Gaceta Médica de México

Contenido por año, Vol. y Num.

Índice de este artículo

Información General

Instrucciones para Autores

Mensajes al Editor


>Revistas >Gaceta Médica de México >Año 2008, No. 6

Almanza-Pérez JC, Blancas-Flores G, García-Macedo R, Alarcón-Aguilar FJ, Cruza M
Leptina y su relación con la obesidad y la diabetes mellitus tipo 2. J
Gac Med Mex 2008; 144 (6)

Idioma: Español
Referencias bibliográficas: 79
Paginas: 535-542
Archivo PDF: 118.92 Kb.

[Texto completo - PDF]


En los últimos años, el número de pacientes con alteraciones metabólicas,tales como obesidad, diabetes mellitus tipo 2, hipertensión, etcétera, se ha incrementado. El aumento en el peso corporal, resultante de los factores genéticos, ambientales y nutricionales, tiene un papel muy importante en el desarrollo de diversas alteraciones metabólicas. En 1994 se describió al gen de la obesidad (ob) que codifica para la proteína leptina, molécula importante en la regulación del peso corporal. La ganancia en el peso normalmente correlaciona con un incremento de la proteína leptina, generándose a largo plazo un estado de resistencia a la misma. Además de esta relación con la obesidad, la leptina también se ha asociado con la diabetes mellitus tipo 2 y con la resistencia a la insulina, característica principal de esta patología. La leptina también se ha relacionado con otras enfermedades tales como cáncer, trastornos psicológicos y sexuales, entre otros. En este trabajo se analizan algunos aspectos bioquímicos y molecu lares relacionados con la fisiología de la leptina; se hace énfasis en las consecuencias patológicas que causan su desregulación en la obesidad y la diabetes mellitus tipo 2.

Palabras clave: Leptina, gen ob, adipocinas, tejido adiposo, obesidad, diabetes.


  1. Kennedy GC. The role of depot fat in the hypothalamic control of food intake in the rat. Proc R Soc London Ser B 1953;140:578-596.

  2. Bays H, Mandarino L, DeFronzo RA. Role of the adipocyte, free fatty acids, and ectopic fat in pathogenesis of type 2 diabetes mellitus: peroxisomal proliferator-activated receptor agonists provide rational therapeutic approach. J Clin Endocrinol Metab 2004;89:463-478.

  3. Lin Y, Berg A, Iyengar P, Lam T, Giacca A, Combs T, et al. The hyperglycemia- induced inflammatory response in adipocytes: The role of reactive oxygen species. J Biol Chem 2005;280:4617-4625.

  4. Bloomgarden ZT. The Endocrine Society Meeting: topics in insulin sensitivity and hypertension. Diabetes Care 2003;26:2668-2679.

  5. Sánchez-Muñoz F, García-Macedo R, Alarcón-Aguilar F, Cruz M. Adipocitocinas, tejido adiposo y su relación con células del sistema inmune. Gac Med Mex 2005;141:505-512.

  6. Rajala MW, Scherer PE. Minireview. The adipocyte: at the crossroads of energy homeostasis, inflammation, and atherosclerosis. Endocrinology 2003;144:3765-3773.

  7. Otero M, Lago R, Gómez R, Diéguez C, Lago F, Gómez-Reino J, et al. Towards a pro-inflammatory and immunomodulatory emerging role of leptin. Rheumatology 2006;45:944-950.

  8. Carlo AS, Pyrsky M, Loudes C, Faivre-Baumann A, Epelbaum J, Williams ML, et al. Leptin sensitivity in the developing rat hypothalamus. Endocrinology 2007;148:6073-6082.

  9. Wang M, Orci L, Ravazzola M, Unger RH. Fat storage in adipocytes requires inactivation of leptin’s paracrine activity: Implications for treatment of human obesity. PNAS 2005;102:18011-18016.

  10. Ravishankar RM, Beena G, Ragunathan P, Malathi R. Analysis of structure, function, and evolutionary origin of the ob gene product-leptin. J Biomol Struct Dyn 2007;25:183-188.

  11. Cui H, Cai F, Belsham DD. Leptin signaling in neurotensin neurons involves STAT, MAP kinases ERK1/2, and p38 through c-Fos and ATF1. FASEB J 2006;20:2654-2656.

  12. Noon LA, Clark AJ, O’Shaughnessy PJ, King PJ. A CCAAT/enhancerbinding protein site at -87 is required for the activation of a novel murine melanocortin 2-receptor promoter at late stages during adipogenesis. Endocrinology 2006;147:6019-6027.

  13. Lefebvre AM, Laville M, Vega N, Riou JP, Van Gaai L, Auwerx J, et al. Depot-specific differences in adipose tissue gene expression in lean and obese subjects. Diabetes 1998;47:98-103.

  14. Frühebeck G. Intracellular signaling pathways activated by leptin. Biochem J 2006;393:7-20.

  15. Prins JB. Adipose tissue as an endocrine organ. Best Prac Res Clin Endocrinol Metab 2002;16:639-651.

  16. Wauters M, Considine M, Van Gaal L. Human leptin: From an adipocyte hormone to an endocrine mediator. Eur J Endocrinol 2000;143:293-311.

  17. Kawachi H, Yang SH, Hamano A, Matsui T, Smith SB, Yano H. Molecular cloning and expression of bovine (Bos taurus) leptin receptor isoform mRNAs. Comp Biochem Physiol B Biochem Mol Biol 2007;148:167-173.

  18. Ziotopoulou M, Erani DM, Hileman SM, Bjorbaek C, Mantzoros CS. Unlike leptin, ciliary neurotrophic factor does not reverse the starvation-induced changes of serum corticosterone and hypothalamic neuropeptide levels but induces expression of hypothalamic inhibitors of leptin signaling. Diabetes 2000;49:1890-1896.

  19. Courtier C, Sarkis C, Séron K, Belouzard S, Chen P, Lenain A, et al. Silencing of OB-RGRP in mouse hypothalamic arcuate nucleus increases leptin receptor signaling and prevents diet-induced obesity. Proc Natl Acad Sci USA 2007;104:19476-19481.

  20. Tu H, Kastin AJ, Hsuchou H, Pan W. Soluble receptor inhibits leptin transport. J Cell Physiol 2008;214:301-305.

  21. Adachi H, Takemoto Y, Bungo T, Ohkubo T. Chicken leptin receptor is functional in activating JAK-STATpathway in vitro. J Endocrinol 2008;197:335- 342.

  22. Chen C, Chang YC, Liu CL, Liu TP, Chang KJ, Guo IC. Leptin induces proliferation and anti-apoptosis in human hepatocarcinoma cells by upregulating cyclin D1 and down-regulating Bax via a Janus kinase 2-linked pathway. Endocr Relat Cancer 2007;14:513-529.

  23. Bahrenberg G, Behrmann I, Barthel A, Hekerman P, Heinrich PC, Joost HG, et al. Identification of the critical sequence elements in the cytoplasmic domain of leptin receptor isoforms required for Janus kinase/signal transducer and activator of transcription activation by receptor heterodimers. Mol Endocrinol 2002;16:859-872.

  24. Lloyd RV, Jin L, Tsumanuma I, Vidal S, Kovacs K, Horvath E, et al. Leptin and leptin receptor in anterior pituitary function. Pituitary 2001;4:33-47.

  25. Czech MP, Covera S. Signaling mechanisms that regulated glucose transport. J Biol Chem 1999;274:1865-1868.

  26. Sahu A, Metlakunta AS. Hypothalamic phosphatidylinositol 3-kinase-phosphodiesterase 3B-cyclic AMP pathway of leptin signalling is impaired following chronic central leptin infusion. J Neuroendocrinol 2005;17:720-726.

  27. Faouzi M, Leshan R, Björnholm M, Hennessey T, Jones J, Münzberg H. Differential accessibility of circulating leptin to individual hypothalamic sites. Endocrinology 2007;148:5414-5423.

  28. Martínez JA, Aguado M, Frühbeck G. Interactions between leptin and NPY affecting lipid mobilization in adipose tissue. J Physiol Biochem 2000;56:1-8.

  29. Bray GA. Afferent signals regulating food intake. Proc Nutr Soc 2000;59:373- 384.

  30. Ahima RS. Central actions of adipocyte hormones. Trends in Endocrinol and Metabol 2005;16307-16313.

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

  32. Jequier E. Leptin signaling, adiposity, and energy balance. Ann N Y Acad Sci 2002;967:379-388.

  33. Tartaglia LA, Dembski M, Weng X, Deng N, Culpepper J, Devos R et al. Identification and expression cloning of a leptin receptor, OB-R. Cell 1995;83:1263-1271.

  34. Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D, et al. Weight-reducing effects of the plasma protein encoded by the obese gene. Science 1995;269:543-546.

  35. Arner P. Obesity —a genetic disease of adipose tissue? Br J Nutr 2000;83:S9- S16.

  36. Hebebrand J, Sommerlad C, Geller F, Görg T, Hinney A. The genetics of obesity: Practical implications. Int J Obes Relat Metab Disord 2001;25:S10- S18.

  37. Trayhurn P. Biology of leptin—its implications and consequences for the treatment of obesity. Int J Obes Relat Metab Disord 2001;25:S26-S28.

  38. Rosmond R. Association studies of genetic polymorphisms in central obesity: A critical review. Int J Obes Relat Metab Disord 2003;27:1141-1151.

  39. Tai ES, Lau TN, Ho SC, Fok AC, Tan CE. Body fat distribution and cardiovascular risk in normal weight women. Associations with insulin resistance, lipids and plasma leptin. J. Obes Relat Metab Disord 2000;24:751-757.

  40. Calle EE, Thun MJ. Obesity and cancer. Oncogene 2004;23:6365-6378.

  41. Kenchaiah S, Gaziano JM, Vasan RS. Impact of obesity on the risk of heart failure and survival after the onset of heart failure. Med Clin North Am 2004;88:1273-1294.

  42. Sowers JR. Obesity as a cardiovascular risk factor. Am J Med 2003;115:37S- 41S.

  43. Houseknecht KL, Baile CA, Matteri RL, Spurlock ME. The biology of leptin: A review. J Anim Sci 1998;76:1405-1420.

  44. Caro JF, Kolaczynski JW, Nyce MR, Ohannesian JP, Opentanova I, Goldman WH, et al. Decreased cerebrospinal-fluid/serum leptin ratio in obesity: A possible mechanism for leptin resistance. Lancet 1996;348:159-161.

  45. He Y, Chen H, Quon MJ, Reitman M. The mouse “obese” gene: genomic organization, promoter activity, and activation by CCAAT/enhancer-binding protein-alpha. J Biol Chem 1995;270:28887-28891.

  46. Ingalls AM, Dickie MM, Snell GD. Obese, a new mutation in the house mouse. J Hered 1950;41:317-318.

  47. Montague CT, Farooqi IS, Whitehead JP, Soos MA, Rau H, Wareham NJ, et al. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 1997;387:903-908.

  48. Echwald SM, Rasmussen SB, Sorensen TI, Andersen T, Tybjaerg-Hansen A, Clausen JO, et al. Identification of two novel missense mutations in the human OB gene. Int J Obes Relat Metab Disord 1997;21:321-326.

  49. Oksanen L, Kainulainen K, Heiman M, Mustajoki P, Kauppinen-Mäkelin R, Kontula K. Novel polymorphism of the human ob gene promoter in lean and morbidly obese subjects. Int J Obes Relat Metab Disord 1997;21:489-494.

  50. Unger RH, Orci L. Lipoapoptosis: Its mechanism and its diseases. Biochim Biophys Acta 2002;1585:202-212.

  51. Wang J, Obici S, Morgan K, Barzilai N, Feng Z, Rossetti L. Overfeeding rapidly induces leptin and insulin resistance. Diabetes 2001;50:2786-2791.

  52. Ceddia RB, Heikki AK, Zierath JR, Sweeney G. Analysis of paradoxical observations on the association between leptin and insulin resistance. FASEB J 2002;16:1163-1176.

  53. Morioka T, Asilmaz E, Hu J, Dishinger JF, Kurpad AJ, Elias CF, et al. Disruption of leptin receptor expression in the pancreas directly affects â?cell growth and function in mice. J Clin Invest 2007;117:2860-2868.

  54. Covey SD, Wideman RD, McDonald C, Unniappan S, Huynh F, Asadi A, et al. The pancreatic beta cell is a key site for mediating the effects of leptin on glucose homeostasis. Cell Metab 2006;4:291-302.

  55. Seufert J. Leptin effects on pancreatic beta-cell gene expression and function. Diabetes 2004;53:152-158.

  56. Brabant G, Müller G, Horn R, Anderwald C, Roden M, Nave H. Hepatic leptin signaling in obesity. FASEB J 2005;19:1048-1050.

  57. Cohen B, Novick D, Rubinstein M. Modulation of insulin activities by leptin. Science 1996;274:1185-1188.

  58. Fasshauer M, Paschke R. Regulation of adipocytokines and insulin resistance. Diabetologia 2003;46:1594-1603.

  59. Cruz M, García-Macedo R, García-Valerio Y, Gutiérrez M, Medina-Navarro R, Durán G, et al. Low adiponectin levels predict type 2 diabetes in Mexican children. Diabetes Care 2004;27:1451-1453.

  60. Hekerman P, Zeidler J, Korfmacher S, Bamberg-Lemper S, Knobelspies H, Zabeau L, et al. Leptin induces inflammation-related genes in RINm5F insulinoma cells. BMC Mol Biol 2007;23:41.

  61. Meier CA, Bobbioni E, Gabay C, Assimacopoulos-Jeannet F, Golay A, Dayer JM. IL-1 receptor antagonist serum levels are increased in human obesity: A possible link to the resistance to leptin? J Clin Endocrinol Metab, March 2002;87:1184-1188.

  62. Bruun JM, Pedersen SB, Kristensen K, Richelsen B. Effects of proinflammatory cytokines and chemokines on leptin production in human adipose tissue in vitro. Mol Cell Endocrinol 2002;190:91-99.

  63. Trujillo ME, Lee MJ, Sullivan S, Feng J, Schneider SH, Greenberg AS, et al. Tumor necrosis factor alpha and glucocorticoid synergistically increase leptin production in human adipose tissue: Role for p38 mitogen-activated protein kinase. J Clin Endocrinol Metab 2006;91:1484-1490.

  64. Zamora-Valdés D, Chávez-Tapia NC, Méndez-Sánchez N. Mecanismos moleculares de resistencia a la insulina. Medica Sur MG 2004;11:149-156.

  65. Paul H, Zeidler J, Korfmacher S, Bamberg-Lemper S, Knobelspies H, Zabeau L, Tavernier J, et al. Leptin induces inflammation-related genes in RINm5F insulinoma cells. BMC Molecular Biology 2007;8:41.

  66. Haynes WG. Interaction between leptin and sympathetic nervous system in hypertension. Current Hypertension Reports 2000;2:311-318.

  67. Matsumura K, Abe I, Tsuchihashi T, Fujishima M. Central effects of leptin on cardiovascular and neurohormonal responses in conscious rabbits. Am J Physiol. Reg Integ Comp Physiol 2000;278:R1314-1320.

  68. Shirasaka T, Takasaki M, Kannan H. Cardiovascular effects of leptin and orexins. Am J Physiol. Reg Integ Comp Physiol 2003;284:R639-R651.

  69. Correia ML, Morgan DA, Sivitz WI, Mark AL, Haynes WG. Leptin acts in the central nervous system to produce dose dependent changes in arterial pressure. Hypertension 2001;37:936-942.

  70. Coatmellec-Taglioni G, Ribiere C. Factors that influence the risk of hypertension in obese individuals. Curr Opin Nephrol Hypertens 2003;12:305-308.

  71. Yang D, Chen H, Wang X, Tian Z, Tang L, Zhang Z, et al. Association of polymorphisms of leptin gene with body weight and body sizes indexes in Chinese indigenous cattle. J Genet Genomics 2007;34:400-405.

  72. Stachowiak M, Mackowski M, Madeja Z, Szydlowski M, Buszka A, Kaczmarek P, et al. Polymorphism of the porcine leptin gene promoter and analysis of its association with gene expression and fatness traits. Biochem Genet 2007;45:245-253.

  73. Ellingrod VL, Bishop JR, Moline J, Lin YC, Miller del D. Leptin and leptin receptor gene polymorphisms and increases in body mass index (BMI) from olanzapine treatment in persons with schizophrenia. Psychopharmacol Bull 2007;40:57-62.

  74. Henry ML, Davidson LB, Wilson JE, McKenna BK, Scott SA, McDonagh PF, et al. Whole blood aggregation and coagulation in db/db and ob/ob mouse models of type 2 diabetes. Blood Coagul Fibrinolysis 2008;19:124-134.

  75. Segersvärd R, Tsai JA, Herrington MK, Wang F. Obesity alters cytokine gene expression and promotes liver injury in rats with acute pancreatitis. Obesity (Silver Spring) 2008;16:23-28.

  76. Nagata M, Susuki W, Iisuka S, Takeda S, Aburada M, Miyamoto K. Type 2 diabetes mellitus in obese mouse model induced by monosodium glutamate. Exp Anim 2006;55:109-115.

  77. Perello M, Gaillard RC, Chisari A, Spinedi E. Adrenal enucleation in MSGdamaged hyperleptinemic male rats transiently restores adrenal sensitivity to leptin. Neuroendocrinol 2003;78:176-184.

  78. Giovambattista A, Suescun MO, Nessralla CC, Franca LR, Spinedi E, Calandra RS. Modulatory effects of leptin on Leydig cell function of normal and hyperleptinemic rats. Neuroendocrinol 2003;78:270-279.

  79. Adams AC, Clapham JC, Wynick D, Speakman JR. Feeding behavior in galanin knockout mice supports a role of galanin in fat intake and preference. J Neuroendocrinol 2008;20:199-206.

>Revistas >Gaceta Médica de México >Año2008, No. 6

· Indice de Publicaciones 
· ligas de Interes 

Derechos Resevados 2019