S, Kapelouzou A, et al, 2010 Serum levels of apelin and ghrelin in patients with acute coronary syndromes and established coronary artery disease-KOZANI STUDY. Transl Res 155: 238-246.
10. Libè R, Morpurgo PS, Cappiello V, et al, 2005 Ghrelin and adiponectin in patients with Cushing's disease before and after successful transsphenoidal surgery. Clin Endocrinol (Oxf) 62: 30-36.
11. Monajemzadeh M, Mokhtari S, Motamed F, et al, 2013 Plasma ghrelin levels in children with cystic fibrosis and healthy children. Arch Med Sci 9: 93-97.
12. Nahata M, Muto S, Oridate N, et al, 2012 Impaired ghrelin signaling is associated with gastrointestinal dysmotility in rats with gastroesophageal reflux disease. Am J Physiol Gastrointest Liver Physiol 303: G42-G53.
13. Nweneka C, Prentice A, 2011 Helicobacter pylori infection and circulating ghrelin levels - A systematic review. BMC Gastroenterol 11: 7.
14. Pinsker JE, Ondrasik D, Chan D, et al, 2011 Total and acylated ghrelin levels in children with poor growth. Pediatr Res 69: 517-521.
15. Pöykkö SM, Kellokoski E, Hörkkö S, et al, 2003 Low plasma ghrelin is associated with insulin resistance, hypertension, and the prevalence of type 2 diabetes. Diabetes 52: 2546-2553.
16. Schöfl C, Horn R, Schill T, et al, 2002 Circulating ghrelin Levels in patients with polycystic ovary syndrome. J Clin Endocrinol Metab 87: 4607-4610.
17. Selimoglu MA, Altinkaynak S, Ertekin V, Akcay F, 2006 Serum ghrelin levels in children with celiac disease. J Clin Gastroenterol 40: 191-194.
18. Yilmaz H, Gerdan V, Kozaci D, et al, 2012 Ghrelin and adipokines as circulating markers of disease activity in patients with Takayasu arteritis. Arthritis Res Ther 14: R272.
19. Kojima M, Hosoda H, Date Y, et al, 1999 Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402: 656-660.
20. Yang J, Brown MS, Liang G, Grishin NV, Goldstein JL, 2008 Identification of the acyltransferase that octanoylates ghrelin, an appetite-stimulating peptide hormone. Cell 132: 387-396.
21. Hosoda H, Kojima M, Matsuo H, Kangawa K, 2000 Ghrelin and des-acyl ghrelin: Two major forms of rat ghrelin peptide in gastrointestinal tissue. Biochem Biophys Res Commun 279: 909-913.
22. Heppner KM, Piechowski CL, Müller A, et al, 2013 Both acyl and des-acyl ghrelin regulate adiposity and glucose metabolism via CNS ghrelin receptors. Diabetes 63: 122-131.
23. Leung P-K, Chow KBS, Lau P-N, et al, 2007 The truncated ghrelin receptor polypeptide (GHS-R1b) acts as a dominant-negative mutant of the ghrelin receptor. Cell Signal 19: 1011-1022.
24. Gnanapavan S, Kola B, Bustin S, et al, 2002 The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. J Clin Endocrinol Metab 87: 2988-2988.
25. Lango Allen H, Estrada K, Lettre G, et al, 2010 Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature 467: 832-838.
26. Ogiso K, Asakawa A, Amitani H, Inui A, 2011 Ghrelin and anorexia nervosa: A psychosomatic perspective. Nutrition 27: 988-993.
27. Amini P, Wadden D, Cahill F, et al, 2012 Serum acylated ghrelin is negatively correlated with the insulin resistance in the CODING study. PLoS ONE 7: e45657.
28. Tong J, Prigeon RL, Davis HW, et al, 2010 Ghrelin suppresses glucose-stimulated insulin secretion and deteriorates glucose tolerance in healthy humans. Diabetes 59: 2145-2151.
29. Tschop M, Smiley DL, Heiman ML, 2000 Ghrelin induces adiposity in rodents. Nature 407: 908-913.
30. Theander-Carrillo C, Wiedmer P, Cettour-Rose P, et al, 2006 Ghrelin action in the brain controls adipocyte metabolism. J Clin Invest 116: 1983-1993.
31. Cummings DE, Purnell JQ, Frayo RS, et al, 2001 A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes 50: 1714-1719.
32. Arafat AM, Weickert MO, Adamidou A, et al, 2013 The impact of insulin-independent, glucagon-induced suppression of total ghrelin on satiety in obesity and type 1 diabetes mellitus. J Clin Endocrinol Metab 98: 4133-4142.
33. Abizaid A, Liu Z-W, Andrews ZB, et al, 2006 Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite. J Clin Invest 116: 3229-3239.
34. Skibicka KP, Shirazi RH, Rabasa-Papio C, et al, 2013 Divergent circuitry underlying food reward and intake effects of ghrelin: Dopaminergic VTA -accumbens projection mediates ghrelin's effect on food reward but not food intake. Neuropharmacology 73: 274-283.
35. Perelló M, Zigman JM, 2012 The role of ghrelin in reward-based eating. Biol Psychiatry 72: 347-353.
36. Malik S, McGlone F, Bedrossian D, Dagher A, 2008 Ghrelin modulates brain activity in areas that control appetitive behavior. Cell Metab 7: 400-409.
37. Disse E, Bussier A-L, Veyrat-Durebex C, et al, 2010 Peripheral ghrelin enhances sweet taste food consumption and preference, regardless of its caloric content. Physiol Behav 101: 277-281.
38. Finger B, Dinan T, Cryan J, 2012 Diet-induced obesity blunts the behavioural effects of ghrelin: studies in a mouse-progressive ratio task. Psychopharmacology (Berl) 220: 173-181.
39. Perello M, Sakata I, Birnbaum S, et al, 2010 Ghrelin increases the rewarding value of high-fat diet in an orexin-dependent manner. Biol Psychiatry 67: 880-886.
40. Landgren S, Simms J, Thelle D, et al, 2011 The ghrelin signalling system is involved in the consumption of sweets. PLoS ONE 6: e18170.
41. Hillman JB, Tong J, Tschop M, 2011 Ghrelin biology and its role in weight-related disorders. Discov Med 11: 521.
42. Gil-Campos M, Aguilera CM, Ramirez-Tortosa MC, Cañete R, Gil A, 2010 Fasting and postprandial relationships among plasma leptin, ghrelin, and insulin in prepubertal obese children. Clin Nutr 29: 54-59.
43. Briggs DI, Enriori PJ, Lemus MB, Cowley MA, Andrews ZB, 2010 Diet-induced obesity causes ghrelin resistance in arcuate NPY/AgRP neurons. Endocrinology 151: 4745-4755.
44. Ukkola O, Ravussin E, Jacobson P, et al, 2001 Mutations in the preproghrelin/ghrelin gene associated with obesity in humans. J Clin Endocrinol Metab 86: 3996-3999.
45. Korbonits M, Gueorguiev M, O'Grady E, et al, 2002 A variation in the ghrelin gene increases weight and decreases insulin secretion in tall, obese children. J Clin Endocrinol Metab 87: 4005-4008.
46. Leskelä P, Ukkola O, Vartiainen J, et al, 2009 Fasting plasma total ghrelin concentrations in monozygotic twins discordant for obesity. Metabolism 58: 174-179.
47. Baessler A, Hasinoff MJ, Fischer M, et al, 2005 Genetic linkage and association of the growth hormone secretagogue receptor (ghrelin receptor) gene in human obesity. Diabetes 54: 259-267.
48. Garcia EA, Heude B, Petry CJ, et al, 2008 Ghrelin receptor gene polymorphisms and body size in children and adults. J Clin Endocrinol Metab 93: 4158-4161.
49. Pugliese-Pires PN, Fortin J-P, Arthur T, et al, 2011 Novel inactivating mutations in the GH secretagogue receptor gene in patients with constitutional delay of growth and puberty. Eur J Endocrinol 165: 233-241.
50. Ma X, Lin Y, Lin L, et al, 2012 Ablation of ghrelin receptor in leptin-deficient ob/ob mice has paradoxical effects on glucose homeostasis when compared with ablation of ghrelin in ob/ob mice. Am J Physiol Endocrinol Metab 303: E422-E431.
51. Saeed S, Bech P, Hafeez T, et al, 2013 Changes in levels of peripheral hormones controlling appetite are inconsistent with hyperphagia in leptin-deficient subjects. Endocrine 45: 401-408.
52. Cole SA, Butte NF, Voruganti VS, et al, 2010 Evidence that multiple genetic variants of MC4R play a functional role in the regulation of energy expenditure and appetite in Hispanic children. Am J Clin Nutr 91: 191-199.
53. Karra E, O'Daly OG, Choudhury AI, et al, 2013 A link between FTO, ghrelin, and impaired brain food-cue responsivity. J Clin Invest 123: 3539-3551.
54. Benedict C, Axelsson T, Söderberg S, et al, 2014 Brief communication: The fat mass and obesity-associated gene (FTO ) is linked to higher plasma levels of the hunger hormone ghrelin and lower serum levels of the satiety hormone leptin in older adults. Diabetes 63: 3955-3959.
55. Nicholls RD, Knepper JL, 2001 Genome organization, function, and imprinting in Prader-Willi and Angelman Syndromes. Annu Rev Genomics Hum Genet 2: 153- 175.
56. Bieth E, Eddiry S, Gaston V, et al, 2014 Highly restricted deletion of the SNORD116 region is implicated in Prader- Willi Syndrome. Eur J Hum Genet: doi: 10.1038/ejhg.
57. Cummings DE, Weigle DS, Frayo RS, et al, 2002 Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med 346: 1623-1630.
58. Haqq AM, Farooqi IS, O'Rahilly S, et al, 2003 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 88: 174-178.
59. DelParigi A, Tschöp M, Heiman ML, et al, 2002 High circulating ghrelin: a potential cause for hyperphagia and obesity in Prader-Willi Syndrome. J Clin Endocrinol Metab 87: 5461-5464.
60. Goldstone AP, Holland AJ, Butler JV, Whittington JE, 2012 Appetite hormones and the transition to hyperphagia in children with Prader-Willi syndrome. Int J Obes 36: 1564-1570.
61. Scerif M, Goldstone AP, Korbonits M, 2011 Ghrelin in obesity and endocrine diseases. Mol Cell Endocrinol 340: 15-25.
62. Choe YH, Song SY, Paik K-H, et al, 2005 Increased density of ghrelin-expressing cells in the gastric fundus and body in Prader-Willi Syndrome. J Clin Endocrinol Metab 90: 5441-5445.
63. Kojima M, Kangawa K, 2005 Ghrelin: Structure and Function. Physiol Rev 85: 495-522.
64. Goldstone AP, 2004 Prader-Willi syndrome: advances in genetics, pathophysiology and treatment. Trends Endocrinol Metab 15: 12-20.
65. Higgins S, Gueorguiev M, Korbonits M, 2007 Ghrelin, the peripheral hunger hormone. Ann Med 39: 116-136.
66. Feigerlová E, Diene G, Conte-Auriol F, et al, 2008 Hyperghrelinemia precedes obesity in Prader-Willi Syndrome. J Clin Endocrinol Metab 93: 2800-2805.
67. Bizzarri C, Rigamonti AE, Luce A, et al, 2010 Children with Prader-Willi syndrome exhibit more evident mealinduced responses in plasma ghrelin and peptide YY levels than obese and lean children. Eur J Endocrinol 162: 499-505.
68. Purtell L, Sze L, Loughnan G, et al, 2011 In adults with Prader-Willi syndrome, elevated ghrelin levels are more consistent with hyperphagia than high PYY and GLP-1 levels. Neuropeptides 45: 301-307.
69. Morris J, Twaddle S, 2007 Anorexia nervosa. BMJ 334: 894-898.
70. Hoek HW, 2006 Incidence, prevalence and mortality of anorexia nervosa and other eating disorders. Curr Opin Psychiatry 19: 389-394.
71. Monteleone P, Serritella C, Martiadis V, Scognamiglio P, Maj M, 2008 Plasma obestatin, ghrelin, and ghrelin/ obestatin ratio are increased in underweight patients with anorexia nervosa but not in symptomatic patients with bulimia nervosa. J Clin Endocrinol Metab 93: 4418-4421.
72. Nedvídková J, Krykorková I, Barták V, et al, 2003 Loss of meal-induced decrease in plasma ghrelin levels in patients with anorexia nervosa. J Clin Endocrinol Metab 88: 1678-1682.
73. Tolle V, Kadem M, Bluet-Pajot M-T, et al, 2003 Bal ance in ghrelin and leptin plasma levels in anorexia nervosa patients and constitutionally thin women. J Clin Endocrinol Metab 88: 109-116.
74. Miljic D, Pekic S, Djurovic M, et al, 2006 Ghrelin has partial or no effect on appetite, growth hormone, prolactin, and cortisol release in patients with anorexia nervosa. J Clin Endocrinol Metab 91: 1491-1495.
75. Asakawa A, Inui A, Fujimiya M, et al, 2005 Stomach regulates energy balance via acylated ghrelin and desacyl ghrelin. Gut 54: 18-24.
76. Koyama KI, Yasuhara D, Nakahara T, et al, 2010 Changes in acyl ghrelin, des-acyl ghrelin, and ratio of acyl ghrelin to total ghrelin with short-term refeeding in female inpatients with restricting-type anorexia nervosa. Horm Metab Res 42: 595-598.
77. Terashi M, Asakawa A, Harada T, et al, 2011 Ghrelin reactive autoantibodies in restrictive anorexia nervosa. Nutrition 27: 407-413.
78. Sedlackova D, Kopeckova J, Papezova H, et al, 2012 Comparison of a high-carbohydrate and high-protein breakfast effect on plasma ghrelin, obestatin, NPY and PYY levels in women with anorexia and bulimia nervosa. Nutr Metab 9: 52.
79. Germain N, Galusca B, Grouselle D, et al, 2010 Ghrelin and obestatin circadian levels differentiate bingeingpurging from restrictive anorexia nervosa. J Clin Endocrinol Metab 95: 3057-3062.
80. Dardennes RM, Zizzari P, Tolle V, et al, 2007 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 32: 106-113.
81. Müller TD, Tschöp MH, Jarick I, et al, 2011 Genetic variation of the ghrelin activator gene ghrelin O-acyltransferase (GOAT ) is associated with anorexia nervosa. J Psychiatr Res 45: 706-711.
82. Ando T, Komaki G, Nishimura H, et al, 2010 A ghrelin gene variant may predict crossover rate from restrictingtype anorexia nervosa to other phenotypes of eating disorders: a retrospective survival analysis. Psychiatr Genet 20: 153-159.
83. Kindler J, Bailer U, de Zwaan M, et al, 2011 No association of the neuropeptide Y (Leu7Pro) and ghrelin gene (Arg51Gln, Leu72Met, Gln90Leu) single nucleotide polymorphisms with eating disorders. Nord J Psychiatry 65: 203-207.
84. APA 2000 American Psychiatric Association. Diagnostic and statistical manual of mental disorders. Washington.
85. Tanaka M, Naruo T, Muranaga T, et al, 2002 Increased fasting plasma ghrelin levels in patients with bulimia nervosa. Eur J Endocrinol 146: R1-R3.
86. Kojima S, Nakahara T, Nagai N, et al, 2005 Altered ghrelin and peptide YY responses to meals in bulimia nervosa. Clin Endocrinol (Oxf) 62: 74-78.
87. Nakazato M, Hashimoto K, Shiina A, et al, 2004 No changes in serum ghrelin levels in female patients with bulimia nervosa. Prog Neuropsychopharmacol Biol Psychiatry 28: 1181-1184.
88. Atalayer D, Gibson C, Konopacka A, Geliebter A, 2013 Ghrelin and eating disorders. Prog Neuropsychopharmacol Biol Psychiatry 40: 70-82.
89. Cano S, Merkestein M, Skibicka K, Dickson S, Adan RH, 2012 Role of ghrelin in the pathophysiology of eating disorders. CNS Drugs 26: 281-296.
90. Troisi A, Di Lorenzo G, Lega I, et al, 2005 Plasma ghrelin in anorexia, bulimia, and binge-eating disorder: Relations with eating patterns and circulating concentrations of cortisol and thyroid hormones. Neuroendocrinology 81: 259-266.
91. Miyasaka K, Hosoya H, Sekime A, et al, 2006 Association of ghrelin receptor gene polymorphism with bulimia nervosa in a Japanese population. J Neural Transm 113: 1279-1285.
92. Evans WJ, Morley JE, Argilés J, et al, 2008 Cachexia: a new definition. Clin Nutr 27: 793-799.
93. Ashitani J, Matsumoto N, Nakazato M, 2009 Ghrelin and its therapeutic potential for cachectic patients. Peptides 30: 1951-1956.
94. Sharma R, Anker S, 2001 First cachexia symposium, Berlin, Germany, 1st-2nd December, 2000. Eur J Heart Fail 3: 751-754.
95. Itoh T, Nagaya N, Yoshikawa M, et al, 2004 Elevated plasma ghrelin level in underweight patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 170: 879-882.
96. Huang Q, Fan YZ, Ge BJ, Zhu Q, Tu ZY, 2007 Circulating ghrelin in patients with gastric or colorectal cancer. Dig Dis Sci 52: 803-809.
97. Wolf I, Sadetzki S, Kanety H, et al, 2006 Adiponectin, ghrelin, and leptin in cancer cachexia in breast and colon cancer patients. Cancer 106: 966-973.
98. Nikolopoulos D, Theocharis S, Kouraklis G, 2010 Ghrelin: A potential therapeutic target for cancer. Regul Pept 163: 7-17.
99. Aygen B, Dogukan A, Dursun F, et al, 2009 Ghrelin and obestatin levels in end-stage renal disease. J Int Med Res 37: 757-765.
100. Yoshimoto A, Mori K, Sugawara A, et al, 2002 Plasma ghrelin and desacyl ghrelin concentrations in renal failure. J Am Soc Nephrol 13: 2748-2752.
101. Garin MC, Burns CM, Kaul S, Cappola AR, 2013 The human experience with ghrelin administration. J Clin Endocrinol Metab 98: 1826-1837.
102. Broglio F, Gianotti L, Destefanis S, et al, 2004 The endocrine response to acute ghrelin administration is blunted in patients with anorexia nervosa, a ghrelin hypersecretory state. Clin Endocrinol (Oxf) 60: 592- 599.
103. Hotta M, Ohwada R, Akamizu T, et al, 2009 Ghrelin increases hunger and food intake in patients with restricting-type anorexia nervosa: A pilot study. Endocr J 56: 1119-1128.
104. Nagaya N, Moriya J, Yasumura Y, et al, 2004 Effects of ghrelin administration on left ventricular function, exercise capacity, and muscle wasting in patients with chronic heart failure. Circulation 110: 3674-3679.
105. Nagaya N, Itoh T, Murakami S, et al, 2005 Treatment of cachexia with ghrelin in patients with copd. Chest 128: 1187-1193.
106. Wynne K, Giannitsopoulou K, Small CJ, et al, 2005 Subcutaneous ghrelin enhances acute food intake in malnourished patients who receive maintenance peritoneal dialysis: A randomized, placebo-controlled trial. J Am Soc Nephrol 16: 2111-2118.
107. Neary NM, Small CJ, Wren AM, et al, 2004 Ghrelin increases energy intake in cancer patients with impaired appetite: acute, randomized, placebo-controlled trial. J Clin Endocrinol Metab 89: 2832-2836.
108. Akamizu T, Kangawa K, 2011 Therapeutic applications of ghrelin to cachexia utilizing its appetite-stimulating effect. Peptides 32: 2295-2300.
109. Porporato PE, Filigheddu N, Reano S, et al, 2013 Acylated and unacylated ghrelin impair skeletal muscle atrophy in mice. J Clin Invest 123: 611-622.
110. Özcan B, Neggers SJ, Miller AR, et al, 2013 Does des-acyl ghrelin improve glycemic control in obese diabetic subjects by decreasing acylated ghrelin levels? Eur J Endocrinol 170: 799-807.
111. Broglio F, Gottero C, Prodam F, et al, 2004 Non-acylated ghrelin counteracts the metabolic but not the neuroendocrine response to acylated ghrelin in humans. J Clin Endocrinol Metab 89: 3062-3065.
112. Benso A, St-Pierre DH, Prodam F, et al, 2012 Metabolic effects of overnight continuous infusion of unacylated ghrelin in humans. Eur J Endocrinol 166: 911-916.
113. Ejskjaer N, Wo JM, Esfandyari T, et al, 2013 A phase 2a, randomized, double-blind 28-day study of TZP-102 a ghrelin receptor agonist for diabetic gastroparesis. Neurogastroenterol Motil 25: e140-e150.
114. Depoortere I, 2009 Targeting the ghrelin receptor to regulate food intake. Regul Pept 156: 13-23.
115. Palus S, Schur R, Akashi YJ, et al, 2011 Ghrelin and its analogues, BIM-28131 and BIM-28125, improve body weight and regulate the expression of MuRF-1 and MAFbx in a rat heart failure model. PLoS ONE 6: e26865.
116. Lenk K, Palus S, Schur R, et al, 2013 Effect of ghrelin and its analogues, BIM-28131 and BIM-28125, on the expression of myostatin in a rat heart failure model. J Cachexia Sarcopenia Muscle 4: 63-69.
117. Garcia JM, Polvino WJ, 2007 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 12: 594-600.
118. Beck B, Richy S, Stricker-Krongrad A, 2004 Feeding response to ghrelin agonist and antagonist in lean and obese Zucker rats. Life Sci 76: 473-478.
119. Asakawa A, Inui A, Kaga T, et al, 2003 Antagonism of ghrelin receptor reduces food intake and body weight gain in mice. Gut 52: 947-952.
120. Esler WP, Rudolph J, Claus TH, et al, 2007 Smallmolecule ghrelin receptor antagonists improve glucose tolerance, suppress appetite, and promote weight loss. Endocrinology 148: 5175-5185.
121. Delporte C, 2012 Recent advances in potential clinical application of ghrelin in obesity. J Obes 2012: doi: 10.1155/2012/535624.
122. Holst B, Lang M, Brandt E, et al, 2006 Ghrelin receptor inverse agonists: identification of an active peptide core and its interaction epitopes on the receptor. Mol Pharmacol 70: 936-946.
123. Barnett BP, Hwang Y, Taylor MS, et al, 2010 Glucose and weight control in mice with a designed ghrelin O-acyltransferase inhibitor. Science 330: 1689-1692.
124. Yang TJ, Zhao TJ, Goldstein JL, Brown MS, 2008 Inhibition of ghrelin O-acyltransferase (GOAT ) by octanoylated pentapeptides. Proc Natl Acad Sci U S A 105: 10750-10755.
125. Janssen S, Laermans J, Verhulst PJ, et al, 2011 Bitter taste receptors and α-gustducin regulate the secretion of ghrelin with functional effects on food intake and gastric emptying. Proc Natl Acad Sci U S A 108: 2094- 2099.
126. Nørrelund H, Hansen TK, Ørskov H, et al, 2002 Ghrelin immunoreactivity in human plasma is suppressed by somatostatin. Clin Endocrinol (Oxf) 57: 539-546.
127. Haqq AM, Stadler DD, Rosenfeld RG, et al, 2003 Circulating ghrelin levels are suppressed by meals and octreotide therapy in children with Prader-Willi Syndrome. J Clin Endocrinol Metab 88: 3573-3576.
128. De Waele K, Ishkanian SL, Bogarin R, et al, 2008 Longacting octreotide treatment causes a sustained decrease in ghrelin concentrations but does not affect weight, behaviour and appetite in subjects with Prader-Willi syndrome. Eur J Endocrinol 159: 381-388.
129. Takeda H, Muto S, Nakagawa K, et al 2012 Chapter Twenty-One - Rikkunshito as a ghrelin enhancer. In: K Masayasu and K Kenji (eds) Methods in Enzymology, Academic Press; pp, 333-351.
130. Matsumura T, Arai M, Yonemitsu Y, et al, 2010 The traditional Japanese medicine Rikkunshito increases the plasma level of ghrelin in humans and mice. J Gastroenterol 45: 300-307.
131. Takeda H, Muto S, Hattori T, et al, 2010 Rikkunshito ameliorates the aging-associated decrease in ghrelin receptor reactivity via phosphodiesterase III inhibition. Endocrinology 151: 244-252.
132. Zorrilla EP, Iwasaki S, Moss JA, et al, 2006 Vaccination against weight gain. Proc Natl Acad Sci U S A 103: 13226-13231.
133. Andrade S, Carreira MC, Ribeiro A, et al, 2011 Development of an anti-ghrelin vaccine for obesity treatment. Endocr Rev 32: P2-305.
134. Lu SC, Xu J, Chinookoswong N, et al, 2009 An acylghrelin- specific neutralizing antibody inhibits the acute ghrelin-mediated orexigenic effects in mice. Mol Pharmacol 75: 901-907.
135. Cytos Biotechnology 2006. Phase I/IIa clinical trial with obese individuals shows no effect of CYT009- GhrQb on weight loss. http://www.cytos.com/uploads/ news/id180/Cytos Press E 061107.pdf Accessed 22nd September 2014.
136. Monteiro MP, 2011 Anti-ghrelin vaccine for obesity: a feasible alternative to dieting? Expert Rev Vaccines 10: 1363-1365.
137. Shearman LP, Wang SP, Helmling S, et al, 2006 Ghrelin neutralization by a Ribonucleic Acid-SPM ameliorates obesity in diet-induced obese mice. Endocrinology 147: 1517-1526.
138. Becskei C, Bilik KU, Klussmann S, et al, 2008 The anti-ghrelin spiegelmer NOX-B11-3 blocks ghrelinbut not fasting-induced neuronal activation in the hypothalamic arcuate nucleus. J Neuroendocrinol 20: 85-92.
139. Helmling S, Maasch C, Eulberg D, et al, 2004 Inhibition of ghrelin action in vitro and in vivo by an RNA-Spiegelmer. Proc Natl Acad Sci U S A 101: 13174-13179.