Oxintomodulina e obesidade
Palavras-chave:
Agentes anti-obesidade, Gastrointestinais, Hormônios, Obesidade, Peptídeos, Perda de pesoResumo
Desde o descobrimento da leptina, avanços consideráveis foram obtidos na caracterização dos mecanismos hipotalâmicos do controle da ingestão alimentar e, atualmente, a oxintomodulina é reconhecida como um regulador da homeostase energética. O presente artigo de revisão enfoca algumas das mais relevantes inter-relações do hormônio oxintomodulina com o apetite, a homeostase energética e aspectos de seu papel na bioquímica e fisiologia nutricional. A oxintomodulina é um peptídeo intestinal anorexígeno produzido pelas células L do intestino. Recentes estudos têm demonstrado que em longo prazo a administração de oxintomodulina reduz a ingestão alimentar e o ganho de peso. Pesquisas em humanos têm verificado que o seu uso reduz o consumo energértico em 25%. Portanto, a oxintomodulina representa uma potente terapia anti-obesidade. Entretanto, o mecanismo de ação da oxintomodulina ainda é desconhecido. Atuais evidências sugerem que tem ação via receptor do peptídeo semelhante ao glucagon 1. Além disso, a literatura mostra que, juntamente com a adoção de hábitos saudáveis e a mudança do estilo de vida, a oxintomodulina pode proporcionar menor avanço da obesidade.
Referências
World Health Organization. Global strategy on diet, physical activity and health: obesity and overweight. Geneva. [cited 2007 Mar 4]. Available from:<http://www.who.int/dietphysicalactivity/publications/facts/obesity/en/>.
Instituto Brasileiro de Geografia e Estatística. Pesquisa de orçamento familiar (POF), 2002/2003. Rio de Janeiro. [acesso 2009 fev 2]. Disponível em: <http://www.ibge.gov.br>.
Baynes KCR, Dhillo WS, Bloom SR. Regulation of food intake by gastrointestinal hormones. Curr Opin Gastroenterol. 2006; 22(6):626-31. doi: 10.1097/01.mog.0000245537.43142.63.
Halpern ZSC, Rodrigues MDB, Costa RF. Determinantes fisiológicos do controle de peso e apetite. Rev Psiq Clin. 2004; 31(4):150-3. doi: 10.1590/S0101-60832004000400002.
Wynne K, Stanley S, Bloom S. The gut and regulation of body weight. J Clin Endocrinol Metab. 2004; 89(6):2576-82. doi: 10.1210/jc.2004-0189.
Bataille D, Gespach C, Tatemoto K, Marie JC, Coudry AM, Rosselin G, et al. Bioactive enteroglucagon (oxyntomodulin): present knowledge on its chemical structure and its biological activities. Peptides. 1981; 2(Suppl 2): 41-4.
Cohen MA, Ellis SM, Lê Roux CW, Batterham RL, Park A, Patterson M, et al. Oxyntomudulin suppesses appetite and reduces food intake in humans. J Clin Endocrinol Metab. 2003; 88(10): 4696-701. doi: 10.1210/jc.2003-030421.
Pimentel GD, Mota JF, Guimaraes MP, Fioravante MA. A oxintomodulina como uma nova terapia anti-obesidade [Abstract]. Rev Bras Med. 2007; 64(Supl. 1):131.
White NE, Dhillo WS, Liu YL, Small CJ, Kennett GA, Gardiner JV, et al. Co-administration of SR141716 with peptide YY3-36 or oxyntomodulin has additive effects on food intake in mice. Diabetes Obes Metabol. 2008; 10(2):167-70. doi: 10.1111/j.1463-1326.2007.00807.x.
Druce MR, Minnion JS, Field BC, Patel SR, Cuenco-Shilito J, Tilby M, et al. Investigation of structureactivity relationships of oxyntomodulin using oxyntomodulin analogues. Endocrinology. 2009; 150(4):1712-22. doi: 10.1210/en.2008-0828.
Parkinson JRC, Chaudhri OB, Kuo YT, Field BCT, Herlihy AH, Dhillo WS. Differential patterns of neuronal activation in the brainstem an hypothalamus following peripheral injection of GLP-1, oxyntomodulin and lithium chloride in mice detected by manganese-enhanced magnetic resonance imaging (MEMRI). Neuroimage. 2009; 44(3):1022-31. doi: 10.1016/j.neuroimage.2008.09.047.
Tatemoto K, Mutt V. Isolation of two novel candidate hormones using a chemical method for finding naturally occurring polypeptides. Nature. 1980; 285(5764):417-8. doi: 10.1038/285417a0.
Blache P, Kevran A, Bataille D. Oxyntomodulin and glicentin: brain gut peptides in the rat. Endocrinology. 1988; 123(6):2782-7. doi: 10.1210/endo-123-6-2782.
Wynne K, Park AJ, Small CJ, Patterson M, Ellis SM, Murphy KG, et al. Subcutaneous oxyntomodolin reduces body weight in overweight and obese subjects: a double-blind, randomized, controlled trial. Diabetes. 2005; 54(8):2390-5. doi: 10.2337/diabetes.54.8.2390.
Baldissera FG, Holst JJ. Glucagon-related peptides in the human gastrointestinal mucosa. Diabetologia. 1984; 26(3):223-8. doi: 10.1007/BF00252412.
Le Quellec A, Kervran A, Blache P, Ciurana AJ, Bataille D. Oxyntomodulin-like immunoreactivity: diurnal profile of a new potential enterogastrone. J Clin Endocrinol Metab. 1992; 74(6):1405-9.
Holst JJ. Enteroglucagon. Ann Rev Physiol. 1997; 59:257-71. doi: 0066-4278/97/0315-0257$08.00.
Blázquez E, Álvarez E, Albusac JMR, Roncero I, Velázquez E. Papel de los péptidos semejantes al glucagón sobre el control de la ingesta de alimentos. Rev Esp Obes. 2004; 2(2):99-112.
Stepanenko VN, Esipov RS, Gurevich AI, Chupova LA, Miroshnikov AI. Recombinant oxyntomodulin. Rus J Bioorg Chem. 2007; 33(2):227-32. doi: 10.1134/S1068162007020045.
Druce MR, Bloom SR. Oxyntomodulin: a novel potential treatment for obesity. Treat Endocrinol. 2006; 5(5):265-72.
Anini Y, Fu-Cheng X, Cuber JC, Kervran A, Chariot J, Rozé C. Comparasion of the postprandial release of peptide YY and proglucagon-derived peptides in the rat. Pfugers Arch. 1999; 438(3):299-306. doi: 10.1007/s004240050913.
Schjoldager B, Mortensen PE, Myhre J, Christiansen J, Holst JJ. Oxyntomodulin from distal gut: role in regulation of gastric and pancreatic functions. Dig Dis Sci. 1989; 34(9):1411-9.
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(5):471-80.
Wynne K, Bloom SR. The role of oxyntomodulin and peptide tyrosine-tyrosine (PYY) in appetite control. Nature. 2006; 2(11):612-20. doi: 10.1038/ncpendmet0318.
Besterman HS, Cook GC, Sarson DL, Christofides ND, Bryant MG, Gregor M, et al. Gut hormones in tropical malabsorption. Br Med J. 1979; 2(6200): 1252-5.
Holst JJ, Sorensen TI, Andersen AN, Stadil F, Andersen B, Lauritsen KB, et al. Plasma enteroglucagon after jejunoileal bypass with 3:1 or 1:3 jejunoileal ratio. Scand J Gastroenterol. 1979; 14(2):205-7.
Verdich C, Toubro S, Buemann B, Madsen JL, Holst JJ, Astrup A. The role of postprandial releases of insulin and incretin hormones in meal-induced satiety-effect of obesity and weight reduction. Inter J Obes Relat Metab Disord. 2001; 25(8):1206-14.
Guido R, Leiter AB, Kopin AS, Bordi C, Solcia E. The “normal” endocrine cell of the Gut: changing concepts and new evidences. Ann N Y Acad Sci. 2004; 1014(1):1-12. doi: 10.1196 annals.1294.001.
Martins MN, Telles MM, Zemdegs JC, Andrade IS, Ribeiro EB, Miranda A. Evaluation of new leptin fragments on food intake and body weight of normal rats. Regul Pept. 2008; 153(1-3):77-82. doi: 10.1016/j.regpep.2008.11.013.
Sainsbury A, Cooney GJ, Herzog H. Hypothalamic regulation of energy homeostasis. Best Pract Res Clin Endocrinol Metab. 2002; 16(4):623-37. doi: 10.1053/beem.2002.0230.
Chaudhri OB, Parkinson JRC, Herlihy AH, Salem V, Kuo YT, Bell JD, et al. Manganese-enchanced MRI demonstrates that oxyntomodulin and GLP-1 affect neuronal activity in distinct regions of the brain. Endocrine Abstracts. 2007; 13:OC27.
Baldissera FG, Holst JJ, Knuhtsen S, Hilsted L, Nielsen OV. Oxyntomodulin (glicentin-(33-69)): pharmacokinetics, binding to liver cell membranes, effects on isolated perfused pig pancreas, and secretion from isolated perfused lower small intestine of pigs. Regul Pept. 1988; 21(1-2):151-66. doi: 10.1016/0167-0115(88)90099-7.
Sowden GL, Drucker DJ, Weinshenker D, Swoap SJ. Oxyntomodulin increases intrinsic heart rate in mice independent of the glucagon-like peptide-1 receptor. Am J Physiol Regul Integr Comp Physiol. 2007; 292(2):R962-R70. doi: 10.1152/ajpregu.00405.2006.
Fehmann HC, Jiang J, Schweinfurth J, Wheeler MB, Boyd AE, Goke B. Stable expression of the rat GLP-I receptor in CHO cells: activation and binding characteristics utilizing GLP-I (7-36)-amide, oxyntomodulin, exendin-4, and exendin (9-39). Peptides. 1994; 15(3):453-6.
Chaudhri OB, Parkinson JRC, Kuo YT, Druce MR, Herlihy AH, Bell JD, et al. Differential hypothalamic neuronal activation following peripheral injection of GLP-1 and oxyntomodulin in mice detected by manganese-enhanced magnetic resonance imaging. Biochem Biophys Res Commun. 2006; 350(2):298-306. doi:10.1016/j.bbrc.2006.09.033.
Schepp W, Dehne K, Riedel T, Schmidtler J, Schaffer K, Classen M. Oxyntomodulin: a cAMP-dependent stimulus of rat parietal cell function via the receptor for glucagon-like peptide 1 (7-36) NH2. Digestion. 1996; 57(6):398-405. doi: 10.1159/000201367.
Baggio LL, Huang Q, Brown TJ, Drucker DJ. Oxyntomodulin and glucagon-like peptide-1 differentially regulate murine food intake and energy expenditure. Gastroenterology. 2004; 127(2):54658.doi:10.1053/j.gastro.2004.04.063.
Murphy KG, Bloom SR. Gut hormones and the regulation of energy homeostasis. Nature. 2006; 444(7121):854-9. doi: 10.1038/nature05484.
Druce M, Ghatei M. Oxyntomodulin. Curr Opin Endrocrinol Diabetes. 2006; 13(1):49-55.
Parlevliet ED, Heijboer AC, Schröder-van der Elst JP, Havekes LM, Romijn JÁ, Pijl H, et al. Oxyntomodulin ameliorates glucose intolerance in mice fed a high- -fat diet. Am J Physiol Endocrinol Metab. 2008; 294(1):E142-7. doi: 10.1152/ajpendo.00576.2007.
Dakin CL, Gunn I, Small CJ, Edwards CM, Hay DL, Smith DM, et al. Oxyntomodulin inhibits food intake in the rat. Endocrinology. 2001; 142(10): 4244-50.
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(6):E1173-77. doi: 10.1152/ajpendo.00233.2002.
Dakin CL, Small CJ, Batterham RL, Neary NM, Cohen MA, Patterson M, et al. Peripheral oxyntomodulin reduces food intake and body weight gain in rats. Endocrinology. 2004; 145(6):2687-95. doi: 10.1210/en.2003-1338.
Maida A, Lovshin JA, Baggio LL, Drucker DJ. The glucagon-like peptide-1 receptor agonist oxyntomodulin enhances β-cell function but does not inhibit gastric emptying in mice. Endocrinology. 2008; 149(11):5670-8. doi: 10.1210/en.2008-0336.
Cline MA, Bowden CN, Nandar W, Rogers JO. Central oxyntomodulin causes anorexigenic effects associated with the hypothalamus and alimentary canal in chicks (Gallus gallus). Comp Biochem Physiol A Mol Integr Physiol. 2008; 149(4):405-10. doi: 10.1016/j.cbpa.2008.01.038.
Nassar MF, Gomaa SM, El-Batrawy SR. Low ghrelin level affects biomarkers in childhood obesity. Nutr Res. 2007; 27(10):605-11. doi: 10.1016/j.nutres.2007.06.014.
Dâmaso AR, Tock L, Tufik S, Prado WL, Stella SG, Fisberg M, et al. Tratamiento multidisciplinar reduce el tejido adiposo visceral, leptina, grelina y la prevalencia de esteatosis hepática no alcohólica (NAFLD) en adolescentes obesos. Rev Bras Med Esp. 2006; 12(5):263-7. doi: 10.1590/S1517-86922006000500008.
Pellissier S, Sasaki K, Le-Nguyen D, Bataille D, Jarrousse C. Oxyntomodulin and glicentin are potent inhibitors of the fed motility pattern in small intestine. Neurogastroenterol Motil. 2004; 16(4):455-63. doi: 10.1111/j.1365-2982.2004.00528.x.
Wynne K, Park AJ, Small CJ, Meeran K, Ghatei MA, Frost GS, et al. Oxyntomodulin increases energy expenditure in addition to decresing energy intake in overweight and obese humans a randomised controlled trial. Int J Obes. 2006; 30(12):1729-36. doi: 10.1038/sj.ijo.0803344.
Lê Roux CW, Aylwin SJ, Batterham RL, Borg CM, Coyle F, Prasad V, et al. Gut hormone profiles following bariatric surgery favor an anorectic state, facilitate weight loss, and improve metabolic parameters. Ann Surg. 2006; 243(1):108-14. doi: 10.1097/01.sla.0000183349.16877.84.
Hanada T, Toshinai K, Date Y, Kajimura N, Tsukada T, Hayashi Y, et al. Upregulation of ghrelin expression in cachectic nude micebearing human melanoma cells. Metabolism. 2004; 53(1):84-8. doi: 10.1016/j.metabol.2003.06.004.
Lindeman J, Pijl H, van Dielen F, Lentjes E, van Leuven C, Kooistra T. Ghrelin and the hyposomatotropism of obesity. Obes Res. 2002; 10(11):1161-6. doi: 10.1038/oby.2002.157
Tschöp M, Weyer C, Tataranni PA, Devanarayan V, Ravussin E, Heiman ML. Circulating ghrelin levels are decreased in human obesity. Diabetes. 2001; 50(4):707-9. doi: 10.2337/diabetes.50.4.707.
Murphy KG, Bloom SR. Gut hormones in the control of appetite. Exp Physiol. 2004; 89(5): 507-16. doi: 10.1113/expphysiol.2004.027789.
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