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Asociación Mexicana de Gastroenterología

2005, Number 4

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Rev Gastroenterol Mex 2005; 70 (4)

Ghrelin: beyond hunger regulation

Milke GMP

Language: Spanish
References: 75
Page: 465-473
PDF size: 64.36 Kb.


ABSTRACT

Man ingests food to mitigate hunger (mediated by physiological and biochemical signals), satisfy appetite (subjective sensation) and because of psychosocial reasons. Satiation biomarkers (stop feeding) are gastric distention and hormones (CCK, GLP-1) and satiety biomarkers (induce feeding) are food-induced thermogenesis, body temperature, glycaemia and also hormones (insulin, leptin and ghrelin). Oxidative metabolism/body composition, tryptophan/serotonin and proinflammatory cytokines are also implicated on hunger physiology. At the present time, ghrelin is the only known circulating orexigenic with potential on hunger/body weight regulation. It is a neuropeptide (endogenous ligand for the GH secretagogue) recently isolated from the oxyntic mucosa and synthesized mainly in the stomach. Its blood concentration depends on diet, hyperglucemia and adiposity/leptin. It is secreted 1-2 hours preprandially and its concentration decreases drastically during the postprandium. Ghrelin acts on the lateral hypothalamus and theoretically inhibits proinflammatory cytokine secretion and antagonizes leptin. Ghrelin physiologically increases food intake and stimulates adipogenesis, gastrointestinal motility and gastric acid secretion, and has other hormonal and cardiovascular functions. Ghrelin blood concentration is reduced in massive obesity, non-alcoholic steatohepatitis, polycystic ovary syndrome, acromegaly, hypogonadism, ageing, short bowel syndrome and rheumatoid arthritis; and increased in primary or secondary anorexia, starvation, chronic liver disease and celiac disease. Cerebral and peritoneal ghrelin administration (rats) and systemic administration (rats and healthy volunteers, cancer patients or patients on peritoneal dialysis) promotes food consumption and increases adiposity, of utmost importance in the treatment of patients with anorexia


REFERENCES

  1. Meiselman HL. The contextual basis for food acceptance. In: Meiselman HL, Mac Fie HJ (eds.). Food choice, acceptance and consumption. Londres: Blackie Academic & Professional; 1996, p. 239-63.

  2. Graaf C, Blom AM, Smeets PAM, Staufelu A, Hendriks HFJ. Am J Clin Nutr 2004; 79: 946-61.

  3. le Roux CW, Ghatei MA, Gibbs JSR, Bloom SR. The putative satiety hormone PYY is raised in cardiac cachexia associated with primary pulmonary hypertension. Heart 2005; 91: 241-2.

  4. 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.

  5. Mc Minn JE, Sinderlar DK, Havel PJ, Schawrtz MW. Leptin deficiency induced by fasting impairs the satiety response to cholecystokinin. Endocrinology 2000; 141: 4442-8.

  6. Wang L, Barachina MD, Martínez V, Wei JY, Tache Y. Synergistic interaction between CCK and leptin to regulate food intake. Regul Pept 2000; 92: 79-85.

  7. 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.

  8. Muurahainen 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: 645-9.

  9. Gutzwiller J, Drewe J, Ketterer S, Hildebrand P, Krautheim A, Beglinger C. Interaction between CCK and a preload on reduction of food intake is mediated by CCK-A receptors in humans. Am J Physiol Regul Integr Comp Physiol 2000; 279: R139-95.

  10. Lieverse RJ, Jansen JB, Masclee AM, Lamers CB. Effects of somatostatin on human satiety. Neuroendocrinology 1995; 61: 112-16.

  11. Westerterp-Plantenga MS, Marken Lichtenbelt WD, Strobbe H, Schrauwen P. Energy metabolism in humans at a lowered ambient temperature. Eur J Clin Nutr 2002; 56: 288-96.

  12. Westerterp-Plantenga MS, Wouters L, ten Hoor F. Deceleration in cumulative food intake curves, changes in body temperature and diet-induced thermogenesis. Physiol Behav 1990; 48: 831-6.

  13. Mayer J. Regulation of the energy intake and the body weight. The glucostatic theory and the lipostatic hypothesis. Ann NY Acad Sci 1955; 63: 15-42.

  14. Rodin J, Wack J, Ferrannini E, De Fronzo Ra. Effect of insulin and glucose on feeding behavior. Metabolism 1985; 34: 826-31.

  15. Verdich C, Toubro S, Buemann B, Lysgard MJ, Juul HJ, Astrup A. The role of postprandial releases of insulin and incretin hormones in meal-induced satiety – effect of obesity and weight reduction. Int J Obes Relat Metab Disord 2001; 25: 1206-14.

  16. Chapelot D, Aubert R, Marmonier C, Chabert M, Louis-Sylvestre J. An endocrine and metabolic definition of the intermeal interval in humans: evidence for a role of leptin on the prandial pattern through fatty acid disposal. Am J Clin Nutr 2000; 72: 421-31.

  17. Verdich C, Ellliott R, Morgan L, Tredger J, Deacon S, Wright J, Marks V. Glucagon-like-peptide-1 (7-36) amide and glucose-dependent insulinotropic polypeptide secretion in response to nutrient ingestion in man: acute postprandial and 24-h secretion patterns. J Endocrinol 1993; 138: 159-66.

  18. Levine AS, Kotz CM, Gosnell BA. Sugars and fats: the neurobiology of preference. J Nutr 2003; 133: 831S-834S.

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

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

  21. Pollak CP, Green J, Smith GP. Blood glucose prior to meal request in humans isolated from all temporal cues. Physiol Behav 1989; 46: 529-34.

  22. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-reseasing acylated peptide from stomach. Nature 1999; 402: 656-60.

  23. Date Y, Kojima M, Hosoda H, et al. Ghrelin, a novel growth hormone-releasing acylated peptide, is synthesided in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans. Endocrinology 2000; 141: 4255-61.

  24. Gnanapavan S, Kola B, Bustin SA, Morris DG, Mc Gee P, Fairclough P, Bhattacharya S, Carpenter R, Grossman AB, Korbonits M. The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. J Clin Endocrinol Metab 2002; 87; 2988.

  25. Choi K, Roh SG, Hong YH, Shrestha YB, Hishikawa D, Chen C, Kojima M, Kangawa K, Sasaki S. The role of ghrelin and growth hormone secretatogues receptor on rat adipogenesis. Endocrinology 2003; 144: 754-9.

  26. Baldanzi G, Filigheddu N, Cutrupi S, Catapano F, Bonissoni S, Fubini A, Malan D, Baj G, Granata R, Broglio F. Grhelin and des-acyl ghrelin inhibit cell death in cardiomyocytes and endothelial cells through ERK1/2 and PI 3-kinase/AKT. J Cell Biol 2002; 159: 1029-37.

  27. Korbonits M, Goldstone AP, Gueorguiev M, Grossman AB. Ghrelin-a hormone with multiple functions. Frontiers Neuroendoricnology 2004; 25: 27-68.

  28. Ariyasu H, Takaya K, Tagami T, Ogawa Y, Hosoda K, Akamizu T, Suda M, Koh T, Natsui K, Toyooka S, Shirakami G, Usui T, Shimatsu A, Doi K, Hosoda H, Kojima M, Kangawa K, Nakao K. Stomach is a major source of circulating ghrelin and feeding state determines plasma ghrelin-like immunoreactivity levels in humans. J Clin Endocrinol Metab 2001; 86: 4753-8.

  29. Krsek M, Rosická M, Papezová H, Krízova J, Kotrlikova E, Haluzk M, Justova V, Lacinova Z, Jarkovska Z. Plasma ghrelin levels in patients with short bowel syndrome. Endocr Res 2002; 28: 27-33.

  30. Wren AM, Small CJ, Abbott CR, Dhillo WS, Seal LJ, Cohen MA, Batterham RL, Taheri S, Stanley SA, Ghatei MA, Bloom SR. Ghrelin causes hyperphagia and obesity in rats. Diabetes 2001; 50: 2540-47.

  31. Masuda Y, Tanaka T, Inomata N, Ohnuma N, Tanaka S, Itoh Z, Hosoda H, Kojima M, Kangawa K. Ghrelin stimulates gastric acid secretion and motility in rats. Biochem Biophys Res Commun 2000; 276: 905-8.

  32. 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.

  33. Cummings DE, Frayo RS, Marmonier C, Chapelot D. Plasma ghrelin levels and hunger scores in humans initiating meals voluntarily withoug time-and food-related cues. Am J Physiol Endocrinol Metab 2004; 287; E 297-304.

  34. Schaller G, Schmidt A, Pleiner J, Woloszczuk W, Wolzt M, Luger A. Plasma ghrelin concentrations are not regulated by glucose or insulin: a double-blind, placebo-controlled cross-over clamp study. Diabetes 2003; 52: 15-20.

  35. Beck B, Musse N, Stricker-Krongrad A. Ghrelin, macronutrient intake and dietary preferences in long-evans rats. Biochem Biophys Res Commun 2002; 292: 1031-5.

  36. Lee HM, Wang G, Englander EW, Kojima M, Greeley GH Jr. Ghrelin, a new gastrointestinal endocrine peptide that stimulates insulin secretion: enteric distribution, ontogeny, influence of endocrine and dietary manipulations. Endocrinology 2002; 143; 185-90.

  37. Otero M, Nogueiras R, Lago F, Diéguez C, Gómez-Reino JJ, Gualillo O. Chronic inflammation modulates ghrelin levels in humans and rats. Rheumatology 2003; 43; 306-10.

  38. Tacke F, Brabant G, Kruck E, Horn R, Schöffski P, Hecker H, Manns MP, Trautwein C. Ghrelin in chronic liver disease. J Hepatol 2003; 38: 447-54.

  39. Dixit VD, Schaffer EM, Pyle RS, et al. Ghrelin inhibits leptin-and activation-induced proinflammatory cytokine expression by human monocytes and T cells. J Clin Invest 2004; 114: 57-66.

  40. García JM, García-Touza M, Hijazi RA, Taffet G, Epner D, Mann D, Smith RG, Cunningham GR, Marcelli M. Active ghrelin levels and active/total ghrelin ratio in cancer-induced cachexia. J Clin Endocrinol Metab 2005; 90: 2920-6.

  41. Akasawa A, Inui A, Kaga T, Yuzuriha H, Nagata T, Ueno N. Makino S, Fujimiya M, Nijijama A, Fijino MA, Kasuga M. Ghrelin is an appetite-stimulatory signal from stomach with structural resemblance to motilin. Gastroenterology 2001; 120; 337-45.

  42. Lawrence CB, Snape AC, Baudoin FM, Luckman SM. Acute central ghrelin and GH secretagogues induce feeding and activate brain appetite centres. Endocrinology 2002; 143: 155-62.

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

  44. Thompson NM, Gill DA, Davies R, Loveridge N, Houston PA, Robinson IC, Wells T. Ghrelin and des-octanoyl ghrelin promote adipogenesis directly in vivo by a mechanism independent of the type 1a growth hormone secretagogue receptor. Endocrinology 2004; 145: 234-42.

  45. Muccioli G, Pons N, Ghe C, Catapano F, Granata R, Ghigo E. Ghrelin and des-acyl ghrelin both inhibit isoproterenol-induced lipolysis in rat adipocytes via a non-type 1a growth hormone secretagogue receptor. Eur J Pharmacol 2004; 498: 27-35.

  46. van de Lely AJ, Tschop M, Heiman ML, Ghigo E. Biological, physiological, pathophysiological and pharmacological aspects of ghrelin. Endocr Rev 2004; 25: 426-57.

  47. Nagaya N, Miyatake K, Uematsu M, Oya H, Shimizu W, Hosoda H, Kojima M, Nakanishi N, Mori H, Kangawa K. Hemodynamic, renal, and hormonal effects of ghrelin infusion in patients with chronic heart failure. J Clin Endocrinol Metab 2001; 86: 5854-9.

  48. Tena-Sempere M. Ghrelin: novel regulator of gonadal function. J Endocrinol Invest 2005; 28(5 Suppl.): 26-9.

  49. Hubina E, Goth M, Korbonits M. Ghrelin-a hormone with multiple functions. Orv Hetil 2005; 146(25): 1345-51.

  50. Murray CD, Martin NM, Patterson M, Taylor S, Ghatei MA, Kamm MA, Johnston C, Bloom SR, Emmanuel AV. Ghrelin enhances gastric emptying in diabetic gastroparesis: a double-blind, placebo-controlled, cross-over study. Gut 2005; 5 (en prensa).

  51. Edholm T, Levin F, Hellstrom PM, Schmidt PT. Ghrelin stimulates motility in the small intestine of rats through intrinsic cholinergic neurons. Regul Pept 2004; 121: 25-30.

  52. Nagaya N, Kangawa K. Ghrelin, a novel growth hormone-releasing peptide, in the treatment of chronic heart failure. Regul Pept 2003; 114: 71-7.

  53. Murata M, Iokimura Y, Iida K, Matsumoto M, Sowa H, Kaji H, et al. Ghrelin modulates the downstream of insulin signaling in hepatoma cells. J Biol Chem 2002; 277: 5667-74.

  54. Ghe C, Cassom P, Catapan F, Marrocco T, Deghenghi R, Ghigo E, Muccioli G, Papotti M. The antiproliferative effect of synthetic peptidyl GH secretagogues in human CALU-1 lung carcinoma cells. Endocrinology 2002; 43: 484-91.

  55. Marzullo P, Verti B, Savia G,Walker GE, Guzzaloni G, Tagliaferri M, di Blasio A, Liuzzi A. The relationship between active ghrelin levels and human obesity involves alerations in resting energy expenditure. J Clin Endocrinol Metab 2004; 89: 936-9.

  56. Marchesini G, Pagotto U, Bigianesi E, de Lasio R, Manini R, Van E, Pasquali R, Mlechionda N, Rizzeto M. Low ghrelin concentrations in nonalcoholic fatty liver diseases are related to insulin resistance. J Clin Endocrinol Metab 2003; 88: 5674-9.

  57. Rigamonti AE, Pincelli AI, Corrá B, Viarengo R, Bonomo SM, Galimberti D, Scacchi, Scarpini E, Cavagnini F, Müller EE. Plasma ghrelin concentrations in elderly subjects: comparison with anorexic and obese patients. J Endocrinol 202; 175: R1-R5.

  58. Nagaya N, Uematsu M, Kojima M, Date Y, Nakazato M, Okumura H, Hosoda H, Shimizu W, Yamagishi M, Oya H, Koh H, Yutani C, Kangawa K. Elevated circulating level of ghrelin in cachexia associated with chronic heart failure: relationships between ghrelin and anabolic/catabolic factors. Circulation 2001; 104; 2034-8.

  59. Shimizu Y, Nagaya N, Isobe T, Imazu M, Okumura H, Hosoda H, Kojima M, Kangawa K, Kohno N. Increased plasma ghrelin level in lung cancer cachexia. Clin Cancer Res 2003; 9: 774-8.

  60. Hanada T, Toshinai K, Date Y, Kajimura N, Tsukada T, Hayashi Y, Kangawa K, Nakazato M. Upregulation of ghrelin expression in cachectic nude mice bearing human melanoma cells. Metabolism 2004; 53: 84-88.

  61. 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 201; 86: 5992-5.

  62. Peracchi M, Conte D, Terrani C, Pizzinelli S, Gebbia C, Cappiello V, Spada A, Bardella MT. Circulating ghrelin levels in celiac patients. Am J Gastroenterol 2003; 98: 2474-8.

  63. Hanada T, Toshinai K, Kajimura N, Nara-Ashizawa N, Tsukada T, Hayashi Y, Osuye K, Kangawa K Matsukura S, Nakazato M. Anti-cachectic effect of ghrelin in nude mice bearing human melanoma cells. Biochem Biophys Res Commun 2003; 301: 275-9.

  64. Marchesini G, Bianchi G, Lucidi P, Villanova N, Solí M, de Feo P. Plasma ghrelin concentrations, food intake, and anorexia in liver failure. J Clin Endocrinol Metab 2004; 89: 2136-41.

  65. Aguilera A, Cirugeda A, Amair R, Sansone G, Alegre L, Codoceo R, Bajo A, del Peso G, Diez JJ, Sánchez-Tomero JA, Selgas R. Ghrelin plasma levels and appetite in peritoneal dialysis patients. Adv Perit Dial 2004; 20: 194-9.

  66. Wren AM, Small CJ, Ward HL, Murphy KG, Dakin CL, Taheri S, Kennedy AR, Roberts GH, Morgan DG, Ghatei MA, Bloom SR. The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion. Endocrinology 2000; 141: 4325-8.

  67. le Roux CW, Neary NM, Halsey TJ, Small CJ, Martínez-Isla AM, Ghatei MA, Theodorou NA, Bloom SR. Ghrelin does not stimulate food intake in patients with surgical procedures involving vagotomy. J Clin Endocrinol Metab 2005; 90: 4521-4.

  68. 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: 2832-6.

  69. Wynne K, giannitsopoulou K, Small CJ, Patterson M, Frost G, Ghatei MA, Brown EA, Bloom SR, Choi P. Subcutaneous ghrelin enhances acute food intake in malnourished patients who receive maintenance dialysis: a randomised, placebo-controlled trial. J Am Soc Nephrol 2005; 16: 2111-18.

  70. Peeters TL. Central and peripheral mechanisms by which ghrelin regulates gut motility. J Physiol Pharmacol 2003; (54 Suppl.)4: 95-103.

  71. Enomoto M, Nagaya N, Uematsu , Okumura H, Nakagawa E, Ono F, Hosoda H, Oya H, Kojima M, Kanmatsuse K, Kangawa K. Cardiovascular and hormonal effects of subcutaneous administration of ghrelin, a novel growth hormone- releasing peptide, in healthy humans. Cln Sci (London) 2003; 105: 431-5.

  72. Akamizu T, Takaya K, Irako T, Hosoda H, Teramukai S, Matsuyama A, Tada H, Miura K, Shimizu A, Fukushima M, Yokode M, Tanaka K, Kangawa K. Eur J Endocrinol 2004; 150: 447-55.

  73. Druce MR; Wren AM; Park AJ, Milton JE, Patterson M, Frost G, Ghatei MA, Small C, Bloom SR. Ghrelin increases food intake in obese as well as lean subjects. Int J Obes Relat Metab Disord 2005; 29: 1130-6.

  74. Wang G, Lee HM, Englander E, Greeley GH Jr. Ghrelin-not just another stomach hormone. Regul Pept 2002; 105: 75-81.

  75. Murray CD, Kamm MA, Bloom SR, Emmanuel AV. Ghrelin for the gastroenterologist: history and potential. Gastroenterology 2003; 125: 1492-502.




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