Strader AD, Woods SC

Idioma: Español
Referencias bibliográficas: 276
Paginas: 439-457
Archivo PDF: 162.32 Kb.

FRAGMENTO

A pesar de las espectaculares fluctuaciones en la ingesta calórica, los animales mantienen un peso corporal muy estable. La razón es que la ingesta y el gasto energéticos guardan un equilibrio preciso. La regulación a largo plazo del balance energético depende de la coordinación e interpretación de señales como las que envían insulina y leptina para indicar la presencia de reservas energéticas a largo plazo, así como de señales de corto plazo, relacionadas con las comidas, como las generadas por colecistoquinina (CCK). En los últimos 30 años nuestro conocimiento de las señales de corto plazo ha aumentado en forma dramática. A lo largo del eje cefalocaudal del sistema gastrointestinal, diferentes células enteroendocrinas responden a la estimulación tanto mecánica como química. La liberación de hormonas asociadas con las comidas depende de la concentración y composición de los nutrientes ingeridos. Las señales enviadas se transmiten neuralmente a través de haces aferentes del vago o por vía humoral en forma de ligandos circulantes para receptores específicos en el sistema nervioso periférico y central. Estas señales son interpretadas por el SNC y se manifiestan por modificaciones conductuales de la alimentación. Esta revisión presenta un análisis de la literatura pasada y actual que sustenta la participación de las hormonas intestinales y sus funciones como mediadores de la saciedad. Se presentan evidencias de estudios farmacológicos y fisiológicos tanto en humanos como en roedores, junto con una breve sección que describe el conocimiento adquirido a partir del empleo de modelos murinos con ablación genética selectiva o knockout. Por último, se revisará la contribución de las hormonas de la saciedad como probables mediadores de la efectividad observada después de la cirugía de la obesidad. Aun cuando tradicionalmente se les ha considerado como señales de corto plazo relacionadas con las comidas, la secreción hormonal aumentada, crónica, y la señalización resultante de la reconstrucción intestinal, como se observa en la cirugía de derivación gástrica, muy probablemente contribuyen a la mayor eficacia de la cirugía en el tratamiento de la obesidad.

REFERENCIAS (EN ESTE ARTÍCULO)

1. Woods SC, Seeley RJ, Porte DJ, Schwartz MW. Signals that regulate food intake and energy homeostasis. Science 1998; 280: 1378-83.

2. Woods SC, Schwartz MW, Baskin DG, Seeley RJ. Food intake and the regulation of body weight. Annu Rev Psychol 2000; 51: 255-77.

3. Schwartz MW, Woods SC, Porte DJ, Seeley RJ, Baskin DG. Central nervous system control of food intake. Nature 2000; 404: 661-71.

4. Seeley RJ, Woods SC. Monitoring of stored and available fuel by the CNS: implications for obesity. Nat Rev Neurosci 2003; 4: 901-9.

5. Woods SC. Gastrointestinal satiety signals I. An overview of gastrointestinal signals that influence food intake. Am J Physiol 2004; 286: G7-G13.

6. Bayliss WM, Starling EH. The mechanism of pancreatic secretion. J Physiol 1902; 28: 325.

7. Edkins JS. On the chemical mechanism of gastric acid secretion. Proc R Soc Lond B Biol Sci 1905; 76: 376-90.

8. Jorpes JE, Mutt V. Secretin, pancreozymin, and cholecystokinin: their preparation and properties. Gastroenterology 1959; 36: 377-85.

9. Emson PC, Hunt SP, Rehfeld JF, Golterman N, Fahrenkrug J. Cholecystokinin and vasoactive intestinal polypeptide in the mammalian CNS: distribution and possible physiological roles. Adv Biochem Psychopharmacol 1980; 22: 63-74.

10. Adamo M, Raizada MK, LeRoith D. Insulin and insulin-like growth factor receptors in the nervous system. Mol Neurobiol 1989; 3: 71-100.

11. Figlewicz DP, Lacour F, Sipols A, Porte D Jr, Woods SC. Gastro-enteropancreatic (GEP) peptides and the central nervous system. Ann Rev Physiol 1987; 49: 383-95.

12. Moran TH, Ladenheim EE, Schwartz GJ. Within-meal gut feedback signaling. Int J Obes Relat Metab Dis 2001; 25 (Suppl 5): S39-S41.

13. Moran TH, Kinzig KP. Gastrointestinal satiety signals II. Cholecystokinin. Am J Physiol 2004; 286: G183-G188.

14. Antin J, Gibbs J, Holt J, Young RC, Smith GP. Cholecystokinin elicits the complete behavioral sequence of satiety in rats. J Comp Physiol Psychol 1975; 89: 784-90.

15. Smith GP, Gibbs J. The development and proof of the cholecys-tokinin hypothesis of satiety. In: Dourish CT, Cooper SJ, Iversen SD, Iversen LL (eds.). Multiple cholecystokinin receptors in the CNS. Oxford: Oxford University Press; 1992, p. 166-82.

16. Strubbe JH, van Dijk G. The temporal organization of ingestive behaviour and its interaction with regulation of energy balance. Neurosci Biobehav Rev 2002; 26: 485-498.

17. Kissileff HR, Pi-Sunyer FX, Thornton J, Smith GP. Cholecystokinin decreases food intake in man. Am J Clin Nutr 1981; 34: 154-60.

18. Muurahainen NE, Kissileff HR, Pi-Sunyer FX. Intravenous infusion of bombesin reduces food intake in humans. Am J Physiol 1993; 264: R350-R354.

19. Muurahainenn N, Kissileff HR, Derogatis AJ, Pi-Sunyer FX. Effects of cholecystokinin-octapeptide (CCK-8) on food intake and gastric emptying in man. Physiol Behav 1988; 44: 644-9.

20. Pi-Sunyer X, Kissileff HR, Thornton J, Smith GP. C-terminal octapeptide of cholecystokinin decreases food intake in obese men. Physiol Behav 1982; 29: 627-30.

21. Cummings DE, Shannon MH. Roles for ghrelin in the regulation of appetite and body weight. Arch Surg 2003; 138: 389-96.

22. Tschöp M, Smiley DL, Heiman ML. Ghrelin induces adiposity in rodents. Nature 2000; 407: 908-13.

23. Roth KA, Gordon JI. Spatial differentiation of the intestinal epithelium: analysis of enteroendocrine cells containing immunoreactive serotonin, secretin, and substance P in normal and transgenic mice. Proc Natl Acad Sci USA 1990; 87: 6408-12.

24. Lundgren O. Interface between the intestinal environment and the nervous system. Gut 2004; 53(Suppl. 2): 16-18.

25. Mei N. Intestinal chemosensitivity. Physiol Rev 1985; 65: 211-37.

26. Read N, French S, Cunningham K. The role of the gut in regulating food intake in man. Nutr Rev 1994; 52: 1-10.

27. Raybould HE. Nutrient tasting and signaling mechanisms in the gut. I. Sensing of lipid by the intestinal mucosa. Am J Physiol 1999; 277: G751-G755.

28. Roberge JN, Brubaker PL. Secretion of proglucagon-derived peptides in response to intestinal luminal nutrients. Endocrinology 1991; 128: 3169-174.

29. Tso P, Chen Q, Fujimoto K, Fukagawa K, Sakata T. Apolipoprotein A-IV: a circulating satiety signal produced by the small intestine. Obes Res 1995; 3(Suppl. 5): S689-S695.

30. Layer P, Holst JJ, Grandt D, Goebell H. Ileal release of glucagon-like peptide-1 (GLP-1). Association with inhibition of gastric acid secretion in humans. Dig Dis Sci 1995; 40: 1074-82.

31. Pironi L, Stanghellini V, Miglioli M, Corinaldesi R, De Giorgio R, Ruggeri E, Tosetti C, Poggioli G, Morselli Labate AM, Monetti N, et al. Fat-induced ileal brake in humans: a dose-dependent phenomenon correlated to the plasma levels of peptide YY. Gastroenterology 1993; 105:733-39.

32. Xiao Q, Boushey RP, Drucker DJ, Brubaker PL. Secretion of the intestinotropic hormone glucagon-like peptide 2 is differentially regulated by nutrients in humans (comments). Gastroenterology 1999; 117: 99-105.

33. Holzer P, Michl T, Danzer M, Jocic M, Schicho R, Lippe IT. Surveillance of the gastrointestinal mucosa by sensory neurons. J Physiol Pharmacol 2001; 52: 505-21.

34. Reidelberger RD. Cholecystokinin and control of food intake. J Nutr 1994; 124: S1327-S1333.

35. Beck B. Gastric inhibitory polypeptide: a gut hormone with ana-bolic functions. J Mol Endocrinol 1989; 2: 169-74.

36. Liddle RA, Goldfine ID, Rosen MS, Taplitz RA, Williams JA. Cholecystokinin bioactivity in human plasma. Molecular forms, responses to feeding, and relationship to gallbladder contraction. J Clin Invest 1985; 75: 1144-52.

37. Chey WY, Chang T. Neural hormonal regulation of exocrine pancreatic secretion. Pancreatology 2001; 1: 320-35.

38. Brubaker PL, Izzo A, Hill M, Drucker DJ. Intestinal function in mice with small bowel growth induced by glucagon-like peptide-2. Am J Physiol 1997; 272: E1050-E1058.

39. Buyse M, Aparicio T, Guilmeau S, Goiot H, Sobhani I, Bado A. Paracrine actions of the stomach-derived leptin. Med Sci (Paris) 2004; 20: 183-8.

40. Holle GE, Dietl J, Demir I. Influence of the intramural innervation on the morphogenesis of the enteroendocrine cells and the genetic construct involved (review). Int J Mol Med 2003; 11: 275-85.

41. Moran TH, Norgren R, Crosby RJ, McHugh PR. Central and peripheral vagal transport of cholecystokinin binding sites occurs in afferent fibers. Brain Res 1990; 526: 95-102.

42. Rinaman L, Hoffman GE, Dohanics J, Le WW, Stricker EM, Verbalis JG. Cholecystokinin activates catecholaminergic neu-rons in the caudal medulla that innervate the paraventricular nucleus of the hypothalamus in rats. J Comp Neurol 1995; 360: 246-56.

43. Grill HJ, Smith GP. Cholecystokinin decreases sucrose intake in chronic decerebrate rats. Am J Physiol 1988; 254: R853-R856.

44. Grill HJ, Kaplan JM. The neuroanatomical axis for control of energy balance. Front Neuroendocrinol 2002; 23: 2-40.

45. Seeley RJ, Grill HJ, Kaplan JM. Neurological dissociation of gastrointestinal and metabolic contributions to meal size control. Behav Neurosci 1994; 108: 347-52.

46. Berthoud HR. Multiple neural systems controlling food intake and body weight. Neurosci Biobehav Rev 2002; 26: 393-428.

47. Powley TL, Phillips RJ. Musings on the wanderer: what’s new in our understanding of vago-vagal reflexes? I. Morphology and topography of vagal afferents innervating the GI tract. Am J Physiol Gastrointest Liver Physiol 2002; 283: G1217-G1225.

48. Deutsch JA. The role of the stomach in eating. Am J Clin Nutr 1985; 42: 1040-3.

49. Phillips RJ, Powley TL. Gastric volume rather than nutrient content inhibits food intake. Am J Physiol 1996; 271: R766-R769.

50. Davison JS, Clarke GD. Mechanical properties and sensitivity to CCK of vagal gastric slowly adapting mechanoreceptors. Am J Physiol 1988; 255: G55-G61.

51. Kaplan JM, Moran TH. Gastrointestinal signaling in the control of food intake. In: Stricker EM, Woods SC (eds.). Handbook of behavioral neurobiology. Neurobiology of food and fluid intake, 2nd Ed. Vol. 14. New York: Kluwer Academic; 2004, p. 275-305.

52. Polak JM, Bloom SR, Rayford PL, Pearse AG, Buchan AM, Thompson JC. Identification of cholecystokinin-secreting cells. Lancet 1975; 2: 1016-18.

53. Beinfeld MC, Meyer DK, Brownstein MJ. Cholecystokinin in the central nervous system. Peptides 1981; 2(Suppl 2): 77-9.

54. Wank SA, Harkins R, Jensen RT, Shapira H, de Weerth A, Slattery T. Purification, molecular cloning, and functional expression of the cholecystokinin receptor from rat pancreas. Proc Natl Acad Sci USA 1992; 89: 3125-9.

55. Wank SA, Pisegna JR, de Weerth A. Brain and gastrointestinal cholecystokinin receptor family: structure and functional expression. Proc Natl Acad Sci USA 1992; 89: 8691-5.

56. Moran TH, Robinson PH, Goldrich MS, McHugh PR. Two brain cholecystokinin receptors: implications for behavioral actions. Brain Res 1986; 362: 175-9.

57. Herranz R. Cholecystokinin antagonists: pharmacological and therapeutic potential. Med Res Rev 2003; 23: 559-605.

58. Douglas BR, Jansen JB, de Jong AJ, Lamers CB. Effect of various triglycerides on plasma cholecystokinin levels in rats. J Nutr 1990; 120: 686-90.

59. Lewis LD, Williams JA. Regulation of cholecystokinin secretion by food, hormones, and neural pathways in the rat. Am J Physiol 1990; 258: G512-G518.

60. Schwartz GJ, Moran TH, White WO, Ladenheim EE. Relation-ships between gastric motility and gastric vagal afferent responses to CCK and GRP in rats differ. Am J Physiol 1997; 272: R1726-R1733.

61. Grider JR. Role of cholecystokinin in the regulation of gastrointestinal motility. J Nutr 1994; 124: 1334S-1339S.

62. Gibbs J, Young RC, Smith GP. Cholecystokinin decreases food intake in rats. J Comp Physiol Psychol 1973; 84: 488-95.

63. Figlewicz DP, Stein LJ, West D, Porte D Jr, Woods SC. Intracisternal insulin alters sensitivity to CCK-induced meal suppression in baboons. Am J Physiol 1986; 250: R856-R860.

64. Zhang DM, Bula W, Stellar E. Brain cholecystokinin as a satiety peptide. Physiol Behav 1986; 36: 1183-6.

65. Della-Fera MA, Baile CA. CCK-octapeptide injected in CSF decreases meal size and daily food intake in sheep. Peptides 1980; 1: 51-4.

66. Houpt TR. The sites of action of cholecystokinin in decreasing meal size in pigs. Physiol Behav 1983; 31: 693-8.

67. Kissileff HR, Pi-Sunyer FX, Thornton J, Smith GP. C-terminal octapeptide of cholecystokinin decreases food intake in man. Am J Clin Nutr 1981; 34: 154-60.

68. Snapir N, Glick Z. Cholecystokinin and meal size in the domestic fowl. Physiol Behav 1978; 21: 1051-2.

69. Gibbs J, Smith GP. Cholecystokinin and satiety in rats and rhesus monkeys. Am J Clin Nutr 1977; 30: 758-61.

70. Figlewicz DP, Sipols AJ, Green P, Porte D Jr, Woods SC. IVT CCK-8 is more effective than IV CCK-8 in decreasing meal size in the baboon. Brain Res Bull 1989; 22: 849-52.

71. Beglinger C, Degen L, Matzinger D, D’Amato M, Drewe J. Loxiglumide, a CCK-A receptor antagonist, stimulates calorie intake and hunger feelings in humans. Am J Physiol 2001; 280: R1149-R1154.

72. Hewson G, Leighton GE, Hill RG, Hughes J. The cholecystokinin receptor antagonist L364,718 increases food intake in the rat by attenuation of endogenous cholecystokinin. Br J Pharmacol 1988; 93: 79-84.

73. Moran TH, Ameglio PJ, Peyton HJ, Schwartz GJ, McHugh PR. Blockade of type A, but not type B, CCK receptors postpones satiety in rhesus monkeys. Am J Physiol 1993; 265: R620-R624.

74. Reidelberger RD, O’Rourke MF. Potent cholecystokinin antagonist L-364,718 stimulates food intake in rats. Am J Physiol 1989; 257: R1512-R1518.

75. Crawley JN, Beinfeld MC. Rapid development of tolerance to the behavioural actions of cholecystokinin. Nature 1983; 302: 703-6.

76. West DB, Fey D, Woods SC. Cholecystokinin persistently suppresses meal size but not food intake in free-feeding rats. Am J Physiol 1984; 246: R776-R787.

77. West DB, Greenwood MRC, Marshall KA, Woods SC. Lithium chloride, cholecystokinin and meal patterns: evidence the cholecystokinin suppresses meal size in rats without causing malaise. Appetite 1987; 8: 221-7.

78. Tsunoda Y, Yao H, Park J, Owyang C. Cholecystokinin synthesizes and secretes leptin in isolated canine gastric chief cells. Biochem Biophys Res Commun 2003; 310: 681-4.

79. Barrachina MD, Martinez V, Wang L, Wei JY, Tache Y. Synergistic interaction between leptin and cholecystokinin to reduce short term food intake in lean mice. Proc Natl Acad Sci USA 1997; 94: 10455-60.

80. Matson CA, Reid DF, Cannon TA, Ritter RC. Cholecystokinin and leptin act synergistically to reduce body weight. Am J Physiol 2000; 278: R882-R890.

81. Matson CA, Wiater MF, Kuijper JL, Weigle DS. Synergy between leptin and cholecystokinin (CCK) to control daily caloric intake. Peptides 1997; 18: 1275-8.

82. Emond M, Schwartz GJ, Ladenheim EE, Moran TH. Central leptin modulates behavioral and neural responsivity to CCK. Am J Physiol 1999; 276: R1545-R1549.

83. Figlewicz DP, Sipols AJ, Seeley RJ, Chavez M, Woods SC, Porte DJ. Intraventricular insulin enhances the meal-suppressive efficacy of intraventricular cholecystokinin octapeptide in the baboon. Behav Neurosci 1995; 109: 567-9.

84. Riedy CA, Chavez M, Figlewicz DP, Woods SC. Central insulin enhances sensitivity to cholecystokinin. Physiol Behav 1995; 58: 755-60.

85. Niswender KD, Schwartz MW. Insulin and leptin revisited: adiposity signals with overlapping physiological and intracellular signaling capabilities. Front Neuroendocrinol 2003; 24: 1-10.

86. Kulkosky PJ, Breckenridge C, Krinsky R, Woods SC. Satiety elicited by the C-terminal octapeptide of cholecystokinin-pancreozymin in normal and VMH-lesioned rats. Behav Biol 1976; 18: 227-34.

87. Moos AB, McLaughlin CL, Baile CA. Effects of CCK on gastrointestinal function in lean and obese Zucker rats. Peptides 1982; 3: 619-22.

88. Funakoshi A, Miyasaka K, Shinozaki H, Masuda M, Kawanami T, Takata Y, Kono A. An animal model of congenital defect of gene expression of cholecystokinin (CCK)-A receptor. Bichem Biophys Res Commun 1995; 210: 787-96.

89. Bi S, Moran TH. Actions of CCK in the controls of food intake and body weight: lessons from the CCK-A receptor deficient OLETF rat. Neuropeptides 2002; 36: 171-81.

90. Moran TH, Katz LF, Plata-Salaman CR, Schwartz GJ. Disordered food intake and obesity in rats lacking cholecystokinin A receptors. Am J Physiol 1998; 274: R618-R625.

91. Lorenz DN, Goldman SA. Vagal mediation of the cholecystokinin satiety effect in rats. Physiol Behav 1982; 29: 599-604.

92. Moran TH, Baldessarini AR, Salorio CF, Lowery T, Schwartz GJ. Vagal afferent and efferent contributions to the inhibition of food intake by cholecystokinin. Am J Physiol 1997; 272: R1245-R1251.

93. Edwards GL, Ladenheim EE, Ritter RC. Dorsomedial hindbrain participation in cholecystokinin-induced satiety. Am J Physiol 1986; 251: R971–R977.

94. Fan W, Ellacott KL, Halatchev IG, Takahashi K, Yu P, Cone RD. Cholecystokinin-mediated suppression of feeding involves the brainstem melanocortin system. Nat Neurosci 2004; 7: 335-6.

95. Gibbs J, Fauser DJ, Rowe EA, Rolls ET, Maddison SP. Bombesin suppresses feeding in rats. Nature 1979; 282: 208-10.

96. Gibbs J, Guss JL. Bombesin-like peptides and satiety. Appetite 1995; 24: 257.

97. Ladenheim EE, Wirth KE, Moran TH. Receptor subtype mediation of feeding suppression by bombesin-like peptides. Pharmacol Biochem Behav 1996; 54: 705-11.

98. Stein LJ, Woods SC. Gastrin releasing peptide reduces meal size in rats. Peptides 1982; 3: 833-5.

99. Ladenheim EE, Jensen RT, Mantey SA, Moran TH. Distinct distributions of two bombesin receptor subtypes in the rat central nervous system. Brain Res 1992; 593: 168-78.

100. Minamino N, Kangawa K, Matsuo H. Neuromedin B: a novel bombesin-like peptide identified in porcine spinal cord. Biochem Biophys Res Commun 1983; 114: 541-8.

101. Ladenheim EE, Taylor JE, Coy DH, Carrigan TS, Wohn A, Moran TH. Caudal hindbrain neuromedin B-preferring receptors participate in the control of food intake. Am J Physiol 1997; 272: R433-R437.

102. Ladenheim EE, Hampton LL, Whitney AC, White WO, Battey JF, Moran TH. Disruptions in feeding and body weight control in gastrin-releasing peptide receptor deficient mice. J Endocrinol 2002; 174: 273-81.

103. Miesner J, Smith GP, Gibbs J, Tyrka A. Intravenous infusion of CCKA-receptor antagonist increases food intake in rats. Am J Physiol 1992; 262: R216-R219.

104. Rushing PA, Gibbs J, Geary N. Brief, meal-contingent infusions of gastrin-releasing peptide 1-27 and neuromedin B-10 in spontaneous feeding in rats. Physiol Behav 1996; 60: 1501-4. 186 Strader and Woods Gastroenterology Vol. 128, No.1.

105. Rushing PA, Gibbs J. Prolongation of intermeal interval by gastrin-releasing peptide depends upon time of delivery. Peptides 1998; 19: 1439-42.

106. Rushing PA, Henderson RP, Gibbs J. Prolongation of the post-prandial intermeal interval by gastrin-releasing peptide 1-27 in spontaneously feeding rats. Peptides 1998; 19: 175-7.

107. Stuckey JA, Gibbs J, Smith GP. Neural disconnection of gut from brain blocks bombesin-induced satiety. Peptides 1985; 6: 1249-52.

108. Thaw AK, Smith JC, Gibbs J. Mammalian bombesin-like peptides extend the intermeal interval in freely feeding rats. Physiol Behav 1998; 64: 425-8.

109. Ludvik B, Kautzky-Willer A, Prager R, Thomaseth K, Pacini G. Amylin: history and overview. Diabetic Med 1997; 14(Suppl 2): S9-S13.

110. Chance WT, Balasubramaniam A, Zhang FS, Wimalawansa SJ, Fischer JE. Anorexia following the intrahypothalamic administration of amylin. Brain Res 1991; 539: 352-4.

111. Lutz TA, Del Prete E, Scharrer E. Reduction of food intake in rats by intraperitoneal injection of low doses of amylin. Physiol Behav 1994; 55: 891-5.

112. Lutz TA, Geary N, Szabady MM, Del Prete E, Scharrer E. Amylin decreases meal size in rats. Physiol Behav 1995; 58: 1197-1202.

113. Rushing PA, Hagan MM, Seeley RJ, Lutz TA, Woods SC. Amylin: a novel action in the brain to reduce body weight. Endocrinology 2000; 141: 850-3.

114. Lutz TA, Althaus J, Rossi R, Scharrer E. Anorectic effect of amylin is not transmitted by capsaicin-sensitive nerve fibers. Am J Physiol 1998; 274: R1777–R1782.

115. Lutz TA, Senn M, Althaus J, Del Prete E, Ehrensperger F, Scharrer E. Lesion of the area postrema/nucleus of the solitary tract (AP/NTS) attenuates the anorectic effects of amylin and calcitonin generelated peptide (CGRP) in rats. Peptides 1998; 19: 309-17.

116. Lutz TA, Del Prete E, Scharrer E. Subdiaphragmatic vagotomy does not influence the anorectic effect of amylin. Peptides 1995; 16: 457-62.

117. Rushing PA, Lutz TA, Seeley RJ, Woods SC. Amylin and insulin interact to reduce food intake in rats. Horm Metab Res 2000; 32: 62-5.

118. Holst JJ. Enteroglucagon. Annu Rev Physiol 1997; 59: 257-71.

119. D’Alessio DA, Kahn SE, Leusner CR, Ensinck JW. Glucagon-like peptide 1 enhances glucose tolerance both by stimulation of insulin release and by increasing insulin-independent glucose disposal. J Clin Invest 1994; 99: 2263-6.

120. D’Alessio D. Peptide hormone regulation of islet cells. Horm Metab Res 1997; 29: 297-300.

121. Drucker DJ. Biological actions and therapeutic potential of the glucagon-like peptides. Gastroenterol 2002; 122: 531-44.

122. Hermann C, Goke R, Richter G, Fehman HC, Arnbold R, Goke B. Glucagon-like peptide-1 and glucose-dependent insulin-releas-ing polypeptide plasma levels in response to nutrients. Digestion 1995; 56: 117-26.

123. Kieffer TJ, McIntosh CH, Pederson RA. Degradation of glucose-dependent insulinotropic polypeptide and truncated glucagon-like peptide 1 in vitro and in vivo by dipeptidyl peptidase IV. Endocrinology 1995; 136:3585-96.

124. Campos RV, Lee YC, Drucker DJ. Divergent tissue-specific and developmental expression of receptors for glucagon and glucagon-like peptide-1 in the mouse. Endocrinology 1994; 134: 2156-64.

125. Brubaker PL, Anini Y. Direct and indirect mechanisms regulating secretion of glucagon-like peptide-1 and glucagon-like peptide-2. Can J Physiol Pharmacol 2003; 81: 1005-12.

126. Qualmann C, Nauck MA, Holst JJ, Orskov C, Creutzfeldt W. Glucagon-like peptide 1 (7-36 amide) secretion in response to luminal sucrose from the upper and lower gut. A study using alpha-glucosidase inhibition (acarbose). Scand J Gastroenterol 1995; 30: 892-6.

127. Giralt M, Vergara P. Glucagonlike peptide-1 (GLP-1) participation in ileal brake induced by intraluminal peptones in rat. Dig Dis Sci 1999; 44: 322-9.

128. Nauck MA, Niedereichholz U, Ettler R, Holst JJ, Orskov C, Ritzel R, Schmiegel WH. Glucagon-like peptide-1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy hu-mans. Am Physiol Soc 1997: E981-E988.

129. Turton MD, O’Shea D, Gunn I, Beak SA, Edwards CM, Meeran K, Choi SJ, Taylor GM, Heath MM, Lambert PD, Wilding JP, Smith DM, Ghatei MA, Herbert J, Bloom SR. A role for glucagon-like peptide-1 in the central regulation of feeding (comments). Nature 1996; 379: 69-72.

130. Tang-Christensen M, Larsen PJ, Goke R, Fink-Jensen A, Jessop DS, Moller M, Sheikh SP. Central administration of GLP-1-(7-36) amide inhibits food and water intake in rats. Am J Physiol 1996; 271: R848-R856.

131. Donahey JC, van Dijk G, Woods SC, Seeley RJ. Intraventricular GLP-1 reduces short-but not long-term food intake or body weight in lean and obese rats. Brain Res 1998; 779: 75-83.

132. Naslund E, Gutniak M, Skogar S, Rossner S, Hellstrom PM. Glucagon-like peptide 1 increases the period of postprandial satiety and slows gastric emptying in obese men. Am J Clin Nutr 1998; 68: 525-30.

133. Gutzwiller JP, Goke B, Drewe J, Hildebrand P, Ketterer S, Hand-schin D, Winterhalder R, Conen D, Beglinger C. Glucagon-like peptide-1: a potent regulator of food intake in humans. Gut 1999; 44: 81-6.

134. Thiele TE, Van Dijk G, Campfield LA, Smith FJ, Burn P, Woods SC, Bernstein IL, Seeley RJ. Central infusion of GLP-1, but not leptin, produces conditioned taste aversions in rats. Am J Physiol 1997; 272: R726-R730.

135. van Dijk G, Thiele TE, Donahey JCK, Campfield LA, Smith FJ, Burn P, Bernstein IL, Woods SC, Seeley RJ. Central infusion of leptin and GLP-1-(7-36) amide differentially stimulate c-Fos-like immunoreactivity in the rat brain. Am J Physiol 1996; 271: R1096-R1100.

136. Shughrue PJ, Lane MV, Merchenthaler I. Glucagon-like peptide-1 receptor (GLP1-R) mRNA in the rat hypothalamus. Endocrinology 1996; 137: 5159-62.

137. Navarro M, Rodriguez de Fonseca F, Alvarez E, Chowen JA, Zueco JA, Gomez R, Eng J, Blazquez E. Colocalization of glucagon-like peptide-1 (GLP-1) receptors, glucose transporter GLUT-2, and glucokinase mRNAs in rat hypothalamic cells: evidence for a role of GLP-1 receptor agonists as an inhibitory signal for food and water intake. J Neurochem 1996; 67: 1982-91.

138. Hwa JJ, Ghibaudi L, Williams P, Witten MB, Tedesco R, Strader CD. Differential effects of intracerebroventricular glucagon-like peptide-1 on feeding and energy expenditure regulation. Peptides 1998; 19: 869-75.

139. Tang-Christensen M, Larsen PJ, Goke R, Fink-Jensen A, Jessop DS, Moller M, Sheikh SP. Central administration of GLP-1-(7-36) amide inhibits food and water intake in rats. Am J Physiol 1996; 271: R848-R856.

140. Tang-Christensen M, Vrang N, Larsen PJ. Glucagon-like peptide 1(7-36) amide’s central inhibition of feeding and peripheral inhibition of drinking are abolished by neonatal monosodium glutamate treatment. Diabetes 1998; 47: 530-7.

141. Kinzig KP, D’Alessio DA, Seeley RJ. The diverse roles of CNS GLP-1 in the control of food intake and the mediation of visceral illness. J Neurosci 2002; 22: 10470-6.

142. Larsen PJ, Tang-Christensen M, Jessop DS. Central administration of glucagon-like peptide-1 activates hypothalamic neuroen-docrine neurons in the rat. Endocrinology 1997; 138: 4445-55.

143. McMahon LR, Wellman PJ. Decreased intake of a liquid diet in nonfood-deprived rats following intra-PVN injections of GLP-1 (7-36) amide. Pharmacol Biochem Behav 1997; 58: 673-7.

144. McMahon LR, Wellman PJ. PVN infusion of GLP-1-(7-36) amide suppresses feeding but does not induce aversion or alter locomotion in rats. Am J Physiol 1998; 274: R23-R29.

145. Rinaman L. A functional role for central glucagon-like peptide-1 receptors in lithium chloride-induced anorexia. Am J Physiol 1999; 277: R1537-R1540.

146. van Dijk G, Thiele TE, Seeley RJ, Woods SC, Bernstein IL. Glucagon-like peptide-1 and satiety? Nature 1997; 385: 214.

147. Kinzig KP, D’Alessio DA, Herman JP, Sakai RR, Vahl TP, Figueredo HF, Murphy EK, Seeley RJ. CNS glucagon-like peptide-1 receptors mediate endocrine and anxiety responses to interoceptive and psychogenic stressors. J Neurosci 2003; 23: 6163-70.

148. Naslund E, Barkeling B, King N, Gutniak M, Blundell JE, Holst JJ, Rossner S, Hellstrom PM. Energy intake and appetite are suppressed by glucagon-like peptide-1 (GLP-1) in obese men. Int J Obes Relat Metab Disord 1999; 23: 304-11.

149. Toft-Nielsen MB, Madsbad S, Holst JJ. Continuous subcutaneous infusion of glucagon-like peptide 1 lowers plasma glucose and reduces appetite in type 2 diabetic patients. Diabetes Care 1999; 22: 1137-43.

150. Gutzwiller JP, Drewe J, Goke B, Schmidt H, Rohrer B, Lareida J, Beglinger C. Glucagon-like peptide-1 promotes satiety and reduces food intake in patients with diabetes mellitus type 2. Am J Physiol 1999; 276: R1541-R1544.

151. Delgado-Aros S, Kim DY, Burton DD, Thomforde GM, Stephens D, Brinkmann BH, Vella A, Camilleri M. Effect of GLP-1 on gastric volume, emptying, maximum volume ingested, and postprandial symptoms in humans. Am J Physiol 2002; 282: G424-G431.

152. Kastin AJ, Akerstrom V, Pan W. Interactions of glucagon-like peptide-1 (GLP-1) with the blood-brain barrier. J Mol Neurosci 2002; 18: 7-14.

153. Larsen PJ, Vrang N, Tang-Christensen M. Central pre-proglucagon derived peptides: opportunities for treatment of obesity. Curr Pharm Des 2003; 9: 1373-82.

154. Nauck MA. Glucagon-like peptide 1 (GLP-1): a potent gut hormone with a possible therapeutic perspective. Acta Diabetol 1998; 35: 117-29.

155. Eng J, Kleinman WA, Singh L, Singh G, Raufman JP. Isolation and characterization of exendin-4, an exendin-3 analogue, from Heloderma suspectum venom. Further evidence for an exendin receptor on dispersed acini from guinea pig pancreas. J Biol Chem 1992; 267: 7402-5.

156. Pohl M, Wank SA. Molecular cloning of the helodermin and exendin-4 cDNAs in the lizard. Relationship to vasoactive intes-tinal polypeptide/pituitary adenylate cyclase activating polypep-tide and glucagon-like peptide 1 and evidence against the existence of mammalian homologues. J Biol Chem 1998; 273: 9778-84.

157. Goke R, Fehmann HC, Linn T, Schmidt H, Krause M, Eng J, Goke B. Exendin-4 is a high potency agonist and truncated exendin-(9-39)-amide an antagonist at the glucagon-like peptide 1-(7-36)-amide receptor of insulin-secreting-cells. J Biol Chem 1993; 268: 19650-5.

158. Edwards CM, Stanley SA, Davis R, Brynes AE, Frost GS, Seal LJ, Ghatei MA, Bloom SR. Exendin-4 reduces fasting and postprandial glucose and decreases energy intake in healthy volunteers. Am J Physiol Endocrinol Metab 2001; 281: E155-E161.

159. Kolterman OG, Buse JB, Fineman MS, Gaines E, Heintz S, Bicsak TA, Taylor K, Kim D, Aisporna M, Wang Y, Baron AD. Synthetic exendin-4 (exenatide) significantly reduces postprandial and fasting plasma glucose in subjects with type 2 diabetes. J Clin Endocrinol Metab 2003; 88: 3082-9.

160. Szayna M, Doyle ME, Betkey JA, Holloway HW, Spencer RG, Greig NH, Egan JM. Exendin-4 decelerates food intake, weight gain, and fat deposition in Zucker rats. Endocrinology 2000; 141: 1936-41.

161. Al-Barazanji KA, Arch JR, Buckingham RE, Tadayyon M. Central exendin-4 infusion reduces body weight without altering plasma leptin in (fa/fa) Zucker rats (In Process Citation). Obes Res 2000; 8: 317-23.

162. Kirkegaard P, Moody AJ, Holst JJ, Loud FB, Olsen PS, Christiansen J. Glicentin inhibits gastric acid secretion in the rat. Nature 1982; 297: 156-7.

163. Dakin CL, Gunn I, Small CJ, Edwards CM, Hay DL, Smith DM, Ghatei MA, Bloom SR. Oxyntomodulin inhibits food intake in the rat. Endocrinology 2001; 142: 4244-50.

164. Dakin CL, Small CJ, Park AJ, Seth A, Ghatei MA, Bloom SR. Repeated ICV administration of oxyntomodulin causes a greater reduction in body weight gain than in pair-fed rats. Am J Physiol Endocrinol Metab 2002; 283: E1173-E1177.

165. Cohen MA, Ellis SM, Le Roux CW, Batterham RL, Park A, Patterson M, Frost GS, Ghatei MA, Bloom SR. Oxyntomodulin suppresses appetite and reduces food intake in humans. J Clin Endocrinol Metab 2003; 88: 4696-4701.

166. Drucker DJ. Glucagon-like peptide 2. Trends Endocrinol Metab 1999; 10: 153-6.

167. Jeppesen PB. Clinical significance of GLP-2 in short-bowel syndrome. J Nutr 2003; 133: 3721-4.

168. Warner BW. GLP-2 as therapy for the short-bowel syndrome. Gastroenterology 2001; 120: 1041-3.

169. Orskov C, Holst JJ, Knuhtsen S, Baldissera FG, Poulsen SS, Nielsen OV. Glucagon-like peptides GLP-1 and GLP-2, predicted products of the glucagon gene, are secreted separately from pig small intestine but not pancreas. Endocrinology 1986; 119: 1467-75.

170. Tang-Christensen M, Larsen PJ, Thulesen J, Romer J, Vrang N. The proglucagon-derived peptide, glucagon-like peptide-2, is a neurotransmitter involved in the regulation of food intake. Nat Med 2000; 6: 802-7.

171. Sorensen LB, Flint A, Raben A, Hartmann B, Holst JJ, Astrup A. No effect of physiological concentrations of glucagon-like peptide-2 on appetite and energy intake in normal weight subjects. Int J Obes Relat Metab Disord 2003; 27: 450-6.

172. Schmidt PT, Naslund E, Gryback P, Jacobsson H, Hartmann B, Holst JJ, Hellstrom PM. Peripheral administration of GLP-2 to humans has no effect on gastric emptying or satiety. Regul Pept 2003; 116: 21-5.

173. Geary N. Glucagon and the control of meal size. In: Smith GP (ed.). Satiation. From gut to brain. New York: Oxford University Press; 1998, p. 164-97.

174. Salter JM. Metabolic effects of glucagon in the Wistar rat. Am J Clin Nutr 1960; 8: 535-9.

175. Woods SC, Lotter EC, McKay LD, Porte D Jr. Chronic intracere-broventricular infusion of insulin reduces food intake and body weight of baboons. Nature 1979; 282: 503-5.

176. Geary N, Le Sauter J, Noh U. Glucagon acts in the liver to control spontaneous meal size in rats. Am J Physiol 1993; 264: R116-R122.

177. Le Sauter J, Noh U, Geary N. Hepatic portal infusion of glucagon antibodies increases spontaneous meal size in rats. Am J Physiol 1991; 261: R162-R165.

178. Langhans W, Zieger U, Scharrer E, Geary N. Stimulation of feeding in rats by intraperitoneal injection of antibodies to glucagon. Science 1982; 218: 894-6.

179. Adrian TE, Bacarese-Hamilton AJ, Smith HA, Chohan P, Manolas KJ, Bloom SR. Distribution and postprandial release of porcine peptide YY. J Endocrinol 1987; 113: 11-14.

180. Taylor RG, Beveridge DJ, Fuller PJ. Expression of ileal glucagon and peptide tyrosine-tyrosine genes. Response to inhibition of polyamine synthesis in the presence of massive small-bowel resection. Biochem J 1992; 286: 737-41.

181. 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: 151-9.

182. Mentlein R, Dahms P, Grandt D, Kruger R. Proteolytic processing of neuropeptide Y and peptide YY by dipeptidyl peptidase IV. Regul Pept 1993; 49: 133-44.

183. Larhammar D. Structural diversity of receptors for neuropeptide Y, peptide YY and pancreatic polypeptide. Regul Pept 1996; 65: 165-74.

184. Corp ES, Melville LD, Greenberg D, Gibbs J, Smith GP. Effect of fourth ventricular neuropeptide Y and peptide YY on ingestive and other behaviors. Am J Physiol 1990; 259: R317-R323.

185. 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: 650-4.

186. Ekblad E, Sundler F. Distribution of pancreatic polypeptide and peptide YY. Peptides 2002; 23: 251-61.

187. Greeley GH Jr, Hashimoto T, Izukura M, Gomez G, Jeng J, Hill FL, Lluis F, Thompson JC. A comparison of intraduodenally and intracolonically administered nutrients on the release of peptide-YY in the dog. Endocrinology 1989; 125: 1761-5.

188. Lin HC, Zhao XT, Wang L, Wong H. Fat-induced ileal brake in the dog depends on peptide YY. Gastroenterology 1996; 110: 1491-5.

189. Spiller RC, Trotman IF, Higgins BE, Ghatei MA, Grimble GK, Lee YC, Bloom SR, Misiewicz JJ, Silk DB. The ileal brake-inhibition of jejunal motility after ileal fat perfusion in man. Gut 1984; 25: 365-74.

190. Anini Y, Fu-Cheng X, Cuber JC, Kervran A, Chariot J, Roz C. Comparison of the postprandial release of peptide YY and proglucagon-derived peptides in the rat. Pflugers Arch 1999; 438: 299-306.

191. Hagan MM. Peptide YY: a key mediator of orexigenic behavior. Peptides 2002; 23: 377-82.

192. Hagan MM, Moss DE. Suppression of peptide YY-induced hy-perphagia by terbutaline. Pharmacol Biochem Behav 1993; 46: 679-81.

193. Nakajima M, Inui A, Teranishi A, Miura M, Hirosue Y, Okita M, Himori N, Baba S, Kasuga M. Effects of pancreatic polypeptide family peptides on feeding and learning behavior in mice. J Pharmacol Exp Ther 1994; 268: 1010-14.

194. Itoh E, Fujimiya M, Inui A. Thioperamide, a histamine H3 receptor antagonist, powerfully suppresses peptide YY-induced food intake in rats. Biol Psychiatry 1999; 45: 475-81.

195. Morley JE, Levine AS, Grace M, Kneip J. Peptide YY (PYY), a potent orexigenic agent. Brain Res 1985; 341: 200-3.

196. 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: 941-8.

197. Batterham RL, Le Roux CW, Cohen MA, Park AJ, Ellis SM, Patterson M, Frost GS, Ghatei MA, Bloom SR. Pancreatic polypeptide reduces appetite and food intake in humans. J Clin Endocrinol Metab 2003; 88: 3989-92.

198. Moran TH, Knipp S, Smedh U, Ladenheim EE. PYY(3-36) inhibits food intake and gastric emptying in monkeys. Appetite 2003; 40: 349.

199. Tschöp M, Castañeda TR, Joost HG, Thöne-Reineke C, Ortmann S, et al. Physiology: does gut hormone PYY(3-36) decrease food intake in rodents? Nature 2004; 430: 165-66.

200. Thöne-Reineke C, Ortman S, Castaneda T, Birringer M, Tschöp M. Effects of peripheral administration of PYY(3-36) on energy balance in mice. Philadelphia: In Endocrine Society, 2003.

201. Cone RD, Cowley MA, Butler AA, Fan W, Marks DL, Low MJ. The arcuate nucleus as a conduit for diverse signals relevant to energy homeostasis. Int J Obes Relat Metab Disord 2001; 25(Suppl 5): S63-S67.

202. Nonaka N, Shioda S, Niehoff ML, Banks WA. Characterization of blood-brain barrier permeability to PYY3-36 in mouse. J Pharmacol Exp Ther 2003; 306: 948-53.

203. Batterham RL, Bloom SR. The gut hormone peptide YY regulates appetite. Ann N Y Acad Sci 2003; 994: 162-8.

204. 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: 425-32.

205. Masuzaki H, Ogawa Y, Sagawa N, Hosoda K, Matsumoto T, Mise H, Nishimura H, Yoshimasa Y, Tanaka I, Mori T, Nakao K. Nonadipose tissue production of leptin: leptin as a novel placenta-derived hormone in humans. Nat Med 1997; 3: 1029-33.

206. Wang J, Liu R, Hawkins M, Barzilai N, Rossetti L. A nutrient-sensing pathway regulates leptin gene expression in muscle and fat. Nature 1998; 393: 684-8.

207. Bado A, Levasseur S, Attoub S, Kermorgant S, Laigneau JP, Bortoluzzi MN, Moizo L, Lehy T, Guerre-Millo M, Le Marchand-Brustel Y, Lewin MJ. The stomach is a source of leptin. Science 1998; 394: 90-3.

208. Cinti S, Matteis RD, Pico C, Ceresi E, Obrador A, Maffeis C, Oliver J, Palou A. Secretory granules of endocrine and chief cells of human stomach mucosa contain leptin. Int J Obes Relat Metab Disord 2000; 24: 789-93.

209. Cinti S, de Matteis R, Ceresi E, Pico C, Oliver J, Oliver P, Palou A, Obrador A, Maffeis C. Leptin in the human stomach. Gut 2001; 49: 155.

210. Sobhani I, Bado A, Vissuzaine C, Buyse M, Kermorgant S, Laigneau JP, Attoub S, Lehy T, Henin D, Mignon M, Lewin MJ. Leptin secretion and leptin receptor in the human stomach. Gut 2000; 47: 178-83.

211. Pico C, Sanchez J, Oliver P, Palou A. Leptin production by the stomach is up-regulated in obese (fa/fa) Zucker rats. Obes Res 2002; 10: 932-8.

212. Sobhani I, Buyse M, Goiot H, Weber N, Laigneau JP, Henin D, Soul JC, Bado A. Vagal stimulation rapidly increases leptin secretion in human stomach. Gastroenterology 2002; 122: 259-63.

213. Ahima RS, Prabakaran D, Mantzoros C, Qu D, Lowell B, Flier-Maratos E, Flier JS. Role of leptin in the neuroendocrine response to fasting. Nature 1996; 382: 250-2.

214. Elmquist JK, Elias CF, Saper CB. From lesions to leptin: hypothalamic control of food intake and body weight. Neuron 1999; 22: 221-32.

215. Tso P, Liu M, Kalogeris TJ, Thomson AB. The role of apolipoprotein A-IV in the regulation of food intake. Annu Rev Nutr 2001; 21: 231-54.

216. Liu M, Doi T, Shen L, Woods SC, Seeley RJ, Zheng S, Jackman A, Tso P. Intestinal satiety protein apolipoprotein AIV is synthe-sized and regulated in rat hypothalamus. Am J Physiol 2001; 280: R1382–R1387.

217. Fujimoto K, Fukagawa K, Sakata T, Tso P. Suppression of food intake by apolioprotein A-IV is mediated through the central nervous system in rats. J Clin Invest 1993; 91: 1830-3. January 2005 Gastrointestinal Hormones and Food Intake 189.

218. Fujimoto K, Machidori H, Iwakiri R, Yamamoto K, Fujisaki J, Sakata T, Tso P. Effect of intravenous administration of apolipoprotein A-IV on patterns of feeding, drinking and ambulatory activity in rats. Brain Res 1993; 608: 233-7.

219. Liu M, Shen L, Doi T, Woods SC, Seeley RJ, Tso P. Neuropeptide Y and lipid increase apolipoprotein AIV gene expression in rat hypothalamus. Brain Res 2003; 971: 232-8.

220. Okada S, York DA, Bray GA, Erlanson-Albertsson C. Enterostatin (Val-Pro-Asp-Pro-Arg), the activation peptide of procolipase, selectively reduces fat intake. Physiol Behav 1991; 49: 1185-9.

221. Shargill NS, Tsuji S, Bray GA, Erlanson-Albertsson C. Enterostatin suppresses food intake following injection into the third ventricle of rats. Brain Res 1991; 544: 137-40.

222. Mei J, Erlanson-Albertsson C. Effect of enterostatin given intravenously and intracerebroventricularly on high-fat feeding in rats. Regul Pept 1992; 41: 209-18.

223. Okada S, York DA, Bray GA, Mei J, Erlanson-Albertsson C. Differential inhibition of fat intake in two strains of rat by the peptide enterostatin. Am J Physiol 1992; 262: R1111-R1116.

224. 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; 50:1714-19.

225. Wren AM, Small CJ, Abbott CR, Dhillo WS, Seal LJ, Cohen MA, et al. Ghrelin causes hyperphagia and obesity in rats. Diabetes 2001; 50: 2540-7.

226. Asakawa A, Inui A, Kaga T, Yuzuriha H, Nagata T, Ueno N, Makino S, Fujimiya M, Niijima A, Fujino MA, Kasuga M. Ghrelin is an appetite-stimulatory signal from stomach with structural resemblance to motilin. Gastroenterol 2001; 120: 337-45.

227. Cummings DE, Clement K, Purnell JQ, Vaisse C, Foster KE, Frayo RS, Schwartz MW, Basdevant A, Weigle DS. Elevated plasma ghrelin levels in Prader Willi syndrome. Nat Med 2002; 8: 643-4.

228. Adolph EF. Urges to eat and drink in rats. Am J Physiol 1947; 151: 110-25.

229. Janowitz HD, Grossman MI. Effect of variations in nutritive density of food in dogs and rats. Am J Physiol 1949; 158: 184-93.

230. Woods SC. The eating paradox: how we tolerate food. Psychol Rev 1991; 98: 488-505.

231. Woods SC, Strubbe JH. The psychobiology of meals. Psychol Bull Rev 1994; 1: 141-155.

232. Campfield LA, Smith FJ, Guisez Y, Devos R, Burn P. Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. Science 1995; 269: 546-9.

233. Seeley RJ, Van Dijk G, Campfield LA, Smith FJ, Nelligan JA, Bell SM, Baskin DG, Woods SC, Schwartz MW. The effect of intraventricular administration of leptin on food intake and body weight in the rat. Horm Metab Res 1996; 28: 664-8.

234. Woods SC, Seeley RJ. Insulin as an adiposity signal. Int J Obes Relat Metab Disord 2001; 25: S35-S38.

235. Banks WA. Is obesity a disease of the blood-brain barrier? Physiological, pathological, and evolutionary considerations. Curr Pharm Des 2003; 9: 801-9.

236. Woods SC, Seeley RJ, Baskin DG, Schwartz MW. Insulin and the blood-brain barrier. Curr Pharm Des 2003; 9: 795-800.

237. Seeley RJ, Moran TH. Principles for interpreting interactions among the multiple systems that influence food intake. Am J Physiol Regul Integr Comp Physiol 2002; 283: R46-R53.

238. Kopin AS, Mathes WF, McBride EW, Nguyen M, Al-Haider W, Schmitz F, Bonner-Weir S, Kanarek R, Beinborn M. The cholecystokinin-A receptor mediates inhibition of food intake yet it is not essential for the maintenance of body weight. J Clin Invest 1999; 103: 383-91.

239. Drucker DJ. Glucagon-like peptides. Diabetes 1998; 47: 159-69.

240. Drucker DJ, Boushey RP, Wang F, Hill ME, Brubaker PL, Yusta B. Biologic properties and therapeutic potential of glucagon-like peptide-2. J Parenter Enteral Nutr 1999; 23: S98-S100.

241. Scrocchi LA, Brown TJ, MacLusky N, Brubaker PL, Auerbach AB, Joyner AL, Drucker DJ. Glucose intolerance but normal satiety in mice with a null mutation in the glucagon-like peptide 1 receptor gene. Nat Med 1996; 2: 1254-8.

242. Sun Y, Ahmed S, Smith RG. Deletion of ghrelin impairs neither growth nor appetite. Mol Cell Biol 2003; 23: 7973-81.

243. Woods SC, West DB, Stein LJ, McKay LD, Lotter EC, Porte SG, Kenney NJ, Porte D Jr. Peptides and the control of meal size. Diabetología 1981; 20: 305-13.

244. Vahl TP, D’Alessio DA. Gut peptides in the treatment of diabetes mellitus. Expert Opin Investig Drugs 2004; 13: 177-88.

245. Miyawaki K, Yamada Y, Ban N, Ihara Y, Tsukiyama K, Zhou H, et al. Inhibition of gastric inhibitory polypeptide signaling prevents obesity. Nat Med 2002; 8: 738-42.

246. Mason EE, Ito C. Gastric bypass in obesity. Surg Clin North Am 1967; 47: 1345-51.

247. Kremen AJ, Linner JH, Nelson CH. An experimental evaluation of the nutritional importance of proximal and distal small intestine. Ann Surg 1954; 140: 439-48.

248. Naslund E, Hellstrom PM, Kral JG. The gut and food intake: an update for surgeons. J Gastrointest Surg 2001; 5: 556-67.

249. Naslund E, Gryback P, Hellstrom PM, Jacobsson H, Holst JJ, Theodorsson E, Backman L. Gastrointestinal hormones and gastric emptying 20 years after jejunoileal bypass for massive obesity. Int J Obes Relat Metab Disord 1997; 21: 387-92.

250. Kellum JM, Kuemmerle JF, O’ Dorisio TM, Rayford P, Martin D, Engle K, Wolf L, Sugerman HJ. Gastrointestinal hormone responses to meals before and after gastric bypass and vertical-banded gastroplasty. Ann Surg 1990; 211: 763-71.

251. Wilson P, Welch NT, Hinder RA, Anselmino M, Herrington MK, DeMeester TR, Adrian TE. Abnormal plasma gut hormones in pathologic duodenogastric reflux and their response to surgery. Am J Surg 1993; 165: 169-77.

252. Adami GF, Cordera R, Camerini G, Marinari GM, Scopinaro N. Recovery of insulin sensitivity in obese patients at short term after biliopancreatic diversion. J Surg Res 2003; 113: 217-21.

253. Greenway SE, Greenway FL III, Klein S. Effects of obesity surgery on non-insulin-dependent diabetes mellitus. Arch Surg 2002; 137: 1109-17.

254. Rubino F, Gagner M. Potential of surgery for curing type 2 diabetes mellitus. Ann Surg 2002; 236: 554-9.

255. Koopmans HS, Sclafani A. Control of body weight by lower gut signals. Int J Obes 1981; 5: 491-5.

256. Koopmans HS, Ferri GL, Sarson DL, Polak JM, Bloom SR. The effects of ileal transposition and jejunoileal bypass on food intake and GI hormone levels in rats. Physiol Behav 1984; 33: 601-9.

257. Boozer CN, Choban PS, Atkinson RL. Ileal transposition surgery attenuates the increased efficiency of weight gain on a high-fat diet. Int J Obes 1990; 14: 869-78.

258. Chen DC, Stern JS, Atkinson RL. Effects of ileal transposition on food intake, dietary preference, and weight gain in Zucker obese rats. Am J Physiol 1990; 258: R269-R273.

259. Strader ADVT, Jandacek RJ, Woods SC, D’Alessio DA, Seeley RJ. Weight loss through ileal transposition is accompanied by increased ileal hormone secretion and synthesis in the rat. Am J Physiol (in press).

260. Tschöp M, Weyer C, Tataranni PA, Devanarayan V, Ravussin E, Heiman ML. Circulating ghrelin levels are decreased in human obesity. Diabetes 2001; 50: 707-9.

261. Williams DL, Cummings DE, Grill HJ, Kaplan JM. Meal-related ghrelin suppression requires postgastric feedback. Endocrinology 2003; 144: 2765-7.

262. Overduin JFR, Cummings DE. Role of the duodenum and macronutrient type in prandial suppression of ghrelin. NAASO Annual Meeting Obesity Research Supplement 2003; 11: A21.

263. 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: 1623-30.

264. Faraj M, Havel PJ, Phelis S, Blank D, Sniderman AD, Cianflone K. Plasma acylation-stimulating protein, adiponectin, leptin, and ghrelin before and after weight loss induced by gastric bypass surgery in morbidly obese subjects. J Clin Endocrinol Metab 2003; 88: 1594-602.

265. Leonetti F, Silecchia G, Iacobellis G, Ribaudo MC, Zappaterreno A, Tiberti C, Iannucci CV, Perrotta N, Bacci V, Basso MS, Basso N, Di Mario U. Different plasma ghrelin levels after laparoscopic gastric bypass and adjustable gastric banding in morbid obese subjects. J Clin Endocrinol Metab 2003; 88: 4227-31.

266. Stoeckli R, Chanda R, Langer I, Keller U. Changes of body weight and plasma ghrelin levels after gastric banding and gastric bypass. Obes Res 2004; 12: 346-50.

267. Geloneze B, Tambascia MA, Pilla VF, Geloneze SR, Repetto EM, Pareja JC. Ghrelin: a gut-brain hormone: effect of gastric bypass surgery. Obes Surg 2003; 13: 17-22.

268. Tritos NA, Mun E, Bertkau A, Grayson R, Maratos-Flier E, Goldfine A. Serum ghrelin levels in response to glucose load in obese subjects post-gastric bypass surgery. Obes Res 2003; 11: 919-24.

269. 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: 3177-83.

270. Meryn S, Stein D, Straus EW. Pancreatic polypeptide, pancreatic glucagon and enteroglucagon in morbid obesity and following gastric bypass operation. Int J Obes 1986; 10: 37-42.

271. Clements RH, Gonzalez QH, Long CI, Wittert G, Laws HL. Hormonal changes after Roux-en Y gastric bypass for morbid obesity and the control of type-II diabetes mellitus. Am Surg 2004; 70: 1-5.

272. Álvarez Bartolomé M, Borque M, Martínez-Sarmiento J, Aparicio E, Hernández C, Cabrerizo L, Fernández-Represa JA. Peptide YY recretion in morbidly obese patients before and after vertical banded gastroplasty. Obes Surg 2002; 12: 324-7.

273. Gianetta E, Bloom SR, Sarson DL, Civalleri D, Bonalumi U, Griffanti Bartoli F, Friedman D, Pitton L, Binda PL, Degrandi R, Scopinaro N. Behavior of plasma enteroglucagon and neurotensin in obese patients subjected to biliopancreatic bypass. Boll Soc Ital Biol Sper 1980; 56: 1915-21.

274. Sarson DL, Scopinaro N, Bloom SR. Gut hormone changes after jejunoileal (JIB) or biliopancreatic (BPB) bypass surgery for morbid obesity. Int J Obes 1981; 5: 471-80.

275. Ockander L, Hedenbro JL, Rehfeld JF, Sjolund K. Jejunoileal bypass changes the duodenal cholecystokinin and somatostatin cell density. Obes Surg 2003; 13: 584-90.

276. Havel PJ. Peripheral signals conveying metabolic information to the brain: short-term and long-term regulation of food intake and energy homeostasis. Exp Biol Med (Maywood) 2001; 226: 963-77.