Ghrelin and the brain-gut axis as a pharmacological target for appetite control

Current Pharmaceutical Design

Volumn 18, Issue 6, 2012, Pages 768-775

  Seim, Inge ^a   El Salhy, Magdy ^b,c   Hausken, Trygve ^b   Gundersen, Doris ^d   Chopin, Lisa ^a  

^a QUEENSLAND UNIVERSITY OF TECHNOLOGY   (Australia)

^b UNIVERSITY OF BERGEN   (Norway)

^c Stord Helse Fonna Hospital   (Norway)

^d Helse Fonna ^*  (Norway)

Author keywords

Appetite; Ghrelin; GHSR; GOAT; Peptide hormone

Indexed keywords

ACYLTRANSFERASE; ANAMORELIN; ANTIOBESITY AGENT; APPETITE STIMULANT; BIM 28131; G PROTEIN COUPLED RECEPTOR; GHRELIN; GHRELIN RECEPTOR; GROWTH HORMONE SECRETAGOGUE RECEPTOR; HEXARELIN; HORMONE RECEPTOR BLOCKING AGENT; IBUTAMOREN; INSULIN; JMV 2810; JMV 2959; JMV 3002; L 756867; MONOCLONAL ANTIBODY; MONOCLONAL ANTIBODY 33A; NOX B11; PLASMID VECTOR; RIBOSE; RIMONABANT; SUBSTANCE P ANTAGONIST; TRIAZOLE DERIVATIVE; UNCLASSIFIED DRUG; VACCINE; YIL 781; YIL 870;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; ADIPOGENESIS; ANOREXIA; ANOREXIA NERVOSA; APPETITE; ARTICLE; BARIATRIC SURGERY; BLOOD BRAIN BARRIER; BODY MASS; BRAIN; CACHEXIA; CATABOLISM; CONGESTIVE HEART FAILURE; DRUG DELIVERY SYSTEM; DRUG POTENCY; DRUG TARGETING; ENDOPLASMIC RETICULUM; ENERGY BALANCE; ENERGY EXPENDITURE; ENERGY METABOLISM; FEEDING; FOOD INTAKE; GASTRIC BANDING; GLUCOSE HOMEOSTASIS; HOMEOSTASIS; HUMAN; IMMUNOTHERAPY; KIDNEY DISEASE; KNOCKOUT MOUSE; MENOPAUSAL SYNDROME; MORBID OBESITY; NEOPLASM; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; OLIGONUCLEOTIDE THERAPY; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; PROTEIN PROCESSING; REGULATORY MECHANISM; STOMACH BYPASS; WEIGHT GAIN;

APPETITE; APPETITE DEPRESSANTS; BRAIN; GASTROINTESTINAL TRACT; GHRELIN; HUMANS; OBESITY;

EID: 84856424470     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/138161212799277806     Document Type: Article

References (124)

1. Castonguay TW, Applegate EA, Upton DE, Stern JS. Hunger and appetite: old concepts/new distinctions. Nutr Rev 1983; 41: 101-110.
2. Atkinson TJ. Central and peripheral neuroendocrine peptides and signalling in appetite regulation: considerations for obesity pharmacotherapy. Obes Rev 2008; 9: 108-120.
3. Field BC, Wren AM, Cooke D, Bloom SR. Gut hormones as potential new targets for appetite regulation and the treatment of obesity. Drugs 2008; 68: 147-163.
4. Broberger C. Brain regulation of food intake and appetite: molecules and networks. J Int Med 2005; 258: 301-327.
5. Morley JE. Appetite regulation by gut peptides. Annu Rev Nutr 1990; 10: 383-395.
6. Huda MS, Wilding JP, Pinkney JH. Gut peptides and the regulation of appetite. Obes Rev 2006; 7: 163-182.
7. Tymitz K, Engel A, McDonough S, Hendy MP, Kerlakian G. Changes in ghrelin levels following bariatric surgery: review of the literature. Obes Surg 2011; 21: 125-130.
8. Carlson MJ, Cummings DE. Prospects for an anti-ghrelin vaccine to treat obesity. Mol Interv 2006; 6: 249-252.
9. 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.
10. Dickson SL, Egecioglu E, Landgren S, Skibicka KP, Engel JA, Jerlhag E. The role of the central ghrelin system in reward from food and chemical drugs. Mol Cell Endocrinol 2011; 340: 80-87.
11. Isgaard J, Granata R. Ghrelin in cardiovascular disease and atherogenesis. Mol Cell Endocrinol 2011; 340: 59-64.
12. Steiger A, Dresler M, Schussler P, Kluge M. Ghrelin in mental health, sleep, memory. Mol Cell Endocrinol 2011; 340: 88-96.
13. Tena-Sempere M. Ghrelin as a pleotrophic modulator of gonadal function and reproduction. Nat Clin Pract Endocrinol Metab 2008; 4: 666-674.
14. Date Y, Murakami N, Toshinai K, 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.
15. Nakazato M, Murakami N, Date Y, et al. A role for ghrelin in the central regulation of feeding. Nature 2001; 409: 194-198.
16. Wren A, Small C, Ward H, et al. The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion. Endocrinology 2000; 141: 4325-4328.
17. Wren AM, Seal LJ, Cohen MA, et al. Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab 2001; 86: 5992.
18. Ariyasu H, Takaya K, Tagami T, et al. Stomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelinlike immunoreactivity levels in humans. J Clin Endocrinol Metab 2001; 86: 4753-4758.
19. Tschop M, Wawarta R, Riepl RL, et al. Post-prandial decrease of circulating human ghrelin levels. J Endocrinol Invest 2001; 24: RC19-RC21.
20. Cummings DE, Purnell JQ, Frayo RS, Schmidova K, Wisse BE, Weigle DS. A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes 2001; 50: 1714-1719.
21. Cummings DE, Frayo RS, 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.
22. le Roux CW, Neary NM, Halsey TJ, et al. Ghrelin does not stimulate food intake in patients with surgical procedures involving vagotomy. J Clin Endocrinol Metab 2005; 90: 4521-4524.
23. Skibicka KP, Dickson SL., Ghrelin and food reward: The story of potential underlying substrates. Peptides 2011; 32: 2265-2273.
24. Tschop M, Smiley DL, Heiman ML. Ghrelin induces adiposity in rodents. Nature 2000; 407: 908-913.
25. Wortley KE, del Rincon JP, Murray JD, et al. Absence of ghrelin protects against early-onset obesity. J Clin Invest 2005; 115: 3573-3578.
26. 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.
27. Nagaya N, Uematsu M, Kojima M, et al. Elevated circulating level of ghrelin in cachexia associated with chronic heart failure: relationships between ghrelin and anabolic/catabolic factors. Circulation 2001; 104: 2034-308.
28. Shimizu Y, Nagaya N, Isobe T, et al. Increased plasma ghrelin level in lung cancer cachexia. Clin Cancer Res 2003; 9: 774-778.
29. Tschop M, Weyer C, Tataranni PA, Devanarayan V, Ravussin E, Heiman ML. Circulating ghrelin levels are decreased in human obesity. Diabetes 2001; 50: 707-709.
30. Shiiya T, Nakazato M, Mizuta 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.
31. Cummings DE, Weigle DS, Frayo RS, et al. Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med 2002; 346: 1623-1630.
32. Hansen TK, Dall R, Hosoda H, et al. Weight loss increases circulating levels of ghrelin in human obesity. Clin Endocrinol 2002; 56: 203-206.
33. Druce MR, Wren AM, Park AJ, et al. Ghrelin increases food intake in obese as well as lean subjects. Int J Obes 2005; 29: 1130-1136.
34. Zahorska-Markiewicz B, Mizia-Stec K, Olszanecka-Glinianowicz M, Janowska J. Effect of weight reduction on serum ghrelin and TNFalpha concentrations in obese women. Eur J Int Med 2004; 15: 172-175.
35. Perreault M, Istrate N, Wang L, Nichols AJ, Tozzo E, Stricker-Krongrad A. Resistance to the orexigenic effect of ghrelin in dietary-induced obesity in mice: reversal upon weight loss. Int J Obes Relat Metab Disord 2004; 28: 879-885.
36. Briggs DI, Enriori PJ, Lemus MB, Cowley MA, Andrews ZB. Diet-induced obesity causes ghrelin resistance in arcuate NPY/AgRP neurons. Endocrinology 2010; 151: 4745-4755.
37. Soares JB, Roncon-Albuquerque R, Jr., Leite-Moreira A. Ghrelin and ghrelin receptor inhibitors: agents in the treatment of obesity. Exp Opin Ther Targets 2008; 12: 1177-1189.
38. Tan TM, Vanderpump M, Khoo B, Patterson M, Ghatei MA, Goldstone AP. Somatostatin infusion lowers plasma ghrelin without reducing appetite in adults with Prader-Willi syndrome. J Clin Endocrinol Metab 2004; 89: 4162-4165.
39. Sze L, Purtell L, Jenkins A, et al. Effects of a single dose of exenatide on appetite, gut hormones, and glucose homeostasis in adults with Prader-Willi syndrome. J Clin Endocrinol Metab 2011; 96: E1314-E1319
40. Tanaka M, Nakahara T, Kojima S, et al. Effect of nutritional rehabilitation on circulating ghrelin and growth hormone levels in patients with anorexia nervosa. Reg Pept 2004; 122: 163-168.
41. Waseem T, Javaid Ur R, Ahmad F, Azam M, Qureshi MA. Role of ghrelin axis in colorectal cancer: a novel association. Peptides 2008; 29: 1369-1376.
42. Karapanagiotou EM, Polyzos A, Dilana KD, et al. Increased serum levels of ghrelin at diagnosis mediate body weight loss in nonsmall cell lung cancer (NSCLC) patients. Lung Cancer 2009; 66: 393-398.
43. Wolf I, Sadetzki S, Kanety H, et al. Adiponectin, ghrelin, and leptin in cancer cachexia in breast and colon cancer patients. Cancer 2006; 106: 966-973.
44. Kerem M, Ferahkose Z, Yilmaz UT, et al. Adipokines and ghrelin in gastric cancer cachexia. World J Gastroenterol 2008; 14: 3633-3641.
45. Garcia JM, Garcia-Touza M, Hijazi RA, et al. Active ghrelin levels and active to total ghrelin ratio in cancer-induced cachexia. J Clin Endocrinol Metab 2005; 90: 2920-2926.
46. Chuang JC, Perello M, Sakata I, et al. Ghrelin mediates stressinduced food-reward behavior in mice. J Clin Invest 2011; 121: 2684-2692.
47. Skibicka KP, Hansson C, Egecioglu E, Dickson SL. Role of ghrelin in food reward: impact of ghrelin on sucrose self-administration and mesolimbic dopamine and acetylcholine receptor gene expression. Addict Biol 2011; doi: 10.1111/j.1369-1600.2010.00294.x.
48. Landgren S, Simms JA, Hyytia P, Engel JA, Bartlett SE, Jerlhag E. Ghrelin receptor (GHS-R1A) antagonism suppresses both operant alcohol self-administration and high alcohol consumption in rats. Addict Biol 2011; doi: 10.1111/j.1369-1600.2010.00280.x.
49. Landgren S, Simms JA, Thelle DS, et al. The ghrelin signalling system is involved in the consumption of sweets. PLoS One 2011; 6: e18170.
50. Chen CY, Asakawa A, Fujimiya M, Lee SD, Inui A. Ghrelin gene products and the regulation of food intake and gut motility. Pharmacol Rev 2009; 61: 430-481.
51. Yu H, Kim K. Direct nose-to-brain transfer of a growth hormone releasing neuropeptide, hexarelin after intranasal administration to rabbits. Int J Pharm 2009; 378: 73-79.
52. Ghigo E, Arvat E, Gianotti L, et al. Short-term administration of intranasal or oral Hexarelin, a synthetic hexapeptide, does not desensitize the growth hormone responsiveness in human aging. Eur J Endocrinol 1996; 135: 407-412.
53. Ghigo E, Arvat E, Gianotti L, et al. Growth hormone-releasing activity of hexarelin, a new synthetic hexapeptide, after intravenous, subcutaneous, intranasal, and oral administration in man. J Clin Endocrinol Metab 1994; 78: 693-698.
54. Laron Z, Frenkel J, Deghenghi R, Anin S, Klinger B, Silbergeld A. Intranasal administration of the GHRP hexarelin accelerates growth in short children. Clin Endocrinol 1995; 43: 631-635.
55. Laron Z, Frenkel J, Gil-Ad I, et al. Growth hormone releasing activity by intranasal administration of a synthetic hexapeptide (hexarelin). Clin Endocrinol 1994; 41: 539-541.
56. Xie QF, Wu CX, Meng QY, Li N. Ghrelin and truncated ghrelin variant plasmid vectors administration into skeletal muscle augments long-term growth in rats. Domest Anim Endocrinol 2004; 27: 155-164.
57. Smith RG, Sun Y, Jiang H, Albarran-Zeckler R, Timchenko N. Ghrelin receptor (GHS-R1A) agonists show potential as interventive agents during aging. Ann N Y Acad Sci 2007; 1119: 147-164.
58. Liu YL, Malik NM, Sanger GJ, Andrews PL. Ghrelin alleviates cancer chemotherapy-associated dyspepsia in rodents. Cancer Chemother Pharmacol 2006: 1-8.
59. Yakabi K, Sadakane C, Noguchi M, et al. Reduced ghrelin secretion in the hypothalamus of rats due to cisplatin-induced anorexia. Endocrinology 2010; 151: 3773-3782.
60. Deboer MD. Ghrelin and cachexia: Will treatment with GHSR-1a agonists make a difference for patients suffering from chronic wasting syndromes? Mol Cell Endocrinol 2011; 340: 97-105.
61. Hillman JB, Tong J, Tschop M. Ghrelin biology and its role in weight-related disorders. Discov Med 2011; 11: 521-528.
62. Wang W, Andersson M, Iresjo BM, Lonnroth C, Lundholm K. Effects of ghrelin on anorexia in tumor-bearing mice with eicosanoid-related cachexia. Int J Oncol 2006; 28: 1393-1400.
63. Hanada T, Toshinai K, Kajimura N, et al. Anti-cachectic effect of ghrelin in nude mice bearing human melanoma cells. Biochem Biophys Res Commun 2003; 301: 275-279.
64. Hanada T, Toshinai K, Date Y, et al. Upregulation of ghrelin expression in cachectic nude mice bearing human melanoma cells. Metabolism 2004; 53: 84-88.
65. Neary NM, Small CJ, Wren 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.
66. Lundholm K, Gunnebo L, Korner U, et al. Effects by daily long term provision of ghrelin to unselected weight-losing cancer patients: a randomized double-blind study. Cancer 2010; 116: 2044-2052.
67. DeBoer MD, Zhu XX, Levasseur P, et al. Ghrelin treatment causes increased food intake and retention of lean body mass in a rat model of cancer cachexia. Endocrinology 2007; 148: 3004-3012.
68. Garcia J, Boccia RV, Graham C, Kumor K, Polvino W. A phase II randomized, placebo-controlled, double-blind study of the efficacy and safety of RC-1291 (RC) for the treatment of cancer cachexia. J Clin Oncol 2007; 25: 9133
69. Garcia JM, Polvino WJ. 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, placebocontrolled, multiple-dose study in healthy volunteers. Oncologist 2007; 12: 594-600.
70. Chopin L, Walpole C, Seim I, et al. Ghrelin and cancer. Mol Cell Endocrinol 2011; 340: 65-69.
71. Scerif M, Goldstone AP, Korbonits M. Ghrelin in obesity and endocrine diseases. Mol Cell Endocrinol 2011; 340: 15-25.
72. Field BC, Chaudhri OB, Bloom SR. Bowels control brain: gut hormones and obesity. Nature reviews. Endocrinology 2010; 6: 444-453.
73. Date Y, Kojima M, Hosada H, et al. Ghrelin, a novel growth hormone releasing acylated peptide is synthesised in a distinct endocrine cell type in gastrointestinal tracts of rats and humans. Endocrinology 2000; 141: 4255-4261.
74. Lin E, Gletsu N, Fugate K, et al. The effects of gastric surgery on systemic ghrelin levels in the morbidly obese. Arch Surg 2004; 139: 780-784.
75. Holdstock C, Engstrom BE, Ohrvall M, Lind L, Sundbom M, Karlsson FA. Ghrelin and adipose tissue regulatory peptides: effect of gastric bypass surgery in obese humans. J Clin Endocrinol Metab 2003; 88: 3177-3183.
76. Helmling S, Maasch C, Eulberg D, et al. Inhibition of ghrelin action in vitro and in vivo by an RNA-Spiegelmer. Proc Natl Acad Sci USA 2004; 101: 13174-13179.
77. Shearman LP, Wang SP, Helmling S, et al. Ghrelin Neutralization by a Ribonucleic Acid-SPM Ameliorates Obesity in Diet-Induced Obese Mice. Endocrinology 2006; 147: 1517-1526.
78. Asakawa A, Inui A, Kaga T, et al. Antagonism of ghrelin receptor reduces food intake and body weight gain in mice. Gut 2003; 52: 947-952.
79. Kobelt P, Helmling S, Stengel A, et al. Anti-ghrelin Spiegelmer NOX-B11 inhibits neurostimulatory and orexigenic effects of peripheral ghrelin in rats. Gut 2006; 55: 788-792.
80. Becskei C, Bilik KU, Klussmann S, Jarosch F, Lutz TA, 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.
81. Lu SC, Xu J, Chinookoswong N, et al. An acyl-ghrelin-specific neutralizing antibody inhibits the acute ghrelin-mediated orexigenic effects in mice. Mol Pharmacol 2009; 75: 901-907.
82. Zorrilla EP, Iwasaki S, Moss JA, et al. Vaccination against weight gain. Proc Natl Acad Sci USA 2006; 103: 13226-13231.
83. Shimbara T, Mondal MS, Kawagoe T, et al. Central administration of ghrelin preferentially enhances fat ingestion. Neurosci Lett 2004; 369: 75-79.
84. Vizcarra JA, Kirby JD, Kim SK, Galyean ML. Active immunization against ghrelin decreases weight gain and alters plasma concentrations of growth hormone in growing pigs. Domest Anim Endocrinol 2007; 33: 176-189.
85. Zigman JM, Elmquist JK. In search of an effective obesity treatment: a shot in the dark or a shot in the arm? Proc Natl Acad Sci USA 2006; 103: 12961-12962.
86. Overington JP, Al-Lazikani B, Hopkins AL. How many drug targets are there? Nat Rev Drug Discov 2006; 5: 993-6.
87. Howard A, Feighner S, Cully D, et al. A receptor in pituitary and hypothalamus that functions in growth hormone release. Science 1996; 12: 137-145.
88. Esler WP, Rudolph J, Claus TH, et al. Small-molecule ghrelin receptor antagonists improve glucose tolerance, suppress appetite, and promote weight loss. Endocrinology 2007; 148: 5175-5185.
89. Holst B, Cygankiewicz A, Jensen TH, Ankersen M, Schwartz TW. High constitutive signaling of the ghrelin receptor--identification of a potent inverse agonist. Mol Endocrinol 2003; 17: 2201-2210.
90. Salome N, Haage D, Perrissoud D, et al. Anorexigenic and electrophysiological actions of novel ghrelin receptor (GHS-R1A) antagonists in rats. Eur J Pharmacol 2009; 612: 167-173.
91. Xin Z, Serby MD, Zhao H, et al. Discovery and pharmacological evaluation of growth hormone secretagogue receptor antagonists. J Med Chem 2006; 49: 4459-4469.
92. Moulin A, Ryan J, Martinez J, Fehrentz JA. Recent developments in ghrelin receptor ligands. ChemMedChem 2007; 2: 1242-1259.
93. Salome N, Hansson C, Taube M, et al. On the central mechanism underlying ghrelin's chronic pro-obesity effects in rats: new insights from studies exploiting a potent ghrelin receptor antagonist. J Neuroendocrinol 2009; 21: 777-785.
94. Chan CB, Leung PK, Wise H, Cheng CH. Signal transduction mechanism of the seabream growth hormone secretagogue receptor. FEBS Lett 2004; 577: 147-153.
95. Schioth HB, Muceniece R, Wikberg JE. Characterization of the binding of MSH-B, HB-228, GHRP-6 and 153N-6 to the human melanocortin receptor subtypes. Neuropeptides 1997; 31: 565-571.
96. 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.
97. Kilpelainen M, Riikonen J, Vlasova MA, et al. In vivo delivery of a peptide, ghrelin antagonist, with mesoporous silicon microparticles. J Control Release 2009; 137: 166-170.
98. Clegg DJ, Brown LM, Zigman JM, et al. Estradiol-dependent decrease in the orexigenic potency of ghrelin in female rats. Diabetes 2007; 56: 1051-1058.
99. Maletinska L, Matyskova R, Maixnerova J, et al. The Peptidic GHS-R antagonist [D-Lys(3)]GHRP-6 markedly improves adiposity and related metabolic abnormalities in a mouse model of postmenopausal obesity. Mol Cell Endocrinol 2011; 343: 55-62.
100. Rudolph J, Esler WP, O'Connor S, et al. Quinazolinone derivatives as orally available ghrelin receptor antagonists for the treatment of diabetes and obesity. J Med Chem 2007; 50: 5202-5216.
101. Seim I, Collet C, Herington AC, Chopin LK. Revised genomic structure of the human ghrelin gene and identification of novel exons, alternative splice variants and natural antisense transcripts. BMC Genomics 2007; 8: 298.
102. Seim I, Carter SL, Herington AC, Chopin LK. Complex organisation and structure of the ghrelin antisense strand gene GHRLOS, a candidate non-coding RNA gene. BMC Mol Biol 2008; 9: 95.
103. Mano-Otagiri A, Iwasaki-Sekino A, Nemoto T, et al. Genetic suppression of ghrelin receptors activates brown adipocyte function and decreases fat storage in rats. Regul Pept 2010; 160: 81-90.
104. Yang J, Brown MS, Liang G, Grishin NV, Goldstein JL. Identification of the acyltransferase that octanoylates ghrelin, an appetite-stimulating peptide hormone. Cell 2008; 132: 387-396.
105. Gutierrez JA, Solenberg PJ, Perkins DR, et al. Ghrelin octanoylation mediated by an orphan lipid transferase. Proc Natl Acad Sci USA 2008; 105: 6320-6325.
106. Lim CT, Kola B, Grossman A, Korbonits M. The expression of ghrelin O-acyltransferase (GOAT) in human tissues. Endocr J 2011; 58: 707-710.
107. Sakata I, Yang J, Lee CE, et al. Colocalization of ghrelin Oacyltransferase and ghrelin in gastric mucosal cells. American journal of physiology. Endocrinol Metab 2009; 297: E134-F141.
108. Kirchner H, Gutierrez JA, Solenberg PJ, et al. GOAT links dietary lipids with the endocrine control of energy balance. Nat Med 2009; 15: 741-745.
109. Kojima M, Hosodo H, Date Y, Nakazato M, Matsuo H, Kanagawa K. Ghrelin is a growth hormone releasing acylated peptide from stomach. Nature 1999; 402: 656-660.
110. Garner AL, Janda KD. A small molecule antagonist of ghrelin Oacyltransferase (GOAT). Chem Commun 2011; 47: 7512-7514.
111. Barnett BP, Hwang Y, Taylor MS, et al. Glucose and weight control in mice with a designed ghrelin O-acyltransferase inhibitor. Science 2010; 330: 1689-1692.
112. Zhao TJ, Liang G, Li RL, et al. Ghrelin O-acyltransferase (GOAT) is essential for growth hormone-mediated survival of calorierestricted mice. Proc Natl Acad Sci USA 2010; 107: 7467-7472.
113. Yang J, Zhao TJ, Goldstein JL, Brown MS. Inhibition of ghrelin Oacyltransferase (GOAT) by octanoylated pentapeptides. Proc Natl Acad Sci USA 2008; 105: 10750-10755.
114. Mayorov AV, Amara N, Chang JY, et al. Catalytic antibody degradation of ghrelin increases whole-body metabolic rate and reduces refeeding in fasting mice. Proc Natl Acad Sci USA 2008; 105: 17487-17492.
115. Satou M, Nishi Y, Yoh J, Hattori Y, Sugimoto H. Identification and characterization of acyl-protein thioesterase 1/lysophospholipase I as a ghrelin deacylation/lysophospholipid hydrolyzing enzyme in fetal bovine serum and conditioned medium. Endocrinology 2010; 151: 4765-4775.
116. Eubanks LM, Stowe GN, De Lamo Marin S, Mayorov AV, Hixon MS, Janda KD. Identification of alpha(2) Macroglobulin as a Major Serum Ghrelin Esterase. Angew Chem 2011; 50: 10699-10702.
117. 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.
118. 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.
119. Castaneda TR, Tong J, Datta R, Culler M, Tschop MH. Ghrelin in the regulation of body weight and metabolism. Front Neuroendocrinol 2010; 31: 44-60.
120. Baatar D, Patel K, Taub DD. The effects of ghrelin on inflammation and the immune system. Mol Cell Endocrinol 2011; 340: 44-58.
121. Granata R, Isgaard J, Alloatti G, Ghigo E. Cardiovascular actions of the ghrelin gene-derived peptides and growth hormone-releasing hormone. Exp Biol Med (Maywood) 2011; 236: 505-514.
122. Ukkola O. Ghrelin in Type 2 diabetes mellitus and metabolic syndrome. Mol Cell Endocrinol 2011; 340: 26-8.
123. Asakawa A, Ataka K, Fujino K, et al. Ghrelin family of peptides and gut motility. J Gastroenterol Hepatol 2011; 26: 73-74.
124. Schellekens H, Dinan TG, Cryan JF. Lean mean fat reducing ghrelin machine: hypothalamic ghrelin and ghrelin receptors as therapeutic targets in obesity. Neuropharmacology 2010; 58: 2-16.