Energy homoeostasis: The roles of adipose tissue-derived hormones, peptide YY and Ghrelin

Obesity Facts

Volumn 2, Issue 2, 2009, Pages 117-125

  Hall, Jocelin ^a,c   Roberts, Rachel ^a   Vora, Niral ^b  

^a KING'S COLLEGE LONDON   (United Kingdom)

^b UNIVERSITY COLLEGE LONDON   (United Kingdom)

^c KING'S COLLEGE LONDON   (United Kingdom)

Author keywords

Adipose tissue; Appetite; Diabetes mellitus; Insulin resistance; Obesity

Indexed keywords

2,4 DIAMINOPYRIMIDINE DERIVATIVE; ADIPONECTIN; GHRELIN; GHRELIN RECEPTOR; HORMONE; INSULIN; LEPTIN; PEPTIDE YY; PEPTIDE YY [3-36]; RESISTIN;

ADIPOSE TISSUE; CLINICAL TRIAL; DRUG HALF LIFE; DRUG MECHANISM; ENERGY BALANCE; HOMEOSTASIS; HORMONAL REGULATION; HUMAN; INSULIN RESISTANCE; MORBID OBESITY; NAUSEA; NONHUMAN; OBESITY; PATHOGENESIS; PRIORITY JOURNAL; REGULATORY MECHANISM; REVIEW; STOMACH BYPASS; WEIGHT CONTROL; WEIGHT REDUCTION;

ADIPOKINES; ADIPOSE TISSUE; ENERGY METABOLISM; GHRELIN; HOMEOSTASIS; HUMANS; OBESITY; PEPTIDE YY;

EID: 67649220864     PISSN: 16624025     EISSN: 16624033     Source Type: Journal    
DOI: 10.1159/000208517     Document Type: Review

References (140)

1. WHO (ed): Obesity and Overweight: Fact sheet No 3111. WHO, 2006. www.who.int/mediacentre/ factsheets/fs311/en/index.html.
2. Kennedy GC: The role of depot fat in the hypothalamic control of food intake in the rat. Proc R Soc Lond B Biol Sci 1953;140:578-596.
3. Woods SC, Porte D Jr: The central nervous system, pancreatic hormones, feeding, and obesity. Adv Metab Disord 1978;9:283-312.
4. Coleman DL: Effects of parabiosis of obese with diabetes and normal mice. Diabetologia 1973;9:294- 298.
5. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM: Positional cloning of the mouse obese gene and its human homologue. Nature 1994;372:425-432.
6. Lee GH, Proenca R, Montez JM, Carroll KM, Darvishzadeh JG, Lee JI, Friedman JM: Abnormal splicing of the leptin receptor in diabetic mice. Nature 1996;379:632-635.
7. Farooqi IS, Jebb SA, Langmack G, Lawrence E, Cheetham CH, Prentice AM, Hughes IA, McCamish MA, O'Rahilly S: Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med 1999;341:879-884.
8. Farooqi IS, Matarese G, Lord GM, Keogh JM, Lawrence E, Agwu C, Sanna V, Jebb SA, Perna F, Fontana S, Lechler RI, DePaoli AM, O'Rahilly S: Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J Clin Invest 2002;110:1093-1103.
9. Ahima RS, Osei SY: Leptin signalling. Physiol Behav 2004;81:223-241.
10. Kloek C, Haq AK, Dunn SL, Lavery HJ, Banks AS, Myers MG Jr: Regulation of Jak kinases by intracellular leptin receptor sequences. J Biol Chem 2002;277:41547-41555.
11. Howard JK, Cave BJ, Oksanen LJ, Tzameli I, Bjørbaek C, Flier JS: Enhanced leptin sensitivity and attenuation of diet-induced obesity in mice with haploinsufficiency of Socs3. Nat Med 2004;10:734-738.
12. Mori H, Hanada R, Hanada T, Aki D, Mashima R, Nishinakamura H, Torisu T, Chien KR, Yasukawa H, Yoshimura A: Socs3 deficiency in the brain elevates leptin sensitivity and confers resistance to diet-induced obesity. Nat Med 2004;10:739-743.
13. Robertson SA, Leinninger GM, Myers MG Jr: Molecular and neural mediators of leptin action. Physiol Behav 2008;94:637-642.
14. Bjørbaek C, Kahn BB: Leptin signalling in the central nervous system and the periphery. Recent Prog Horm Res 2004;59:305-331. 15 Cohen P, Zhao C, Cai X, Montez JM, Rohani SC, Feinstein P, Mombaerts P, Friedman JM: Selective deletion of leptin receptor in neurons leads to obesity. J Clin Invest 2001;108:1113-1121.
15. Kowalski TJ, Liu SM, Leibel RL, Chua SC Jr: Transgenic complementation of leptin-receptor deficiency. I. Rescue of the obesity/diabetes phenotype of LEPR-null mice expressing a LEPR-B transgene. Diabetes 2001;50:425-435.
16. Morton GJ, Niswender KD, Rhodes CJ, Myers MG Jr, Blevins JE, Baskin DG, Schwartz MW: Arcuate nucleus-specific leptin receptor gene therapy attenuates the obesity phenotype of Koletsky (fa(k)/ fa(k)) rats. Endocrinology 2003;144:2016-2024.
17. Balthasar N, Coppari R, McMinn J, Liu SM, Lee CE, Tang V, Kenny CD, McGovern RA, Chua SC Jr, Elmquist JK, Lowell BB: Leptin receptor signalling in POMC neurons is required for normal body weight homeostasis. Neuron 2004;42:983-991.
18. Hommel JD, Trinko R, Sears RM, Georgescu D, Liu ZW, Gao XB, Thurmon JJ, Marinelli M, DiLeone RJ: Leptin receptor signalling in midbrain dopamine neurons regulates feeding. Neuron 2006;51:801-810.
19. Pelleymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D, Boone T, Collins F: Effects of the obese gene product on body weight regulation in ob/ob mice. Science 1995;269:540-543.
20. Shimizu H, Inoue K, Mori M: The leptin-dependent and -independent melanocortin signaling system: regulation of feeding and energy expenditure. J Endocrinol 2007;193:1-9.
21. Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D, Lallone RL, Burley SK, Friedman JM: Weight-reducing effects of the plasma protein encoded by the obese gene. Science 1995;269:543-546.
22. Maffei M, Halaas J, Ravussin E, Pratley RE, Lee GH, Zhang Y, Fei H, Kim S, Lallone R, Ranganathan S, Kern PA, Friedman JM: Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med 1995;1:1155-1161.
23. Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, Ohannesian JP, Marco CC, McKee LJ, Bauer TL: Serum immunoreactive- leptin concentrations in normal-weight and obese humans. N Engl J Med 1996;334:292-295.
24. Licinio J, Caglayan S, Ozata M, Yildiz BO, de Miranda PB, O'Kirwan F, Whitby R, Liang L, Cohen P, Bhasin S, Krauss RM, Veldhuis JD, Wagner AJ, DePaoli AM, McCann SM, Wong ML: Phenotypic effects of leptin replacement on morbid obesity, diabetes mellitus, hypogonadism, and behaviour in leptin-deficient adults. Proc Natl Acad Sci U S A 2004;101:4531-4536.
25. Westerterp-Plantenga MS, Saris WH, Hukshorn CJ, Campfield LA: Effects of weekly administration of pegylated recombinant human OB protein on appetite profile and energy metabolism in obese men. Am J Clin Nutr 2001;74:426-434.
26. Hukshorn CJ, Saris WH, Westerterp-Plantenga MS, Farid AR, Smith FJ, Campfield LA: Weekly subcutaneous pegylated recombinant native human leptin (PEG-OB) administration in obese men. J Clin Endocrinol Metab 2000;85:4003-4009.
27. Rosenbaum M, Sy M, Pavlovich K, Leibel RL, Hirsch J: Leptin reverses weight loss-induced changes in regional neural activity responses to visual food stimuli. J Clin Invest 2008;118:2583-2591.
28. Caro JF, Kolaczynski JW, Nyce MR, Ohannesian JP, Opentanova I, Goldman WH, Lynn RB, Zhang PL, Sinha MK, Considine RV: Decreased cerebrospinal-fluid/ serum leptin ratio in obesity: a possible mechanism for leptin resistance. Lancet 1996;348:159-61.
29. Levin BE, Dunn-Meynell AA, Banks WA: Obesity- prone rats have normal blood-brain barrier transport but defective central leptin signalling before obesity onset. Am J Physiol Regul Integr Comp Physiol 2004;286:R143-150.
30. Gabriely I, Ma XH, Yang XM, Rossetti L, Barzilai N: Leptin resistance during aging is independent of fat mass. Diabetes 2002;51:1016-1021.
31. Scherer PE, Williams S, Fogliano M, Baldini G, Lodish HF: A novel serum protein similar to C1q, produced exclusively in adipocytes. J Biol Chem 1995;270:26746-26749.
32. Pajvani UB, Du X, Combs TP, Berg AH, Rajala MW, Schulthess T, Engel J, Brownlee M, Scherer PE: Structure-function studies of the adipocyte-secreted hormone Acrp30/adiponectin: implications for metabolic regulation and bioactivity. J Biol Chem 2003;278:9073-9085.
33. Tsao TS, Tomas E, Murrey HE, Hug C, Lee DH, Ruderman NB, Heuser JE, Lodish HF: Role of disulfide bonds in Acrp30/adiponectin structure and signalling specificity: different oligomers activate different signal transduction pathways. J Biol Chem 2003;278:50810-50817.
34. Waki H, Yamauchi T, Kamon J, Ito Y, Uchida S, Kita S, Hara K, Hada Y, Vasseur F, Froguel P, Kimura S, Nagai R, Kadowaki T: Impaired multimerization of human adiponectin mutants associated with diabetes: molecular structure and multimer formation of adiponectin. J Biol Chem 2003;278:40352-40363.
35. Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S: Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 2003;423:762-769.
36. Maeda N, Funahashi T: Adiponectin knockout mice. Nippon Rinsho 2004;62:1067-1076.
37. Kubota N, Yano W, Kubota T, Yamauchi T, Itoh S, Kumagai H, Kozono H, Takamoto I, Okamoto S, Shiuchi T, Suzuki R, Satoh H, Tsuchida A, Moroi M, Sugi K, Noda T, Ebinuma H, Ueta Y, Kondo T, Araki E, Ezaki O, Nagai R, Tobe K, Terauchi Y, Ueki K, Minokoshi Y, Kadowak T: Adiponectin stimulates AMP-activated protein kinase in the hypothalamus and increases food intake. Cell Metab 2007;6:55-68.
38. Hu E, Liang P, Spiegelman BM: AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Biol Chem 1996;271;10697-10703.
39. Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, Mori Y, Ide T, Murakami K, Tsuboyama-Kasaoka N, Ezaki O, Akanuma Y, Gavrilova O, Vinson C, Reitman ML, Kagechika H, Shudo K, Yoda M, Nakano Y, Tobe K, Nagai R, Kimura S, Tomita M, Froguel P, Kadowaki T: The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 2001;7:941-946.
40. Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y, Nakayama O, Makishima M, Matsuda M, Shimomura I: Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest 2004;114:1752-1761.
41. Bruun JM, Lihn AS, Verdich C, Pedersen SB, Toubro S, Astrup A, Richelsen B: Regulation of adiponectin by adipose tissue-derived cytokines: in vivo and in vitro investigations in humans. Am J Physiol Endocrinol Metab 2003;285:E527-533.
42. Berg AH, Combs TP, Du X, Brownlee M, Scherer PE: The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nat Med 2001;7:947-953.
43. Mori Y, Otabe S, Dina C, Yasuda K, Populaire C, Lecoeur C, Vatin V, Durand E, Hara K, Okada T, Tobe K, Boutin P, Kadowaki T, Froguel P: Genome- wide search for type 2 diabetes in Japanese affected sib-pairs confirms susceptibility genes on 3q, 15q, and 20q and identifies two new candidate loci on 7p and 11p. Diabetes 2002;51:1247-1255.
44. Hara K, Boutin P, Mori Y, Tobe K, Dina C, Yasuda K, Yamauchi T, Otabe S, Okada T, Eto K, Kadowaki H, Hagura R, Akanuma Y, Yazaki Y, Nagai R, Tanitama M, Matsubara K, Yoda M, Nakano Y, Kimura S, Tomita M, Ito C, Froguel P, Kadowaki T: Genetic variation in the gene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population. Diabetes 2002;51:536-540.
45. Lindsay RS, Funahashi T, Hanso RL, Matsuzawa Y, Tanaka S, Tataranni PA: Adiponectin and development of type 2 diabetes in the Pima Indian population. Lancet 2002;360:57-58.
46. Wang C, Mao X, Wang L, Liu M, Wetzel M, Guan KL, Dong LQ, Liu F: Adiponectin sensitizes insulin signalling by reducing p70 S6 kinase-mediated serine phosphorylation of IRS-1. J Biol Chem 2007;282:7991-7996.
47. Okamoto M, Ohara-Imaizumi M, Kubota N, Hashimoto S, Eto K, Kanno T, Kubota T, Wakui M, Nagai R, Noda M, Nagamatsu S, Kadowaki T: Adiponectin induces insulin secretion in vivo and in vitro at low glucose concentration. Diabetologia 2008;51:827-835
48. Kubota N, Terauchi Y, Yamauchi T, Kubota T, Moroi M, Matsui J, Eto K, Yamashita T, Kamon J, Satoh H, Yano W, Froguel P, Nagai R, Kimura S, Kadowaki T, Noda T: Disruption of adiponectin causes insulin resistance and neointimal formation. J Biol Chem 2002;277:25863-25866.
49. Okamoto Y, Arita Y, Nishida M, Muraguchi M, Ouchi N, Takahashi M, Igura T, Inui Y, Kihara S, Nakamura T, Yamashita S, Miyagawa J, Funahashi T, Matsuzawa Y: An adipocyte-derived plasma protein, adiponectin, adheres to injured vascular walls. Horm Metab Res 2000;32:47-50.
50. Ouchi N, Kihara S, Arita Y, Maeda K, Kuriyama H, Okamoto Y, Hotta K, Nishida M, Takahashi M, Nakamura T, Yamashita S, Funahashi T, Matsuzawa Y: Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation 1999;100:2473-2476.
51. Arita Y, Kihara S, Ouchi N, Maeda K, Kuriyama H, Okamoto Y, Kumada M, Hotta K, Nishida M, Takahashi M, Nakamura T, Shimomura I, Muraguchi M, Ohmoto Y, Funahashi T, Matsuzawa Y: Adipocyte-derived plasma protein adiponectin acts as a platelet-derived growth factor-BB-binding protein and regulates growth factor-induced common postreceptor signal in vascular smooth muscle cell. Circulation 2002;105:2893-2898.
52. Ouchi N, Kihara S, Arita Y, Nishida M, Matsuyama A, Okamoto Y, Ishigami M, Kuriyama H, Kishida K, Nishizawa H, Hotta K, Muraguchi M, Ohmoto Y, Yamashita S, Funahashi T, Matsuzawa Y: Adipocyte- derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages. Circulation 2001;103:1057-1063.
53. Pischon T, Girman CJ, Hotamisligil GS, Rifai N, Hu FB, Rimm EB: Plasma adiponectin levels and risk of myocardial infarction in men. JAMA 2004;291:1730-1737.
54. Schnabel R, Messow CM, Lubos E, Espinola-Klein C, Rupprecht HJ, Bickel C, Sinning C, Tzikas S, Keller T, Genth-Zotz S, Lackner KJ, Münzel TF, Blankenberg S: Association of adiponectin with adverse outcome in coronary artery disease patients: results from the AtheroGene study. Eur Heart J 2008;29:649-657.
55. Lara-Castro C, Luo N, Wallace P, Klein RL, Garvey WT: Adiponectin multimeric complexes and the metabolic syndrome trait cluster. Diabetes 2006;55:249-259.
56. Von Eynatten M, Humpert PM, Bluemm A, Lepper PM, Hamann A, Allolio B, Naworth PP, Bierhaus A, Dugi KA: High-molecular weight adiponectin is independently associated with the extent of coronary artery disease in men. Atherosclerosis 2008;199:123-128.
57. Waki H, Yamauchi T, Kamon J, Ito Y, Uchida S, Kita S, Hara K, Hada Y, Vasseur F, Froguel P, Kimura S, Nagai R, Kadowaki T: Impaired multimerization of human adiponectin mutants associated with diabetes. Molecular structure and multimer formation of adiponectin. J Biol Chem 2003;278:40352-40363.
58. Schwartz S, Raskin P, Fonseca V, Graveline JF: Effect of troglitazone in insulin-treated patients with type II diabetes. N Engl J Med 1998;338:861-866.
59. Yilmaz MI, Sonmez A, Caglar K, Celik T, Yenicesu M, Eyjileten T, Acikel C, Oguz Y, Yavuz I, Vural A: Effect of antihypertensive agents on plasma adiponectin levels in hypertensive patients with metabolic syndrome. Nephrology (Carlton) 2007;12:147-153.
60. Nakamura T, Kodama Y, Takano H, Umetani K, Fujioka D, Saito Y: Increase in circulating levels of adiponectin after treatment with statin and fibrate in patients with coronary artery disease and hyperlipidemia. Atherosclerosis 2007;193:449-451.
61. Westphal S, Luley C: Preferential increase in highmolecular weight adiponectin after niacin. Atherosclerosis 2008;198:179-183.
62. Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA: The hormone resistin links obesity to diabetes. Nature 2001;409:307-312.
63. Holcomb IN, Kabakoff RC, Chan B, Baker TW, Gurney A, Henzel W, Nelson C, Lowman HB, Wright BD, Skelton NJ, Frantz GD, Tumas DB, Peale FV Jr, Shelton DL, Hebert CC: FIZZ1, a novel cysteine-rich secreted protein associated with pulmonary inflammation, defines a new gene family. EMBO J 2000;19:4046-4055.
64. Aruna B, Ghosh S, Singh AK, Mande SC, Srinivas V, Chauhan R, Ehtesham NZ: Human recombinant resistin protein displays a tendency to aggregate by forming intermolecular disulfide linkages. Biochemistry 2003;42:10554-10559.
65. Azuma K, Katsukawa F, Oguchi S, Murata M, Yamazaki H, Shimada A, Saruta T: Correlation between serum resistin level and adiposity in obese individuals. Obes Res 2003;11:997-1001.
66. Silha JV, Krsek M, Skrha JV, Sucharda P, Nyomba BL, Murphy LJ: Plasma resistin, adiponectin and leptin levels in lean and obese subjects: correlations with insulin resistance. Eur J Endocrinol 2003;149: 331-335.
67. Way JM, Görgün CZ, Tong Q, Uysal KT, Brown KK, Harrington WW, Oliver WR Jr, Willson TM, Kliewer SA, Hotamisligil GS: Adipose tissue resistin expression is severely suppressed in obesity and stimulated by peroxisome proliferatoractivated receptor gamma agonists. J Biol Chem 2001;276:25651-25653.
68. Heilbronn LK, Rood J, Janderova L, Albu JB, Kelley DE, Ravussin E, Smith SR: Relationship between serum resistin concentrations and insulin resistance in nonobese, obese, and obese diabetic subjects. J Clin Endocrinol Metab 2004;89:1844- 1848.
69. Beckers S, Peeters AV, de Freitas F, Mertens IL, Hendrickx JJ, Van Gaal LF, Van Hul W: Analysis of genetic variations in the resistin gene shows no associations with obesity in women. Obesity 2008;16:905-907.
70. Savage DB, Sewter CP, Klenk ES, Segal DG, Vidal-Puig A, Considine RV, O'Rahilly S: Resistin/ Fizz3 expression in relation to obesity and peroxisome proliferator-activated receptor-gamma action in humans. Diabetes 2001;50:2199-2202.
71. Michel MC, Beck-Sickinger A, Cox H, Doods HN, Herzog H, Larhammar D, Quirion R, Schwartz T, Westfall T: International Union of Pharmacology recommendations for the nomenclature of neuropeptide Y, peptide YY, and pancreatic polypeptide receptors. Pharmacol Rev 1998;50:143-150.
72. Adrian TE, Ferri GL, Bacarese-Hamilton AJ, Fuessl HS, Polak JM, Bloom SR: Human distribution and release of a putative new gut hormone, peptide YY. Gastroenterology 1985;89:1070-1077.
73. Ekblad E, Sundler F: Distribution of pancreatic polypeptide and peptide YY. Peptides 2002;23:251- 261.
74. Lin HC, Chey WY: Cholecystokinin and peptide YY are released by fat in either proximal or distal small intestine in dogs. Regul Pept 2003;114:131-135.
75. Oesch S, Rüegg C, Fischer B, Degen L, Beglinger C: Effect of gastric distension prior to eating on food intake and feelings of satiety in humans. Physiol Behav 2006;87:903-910.
76. Onaga T, Zabielski R, Kato S: Multiple regulation of peptide YY secretion in the digestive tract. Peptides 2002;23:279-290.
77. Batterham RL, Cowley MA, Small CJ, Herzog H, Cohen MA, Dakin CL, Wren AM, Brynes AE, Low MJ, Ghatei MA, Cone RD, Bloom SR: Gut hormone PYY(3-36) physiologically inhibits food intake. Nature 2002;418:650-654.
78. Grandt D, Schimiczek M, Beglinger C, Layer P, Goebell H, Eysselein VE, Reeve JR Jr: Two molecular forms of peptide YY (PYY) are abundant in human blood: characterization of a radioimmunoassay recognizing PYY 1-36 and PYY 3-36. Regul Pept 1994;51:151-159.
79. Lin HC, Zhao XT, Wang L, Wong H: Fat-induced ileal brake in the dog depends on peptide YY. Gastroenterology 1996;110:1491-1495.
80. Allen JM, Fitzpatrick ML, Yeats JC, Darcy K, Adrian TE, Bloom SR: Effects of peptide YY and neuropeptide Y on gastric emptying in man. Digestion 1984;30:255-262.
81. Hoentjen F, Hopman WP, Jansen JB: Effect of circulating peptide YY on gallbladder emptying in humans. Scand J Gastroenterol 2001;36:1086-1091.
82. Abbott CR, Monteiro M, Small CJ, Sajedi A, Smith KL, Parkinson JR, Ghatei MA, Bloom SR: The inhibitory effects of peripheral administration of peptide YY(3-36) and glucagon-like peptide-1 on food intake are attenuated by ablation of the vagal-brainstem-hypothalamic pathway. Brain Res 2005;1044:127-131.
83. Schwartz MW, Woods SC, Porte D Jr, Seeley RJ, Baskin DG: Central nervous system control of food intake. Nature 2000;404:661-671.
84. Nonaka N, Shioda S, Niehoff ML, Banks WA: Characterization of blood-brain barrier permeability to PYY3-36 in the mouse. J Pharmacol Exp Ther 2003;306:948-953.
85. Keire DA, Mannon P, Kobayashi M, Walsh JH, Solomon TE, Reeve JR Jr: Primary structures of PYY, [Pro(34)]PYY, and PYY-(3-36) confer different conformations and receptor selectivity. Am J Physiol Gastrointest Liver Physiol 2000;279: G126-131.
86. Acuna-Goycolea C, van den Pol AN: Peptide YY (3-36) inhibits both anorexigenic proopiomelanocortin and orexigenic neuropeptide Y neurons: implications for hypothalamic regulation of energy homeostasis. J Neurosci 2005;25:10510-10519.
87. Batterham RL, Cohen MA, Ellis SM, Le Roux CW, Withers DJ, Frost GS, Ghatei MA, Bloom SR: Inhibition of food intake in obese subjects by peptide YY3-36. N Engl J Med 2003;349:941-948.
88. Riediger T, Bothe C, Becskei C, Lutz TA: Peptide YY directly inhibits ghrelin-activated neurons of the arcuate nucleus and reverses fasting-induced c-Fos expression. Neuroendocrinology 2004;79: 317-326.
89. Sloth B, Davidsen L, Holst JJ, Flint A, Astrup A: Effect of subcutaneous injections of PYY1-36 and PYY3-36 on appetite, ad libitum energy intake, and plasma free fatty acid concentration in obese males. Am J Physiol Endocrinol Metab 2007;293: E604-609.
90. Le Roux CW, Batterham RL, Aylwin SJ, Patterson M, Borg CM, Wynne KJ, Kent A, Vincent RP, Gardiner J, Ghatei MA, Bloom SR: Attenuated peptide YY release in obese subjects is associated with reduced satiety. Endocrinology 2006;147:3-8.
91. Ma L, Tataranni PA, Hanson RL, Infante AM, Kobes S, Bogardus C, Baier LJ: Variations in peptide YY and Y2 receptor genes are associated with severe obesity in Pima Indian men. Diabetes 2005;54:1598-1602.
92. Lavebratt C, Alpman A, Persson B, Arner P, Hoffstedt J: Common neuropeptide Y2 receptor gene variant is protective against obesity among Swedish men. Int J Obes (Lond) 2006;30:453-459.
93. Viardot A, Heilbronn LK, Herzog H, Gregersen S, Campbell LV: Abnormal postprandial PYY response in insulin sensitive nondiabetic subjects with a strong family history of type 2 diabetes. Int J Obes (Lond) 2008;32:943-948.
94. Zwirska-Korczala K, Konturek SJ, Sodowski M, Wylezol M, Kuka D, Sowa P, Adamczyk-Sowa M, Kukla M, Berdowska A, Rehfeld JF, Bielanski W, Brzozowski T: Basal and postprandial plasma levels of PYY, ghrelin, cholecystokinin, gastrin and insulin in women with moderate and morbid obesity and metabolic syndrome. J Physiol Pharmacol 2007;58(suppl 1):13-35.
95. Misra M, Miller K, Tsai P, Gallagher K, Lin A, Lee N, Herzog D, Klibanski A: Elevated peptide YY levels in adolescent girls with anorexia nervosa. J Clin Endocrinol Metab 2006;91:1027-1033.
96. El-Salhy M, Suhr O, Danielsson A: Peptide YY in gastrointestinal disorders. Peptides 2002;23:397- 402.
97. Le Roux CW, Ghatei MA, Gibbs JS, Bloom SR: The putative satiety hormone PYY is raised in cardiac cachexia associated with primary pulmonary hypertension. Heart 2005;91:241-242.
98. Korner J, Bessler M, Cirilo LJ, Conwell IM, Daud A, Restuccia NL, Wardlaw SL: Effects of Rouxen- Y gastric bypass surgery on fasting and postprandial concentrations of plasma ghrelin, peptide YY, and insulin. J Clin Endocrinol Metab 2005;90:359-365.
99. Van den Hoek AM, Heijboer AC, Corssmit EP, Voshol PJ, Romijn JA, Havekes LM, Pijl H: PYY3-36 reinforces insulin action on glucose disposal in mice fed a high-fat diet. Diabetes 2004;53:1949-1952.
100. Boey D, Lin S, Karl T, Baldock P, Lee N, Enriquez R, Couzens M, Slack K, Dallmann R, Sainsbury A, Herzog H: Peptide YY ablation in mice leads to the development of hyperinsulinaemia and obesity. Diabetologia 2006;49:1360-1370.
101. Sloth B, Holst JJ, Flint A, Gregersen NT, Astrup A: Effects of PYY1-36 and PYY3-36 on appetite, energy intake, energy expenditure, glucose and fat metabolism in obese and lean subjects. Am J Physiol Endocrinol Metab 2007;292:E1062-1068.
102. Stock S, Leichner P, Wong AC, Ghatei MA, Kieffer TJ, Bloom SR, Chanoine JP: Ghrelin, peptide YY, glucose-dependent insulinotropic polypeptide, and hunger responses to a mixed meal in anorexic, obese, and control female adolescents. J Clin Endocrinol Metab 2007;90:2161-2168.
103. Sileno AP, Brandt GC, Spann BM, Quay SC: Lower mean weight after 14 days intravenous administration peptide YY3-36 (PYY3-36) in rabbits. Int J Obes (Lond) 2006;30:68-72.
104. Halford JC: Obesity drugs in clinical development. Curr Opin Investig Drugs 2006;7:312-318.
105. Date Y, Kojima M, Hosoda H, Sawaguchi A, Mondal MS, Suganuma T, Matsukura S, Kangawa K, Nakazato M: Ghrelin, a novel growth-hormone- releasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans. Endocrinology 2000;141:4255-4261.
106. Gutierrez JA, Solenberg PJ, Perkins DR, Willency JA, Knierman MD, Jin Z, Witcher DR, Luo S, Onyia JE, Hale JE: Ghrelin octanoylation mediated by an orphan lipid transferase. Proc Natl Acad Sci U S A 2008;105:6320-6325.
107. 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.
108. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K: Ghrelin is a novel growth hormone releasing acylated peptide from stomach. Nature 1999;402:656-660.
109. Willesen MG, Kristensen P, Romer J: Co-localization of growth hormone secretagogue receptor and NPY mRNA in the arcuate nucleus of the rat. Neuroendocrinology 1999;70:306-316.
110. 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.
111. Cummings DE, Shannon MH: Roles for ghrelin in the regulation of appetite and body weight. Arch Surg 2003;138:389.
112. Tschöp M, Smiley DL, Heiman ML: Ghrelin induces adiposity in rodents. Nature 2000;407:908- 913.
113. Wren AM, Seal LJ, Cohen MA, Brynes AE, Frost GS, Murphy KG, Dhillo WS, Ghatei MA, Bloom SR: Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab 2001;86:5992.
114. Sun Y, Wang P, Zheng H, Smith RG: Ghrelin stimulation of growth hormone release and appetite is mediated through the growth hormone secretagogue receptor. Proc Natl Acad Sci U S A 2003;101:4679-4684.
115. Toshinai K, Yamaguchi H, Sun Y, Smith RG, Yamanaka A, Sakurai T, Date Y, Mondal MS, Shimbara T, Kawagoe T, Murakami N, Miyazato M, Kangawa K, Nakazato M: Des-acyl ghrelin induces food intake by a mechanism independent of the growth hormone secretagogue receptor. Endocrinology 2006;147:2306-2314.
116. Theander-Carrillo C, Wiedmer P, Cettour-Rose P, Nogueiras R, Perez-Tilve D, Pfluger P, Castaneda TR, Muzzin P, Schürmann A, Szanto I, Tschöp MH, Rohner-Jeanrenaud F: Ghrelin action in the brain controls adipocyte metabolism. J Clin Invest 2006;116:1983-1993.
117. Arvat E, Maccario M, Di Vito L, Broglio F, Benso A, Gottero C, Papotti M, Muccioli G, Dieguez C, Casanueva FF, Deghenghi R, Camanni F, Ghigo E: Endocrine activities of ghrelin, a natural growth hormone secretagogue (GHS), in humans: comparison and interactions with hexarelin, a nonnatural peptidyl GHS, and GH-releasing hormone. J Clin Endocrinol Metab 2001;86:1169-1174.
118. Depoortere I, De Winter B, Thijs T, De Man J, Pelckmans P, Peeters T: Comparison of the gastroprokinetic effects of ghrelin, GHRP-6 and motilin in rats in vivo and in vitro. Eur J Pharmacol 2005;515:160-168.
119. Isgaard J, Barlind A, Johansson I: Cardiovascular effects of ghrelin and growth hormone secretagogues. Cardiovasc Hematol Disord Drug Targets 2008;8:133-137.
120. Tannous dit El Khoury D, Obeid O, Azar ST, Hwalla N: Variations in postprandial ghrelin status following ingestion of high-carbohydrate, high-fat, and high-protein meals in males. Ann Nutr Metab 2006;50:260-269.
121. Cummings DE, Weigle DS, Frayo RS, Breen PA, Ma MK, Dellinger EP, Purnell JQ: Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med 2002;346:1623-1630.
122. Tschöp M, Wawarta R, Riepl RL, Friedrich S, Bidlingmaier M, Landgraf R, Folwaczny C: Postprandial decrease of circulating human ghrelin levels. J Endocrinol Invest 2001;24:RC19-21.
123. Drazen DL, Vahl TP, D'Alessio DA, Seeley RJ, Woods SC: Effects of a fixed meal pattern on ghrelin secretion: evidence for a learned response independent of nutrient status. Endocrinology 2006;147:23-30.
124. Shintani M, Ogawa Y, Ebihara K, Aizawa-Abe M, Miyanaga F, Takaya K, Hayashi T, Inoue G, Hosoda K, Kojima M, Kangawa K, Nakao K: Ghrelin, an endogenous growth hormone secretagogue, is a novel orexigenic peptide that antagonizes leptin action through the activation of hypothalamic neuropeptide Y/Y1 receptor pathway. Diabetes 2001;50:227-232.
125. Banks WA, Tschöp M, Robinson SM, Heiman ML: Extent and direction of ghrelin transport across the blood-brain barrier is determined by its unique primary structure. J Pharmacol Exp Ther 2002;302:822-827.
126. Date Y, Murakami N, Toshinai K, Matsukura S, Niijima A, Matsuo H, Kangawa K, Nakazato M: The role of the gastric afferent vagal nerve in ghrelin- induced feeding and growth hormone secretion in rats. Gastroenterology 2002;123:1120-1128.
127. Yasuda T, Masaki T, Kakuma T, Yoshimatsu H: Centrally administered ghrelin suppresses sympathetic nerve activity in brown adipose tissue of rats. Neurosci Lett 2003;349:75-78.
128. Lawrence CB, Snape AC, Baudoin FM, Luckman SM: Acute central ghrelin and GH secretagogues induce feeding and activate brain appetite centers. Endocrinology 2002;143:155-162.
129. Cummings DE, Foster KE: Ghrelin-leptin tango in body-weight regulation. Gastroenterology 2003;124:1532-1535.
130. Kohno D, Nakata M, Maekawa F, Fujiwara K, Maejima Y, Kuramochi M, Shimazaki T, Okano H, Onaka T, Yada T: Leptin suppresses ghrelininduced activation of neuropeptide Y neurons in the arcuate nucleus via phosphatidylinositol 3-kinase- and phosphodiesterase 3-mediated pathway. Endocrinology 2007;148:2251-2263.
131. Saad MF, Bernaba B, Hwu CM, Jinagouda S, Fahmi S, Kogosov E, Boyadjian R: Insulin regulates plasma ghrelin concentration. J Clin Endocrinol Metab 2002;87:3997-4000.
132. McLaughlin T, Abbasi F, Lamendola C, Frayo RS, Cummings DE: Plasma ghrelin concentrations are decreased in insulin-resistant obese adults relative to equally obese insulin-sensitive controls. J Clin Endocrinol Metab 2004;89:1630-1635.
133. Paik KH, Jin DK, Song SY, Lee JE, Ko SH, Song SM, Kim JS, Oh YJ, Kim SW, Lee SH, Kim SH, Kwon EK, Choe YH: Correlation between fasting plasma ghrelin levels and age, body mass index (BMI), BMI percentiles, and 24-hour plasma ghrelin profiles in Prader-Willi syndrome. J Clin Endocrinol Metab 2004;89:3885-3889.
134. Tschöp M, Weyer C, Tataranni PA, Devanarayan V, Ravussin E, Heiman ML: Circulating ghrelin levels are decreased in human obesity. Diabetes 2001;50:707-709.
135. Cremonini F, Camilleri M, Vazquez Roque M, McKinzie S, Burton D, Baxter K, Zinsmeister AR: Obesity does not increase effects of synthetic ghrelin on human gastric motor functions. Gastroenterology 2006;131:1431-1439.
136. Morínigo R, Casamitjana R, Moizé V, Lacy AM, Delgado S, Gomis R, Vidal J: Short-term effects of gastric bypass surgery on circulating ghrelin levels. Obes Res 2004;12:1108-1116.
137. Neary NM, Small CJ, Wren AM, Lee JL, Druce MR, Palmieri C, Frost GS, Ghatei MA, Coombes RC, Bloom SR: Ghrelin increases energy intake in cancer patients with impaired appetite: acute, randomized, placebo-controlled trial. J Clin Endocrinol Metab 2004;89:2832-2836.
138. Muccioli G, Tschöp M, Papotti M, Deghenghi R, Heiman M, Ghigo E: Neuroendocrine and peripheral activities of ghrelin: implications in metabolism and obesity. Eur J Pharmacol 2002;440:235-254.
139. Xin Z, Serby MD, Zhao H, Kosogof C, Szczepankiewicz BG, Liu M, Liu B, Hutchins CW, Sarris KA, Hoff ED, Falls HD, Lin CW, Ogiela CA, Collins CA, Brune ME, Bush EN, Droz BA, Fey TA, Knourek-Segel VE, Shapiro R, Jacobson PB, Beno DW, Turner TM, Sham HL, Liu G: Discovery and pharmacological evaluation of growth hormone secretagogue receptor antagonists. J Med Chem 2006;49:4459-4469.
140. Moulin A, Ryan J, Martinez J, Fehrentz JA: Recent developments in ghrelin receptor ligands. ChemMedChem 2007;2:1242-1259.