Palabras clave
Historia de la Medicina
Leptina
Metabolismo
Obesidad
Síndrome Metabólico Diabetes
History of Medicine
Leptin
Metabolism
Obesity
Metabolic Syndrome
Cómo citar
Resumen
El tejido adiposo, es en definitiva un verdadero órgano, cuya función va mucho más allá del concepto clásico de una reserva lipídica, en tanto hoy los avances y hallazgos científicos han demostrado que es un tejido metabólico altamente activo, con funciones endocrinas y hemato-inmunológicas. Dentro de los mediadores hormonales de origen adipocitario que ha generado una verdadera revolución dentro de la biología y patobiología del Síndrome Metabólico(SM) sobresale la Leptina(LEP). Recientemente, se cumplieron 20 años del descubrimiento de este factor, de quien se tenía evidencia hipotética de su existencia, ya desde los experimentos clásicos de lesión hipotalámica asociada a adiposidad desarrollados en 1940 por los científicos A. W. Hetherington y S. W. Ranson en Northwestern University Medical School (Chicago, Illinois, USA). El objetivo de este breve escrito, es exponer la historia detrás del pensamiento científico que develó la existencia de la LEP, y efectuar un marco conceptual del presente y futuro de este mediador de comunicación celular.
Citas
Jácome Roca A. Historia de las hormonas-Más de un siglo de endocrinología-. Bogotá DC (Colombia): Academia Nacional de Medicina, 2007.
Medvei VC. A History of Endocrinology. New Yok(New York, USA): Springer, 2011(reimpresión de la primera edición de 1982).
Bordeu, Theophile DE. Recherches sur les maladies chroniques. París (Francia): Chez Ruault, libraire, rue de la Harpe, 1775.
Bernard, Claude. Leçons de physiologie expérimentale appliquée à la médecine, faites au collége de France: Cours du semestre d'hiver 1854- 1855. París (Francia): J.-B. Baillière et fils, 1855. https://doi.org/10.5962/bhl.title.1818
Addison, T. On the Constitutional and Local Effects of Disease of the of the suprarenal capsules. Londres (Inglaterra): Highley, 1855.
Brown-Sequard CE, D'arsonval A. De l'injection des extraits liquides provenant des glandes et des tissues de l'organisme comme méthod therapeutique." Comp Rend Neb Soc Biol 1891; 3:248-250.
Dorantes Álvarez LM, Medina Bravo P. Ernest Starling y el nacimiento de la Endocrinología. Bol Med Hosp Infant Mex 2005; 62: 307-9.
Henderson J. Ernest Starling and 'Hormones': an historical commentary. J Endocrinol 2005;184:5-10. https://doi.org/10.1677/joe.1.06000
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. https://doi.org/10.1038/372425a0
Ein Fall von Tumor der Hypophysis cerebri ohne Akromegalie (A case involving a tumor of the hypophysis cerebri without acromegaly). Wiener Klinische Rundschau 1901; 15: 833-836/906-908.
Zárate A, Saucedo R. La distrofia adiposo genital o Síndrome de Frohlich: su contribución al establecimiento de la neuroendocrinología. Gac Méd Méx Vol 2007; 143: 349-50.
Hetherington AW, Ranson SW 1940. Hypothalamic lesions and adiposity in the rat. Anatomical Record 1940: 78: 149-172. https://doi.org/10.1002/ar.1090780203
Kennedy GC. The hypothalamic control of food intake in rats. Proc R Soc Lond B Biol Sci 1950;137:535-49. https://doi.org/10.1098/rspb.1950.0065
Kennedy GC. Food intake, energy balance and growth. Br Med Bull 1966;22:216-20. https://doi.org/10.1093/oxfordjournals.bmb.a070476
Kennedy GC. Interactions between feeding behavior and hormones during growth. Ann N Y Acad Sci 1969;157:1049-61. https://doi.org/10.1111/j.1749-6632.1969.tb12936.x
Kennedy GC. The relation between the central control of appetite, growth and sexual maturation. Guys Hosp Rep 1969;118:315-27.
Kennedy GC. The hypothalamus and obesity. Proc R Soc Med 1966; 59:1276-7. https://doi.org/10.1177/003591576605901219
Kennedy GC. The regulation of food intake. Adv Psychosom Med 1972;7:91-9. https://doi.org/10.1159/000393296
Ingalls AM, Dickie MM, Snell GD. Obese, a new mutation in the house mouse. Journal of Heredity 1950; 41: 317-318. https://doi.org/10.1093/oxfordjournals.jhered.a106073
Hummel KP, Dickie MM, Coleman DL. Diabetes, a new mutation in the mouse. Science 1966;153:1127-8. https://doi.org/10.1126/science.153.3740.1127
Hervey GR. Hypothalamic lesions in parabiotic rats. Journal of Physiology 1957; 138: 15-16.
Hervey GR. The effects of lesions in the hypothalamus in parabiotic rats. Journal of Physiology 1959; 145: 336-352. https://doi.org/10.1113/jphysiol.1959.sp006145
Hervey GR. Control of appetite. Personal and departmental recollections. Appetite 2013;61:100-10. https://doi.org/10.1016/j.appet.2012.10.008
Coleman DL. Effects of parabiosis of obese with diabetes and normal mice. Diabetologia 1973;9:294-8. https://doi.org/10.1007/BF01221857
Masuzaki H, Ogawa Y, Isse N et al. Human obese gene expression. Adipocyte-specific expression and regional differences in the adipose tissue. Diabetes 1995;44:855-8. https://doi.org/10.2337/diab.44.7.855
Friedman JM, Leibel RL, Siegel DS et al. Molecular mapping of the mouse ob mutation. Genomics 1991;11:1054-62. https://doi.org/10.1016/0888-7543(91)90032-A
Geffroy S, De Vos P, Staels B, Duban B, Auwerx J, de Martinville B. Localization of the human OB gene (OBS) to chromosome 7q32 by fluorescence in situ hybridization. Genomics 1995;28:603-4. https://doi.org/10.1006/geno.1995.1201
Isse N, Ogawa Y, Tamura N, Masuzaki H et al. Structural organization and chromosomal assignment of the human obese gene. J Biol Chem 1995;270:27728-33. https://doi.org/10.1074/jbc.270.46.27728
Gross MB. Personal communication: http://www.omim.org/entry/164160?search=leptin&highlight=leptin En: Online Mendelian Inheritance McKusick(OMIM) by registered trademarks of the Johns Hopkins University. http://omim.org/
Tartaglia LA, Dembski M, Weng X, Deng N, Culpepper J, Devos R, Richards GJ, Campfield LA, Clark FT, Deeds J, Muir C, Sanker S, Moriarty A, Moore KJ, Smutko JS, Mays GG, Wool EA, Monroe CA, Tepper RI. Identification and expression cloning of a leptin receptor, OB-R. Cell 1995;83:1263-71. https://doi.org/10.1016/0092-8674(95)90151-5
Chung WK, Power-Kehoe L, Chua M, Leibel RL. Mapping of the OB receptor to 1p in a region of nonconserved gene order from mouse and rat to human. Genome Res 1996;6:431-8. https://doi.org/10.1101/gr.6.5.431
Winick JD, Stoffel M, Friedman JM. Identification of microsatellite markers linked to the human leptin receptor gene on chromosome 1. Genomics 1996;36:221-2. https://doi.org/10.1006/geno.1996.0455
Frühbeck G. Overview of Adipose Tissue and Its Role in Obesity and Metabolic Disorders. En: Yang K (Editor). Adipose Tissue Protocols. Second Edition. New Jersey (New York, USA): Humana Press/Springer Science+Business Media, LLC, 2008. p. 1-22. https://doi.org/10.1007/978-1-59745-245-8_1
Khor VK, Shen WJ, Kraemer FB. Lipid droplet metabolism. Curr Opin Clin Nutr Metab Care 2013;16:632-7. https://doi.org/10.1097/MCO.0b013e3283651106
Krahmer N, Farese RV Jr, Walther TC. Balancing the fat: lipid droplets and human disease. EMBO Mol Med 2013;5:905-15. https://doi.org/10.1002/emmm.201100671
Gross DA, Silver DL. Cytosolic lipid droplets: from mechanisms of fat storage to disease. Crit Rev Biochem Mol Biol 2014;49:304-26. https://doi.org/10.3109/10409238.2014.931337
Ohsaki Y, Suzuki M, Fujimoto T. Open questions in lipid droplet biology. Chem Biol 2014;21:86-96. https://doi.org/10.1016/j.chembiol.2013.08.009
Lehr S, Hartwig S, Sell H. Adipokines: a treasure trove for the discovery of biomarkers for metabolic disorders. Proteomics Clin Appli 2012;6:91-101. https://doi.org/10.1002/prca.201100052
Raucci R, Rusolo F, Sharma A et al. Functional and structural features of adipokine family. Cytokine 2013;61:1-14. https://doi.org/10.1016/j.cyto.2012.08.036
Waki H, Tontonoz P. Endocrine functions of adipose tissue. Annu Rev Pathol. 2007;2:31-56. https://doi.org/10.1146/annurev.pathol.2.010506.091859
Wozniak SE, Gee LL, Wachtel MS, Frezza EE. Adipose tissue: the new endocrine organ? A review article. Dig Dis Sci 2009;54:1847-56. https://doi.org/10.1007/s10620-008-0585-3
Adamczak M, Wiecek A. The adipose tissue as an endocrine organ. Semin Nephrol 2013; 33:2-13. https://doi.org/10.1016/j.semnephrol.2012.12.008
Huh JY, Park YJ, Ham M, Kim JB. Crosstalk between adipocytes and immune cells in adipose tissue inflammation and metabolic dysregulation in obesity. Mol Cells 2014;37:365-71. https://doi.org/10.14348/molcells.2014.0074
Grant RW, Dixit VD. Adipose tissue as an immunological organ. Obesity (Silver Spring). 2015 Mar;23 (3):512-8. https://doi.org/10.1002/oby.21003
Soumaya K. Molecular mechanisms of insulin resistance in diabetes. Adv Exp Med Biol 2012;771:240-51. https://doi.org/10.1007/978-1-4614-5441-0_19
Bergmann K, Sypniewska G. Diabetes as a complication of adipose tissue dysfunction. Is there a role for potential new biomarkers? Clin Chem Lab Med 2013;51:177-85. https://doi.org/10.1515/cclm-2012-0490
Kwon H, Pessin JE. Adipokines mediate inflammation and insulin resistance. Front Endocrinol (Lausanne) 2013;4:71. https://doi.org/10.3389/fendo.2013.00071
Leal VD, Mafra D. Adipokines in obesity. Clin Chim Acta 2013;419C:87-94. https://doi.org/10.1016/j.cca.2013.02.003
Blüher M, Mantzoros CS. From leptin to other adipokines in health and disease: facts and expectations at the beginning of the 21st century. Metabolism 2015;64:131-45. https://doi.org/10.1016/j.metabol.2014.10.016
Spritzer PM, Lecke SB, Satler F et al. Adipose tissue dysfunction, adipokines, and low-grade chronic inflammation in polycystic ovary syndrome. Reproduction 2015;149:R219-27. https://doi.org/10.1530/REP-14-0435
Abenavoli L, Peta V. Role of adipokines and cytokines in non-alcoholic fatty liver disease. Rev Recent Clin Trials 2014;9(3):134-40. https://doi.org/10.2174/1574887109666141216102458
Stojsavljević S, Gomerčić Palčić M, Virović Jukić L et al. Adipokines and proinflammatory cytokines, the key mediators in the pathogenesis of nonalcoholic fatty liver disease. World J Gastroenterol 2014;20:18070-91. https://doi.org/10.3748/wjg.v20.i48.18070
Booth A, Magnuson A, Fouts J et al. Adipose tissue, obesity and adipokines: role in cancer promotion. Horm Mol Biol Clin Investig 2015;21:57-74. https://doi.org/10.1515/hmbci-2014-0037
Ungefroren H, Gieseler F, Fliedner S et al. Obesity and cancer. Horm Mol Biol Clin Investig 2015;21:5-15. https://doi.org/10.1515/hmbci-2014-0046
Milner JJ, Beck MA. The impact of obesity on the immune response to infection. Proc Nutr Soc 2012;71:298-306. https://doi.org/10.1017/S0029665112000158
Mancuso P. Obesity and respiratory infections: does excess adiposity weigh down host defense? Pulm Pharmacol Ther 2013;26:412-9. https://doi.org/10.1016/j.pupt.2012.04.006
Magrone T, Jirillo E. Childhood obesity: immune response and nutritional approaches. Front Immunol 2015;6:76. https://doi.org/10.3389/fimmu.2015.00076
Abella V, Scotece M, Conde J et al. Adipokines, metabolic syndrome and rheumatic diseases. J Immunol Res 2014;2014:343746. https://doi.org/10.1155/2014/343746
Gremese E, Tolusso B, Gigante MR et al. Obesity as a risk and severity factor in rheumatic diseases (autoimmune chronic inflammatory diseases). Front Immunol 2014;5:576. https://doi.org/10.3389/fimmu.2014.00576
Kerekes G, Nurmohamed MT, González-Gay MA et al. Rheumatoid arthritis and metabolic syndrome. Nat Rev Rheumatol 2014;10:691-6. https://doi.org/10.1038/nrrheum.2014.121
Toussirot E, Aubin F, Dumoulin G. Relationships between Adipose Tissue and Psoriasis, with or without Arthritis. Front Immunol 2014;5:368. https://doi.org/10.3389/fimmu.2014.00368
Voiculescu VM, Lupu M, Papagheorghe L et al. Psoriasis and Metabolic Syndrome--scientific evidence and therapeutic implications. J Med Life 2014;7:468-71.
García Morán GA, Parra Medina R, García Cardona A, Quintero Ronderos P, Garavito Rodríguez E. Cytokines, chemokines and growth factors. En: Anaya JM, Shoenfeld Y, Rojas Villarraga et al (Editors). Autoimmunity-From bench to bedside-. Bogotá, DC (Colombia): Editorial Colegio Mayor de Nuestra Señora del Rosario, 2013. p. 133-68.
Friedman J. 20 YEARS OF LEPTIN: Leptin at 20: an overview. J Endocrinol 2014; 223: T1-T8. https://doi.org/10.1530/JOE-14-0405
Wada N, Hirako S, Takenoya F et al. Leptin and its receptors. J Chem Neuroanat 2014;61-62:191-9. https://doi.org/10.1016/j.jchemneu.2014.09.002
Münzberg H, Morrison CD. Structure, production and signaling of leptin. Metabolism 2015;64:13-23. https://doi.org/10.1016/j.metabol.2014.09.010
Peelman F, Zabeau L, Moharana K, Savvides SN, Tavernier J. 20 years of leptin: insights into signaling assemblies of the leptin receptor. J Endocrinol 2014;223:T9-23. https://doi.org/10.1530/JOE-14-0264
Park HK, Ahima RS. Leptin signaling. F1000Prime Rep 2014;6:73. https://doi.org/10.12703/P6-73
van Swieten MM, Pandit R, Adan RA et al. The neuroanatomical function of leptin in the hypothalamus. J Chem Neuroanat 2014;61-62:207-20. https://doi.org/10.1016/j.jchemneu.2014.05.004
Farooqi IS, O'Rahilly S. 20 years of leptin: human disorders of leptin action. J Endocrinol. 2014;223:T63-70. https://doi.org/10.1530/JOE-14-0480
Farooqi IS, Jebb SA, Langmack G et al. Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med 1999;341:879-84. https://doi.org/10.1056/NEJM199909163411204
Tsoukas MA, Farr OM, Mantzoros CS. Leptin in congenital and HIV-associated lipodystrophy. Metabolism 2015;64:47-59. https://doi.org/10.1016/j.metabol.2014.07.017
Crujeiras AB, Carreira MC, Cabia B et al. Leptin resistance in obesity: An epigenetic landscape. Life Sci. 2015 May 18. [Epub ahead of print]" https://doi.org/10.1016/j.lfs.2015.05.003