Keywords
leptina
obesidad
enfermedad cardiovascular
riesgo cardiometabólico
obesidad
enfermedad cardiovascular
riesgo cardiometabólico
How to Cite
Gómez, Ángela, Palacio, J., Jaramillo, A., & Rosero, R. (2018). Leptina: más que una adipocina, una herramienta para la comprensión de la obesidad y el riesgo cardiovascular. Revista Colombiana De Endocrinología, Diabetes &Amp; Metabolismo, 5(3), 28–32. https://doi.org/10.53853/encr.5.3.431
Abstract
La obesidad es considerada actualmente como la epidemia del siglo XXI. El acelerado aumento de la prevalencia y mortalidad a causa de enfermedades cardiovasculares establece un precedente histórico como problema de salud pública mundial. El aumento en la incidencia de obesidad y enfermedades crónicas (enfermedad coronaria, cáncer, diabetes), así como la frecuente consulta por este problema en la práctica clínica, han llevado a profundizar en el entendimiento del eslabón que las une. Existen numerosos factores neuroendocrinos responsables de la regulación del metabolismo energético. Sin embargo, la leptina es quizás el mediador más estudiado de este balance. Se ha asociado a vías de señalización que son comunes en estados proinflamatorios como la resistencia a la insulina en tejido adiposo y la ateromatosis a nivel de endotelio. Factores ambientales como el envejecimiento, las alteraciones en el sueño y trastornos psiquiátricos se relacionan con este “epifenómeno”, los cuales, a través de su efecto sobre el estado inflamatorio de la obesidad, repercuten en la homeostasis energética y el mantenimiento del peso corporal normal con impacto consecuente en el estado cardiometabólico del individuo según lo señalan numerosos estudios. El descubrimiento de nuevas vías de comunicación, la acción de citocinas y adipocinas en común y la redefinición del concepto de obesidad plantean un panorama promisorio hacia nuevos objetivos de riesgo cardiovascular asociados a obesidad. En este artículo se hará una revisión del papel de la leptina en la enfermedad cardiovascular y la obesidad a través de los mecanismos fisiopatológicos que comparten, con miras hacia la identificación temprana de riesgo cardiometabólico y el impacto en morbimortalidad asociada a adiposidad.
References
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12. Costa Gil JR. Spinedi E. La tormentosa relación entre la grasa y el desarrollo de la diabetes mellitus de tipo 2: Rev Argent Endocrinol Metab. 2017;54(3):109-123.
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21. Mantzoros CS. The role of leptin in human obesity and disease: a review of current evidence. Ann Intern Med. 1999; 130(8):671-680.
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27. Bays HE. Adiposopathy is “sick fat” a cardiovascular disease? J Am Coll Cardiol. 2011; 57(25):2461-73.
28. Brown NK, Zhou Z, Zhang J, Zeng R, Wu J, Eitzman DT, et al. Perivascular adipose tissue in vascular function and disease: A review of current research and animal models. Arterioscler Thromb Vasc Biol. 2014; 34:1621–30.
29. Wei Shen, ZiMian Wang, Mark Punyanita, Jianbo Lei, Ahmet Sinav, John G. Kral, et al. Adipose tissue quantification by imaging methods: a proposed classification. Obes Res 2003; 11:5-16.
30. Grant RW, Dixit VD. Adipose tissue as an immunological organ. Obesity (Silver Spring) 2015; 23:512-8.
31. Bays H. Adiposopathy, “sick fat,” Ockham’s razor, and resolution of the obesity paradox. Curr Atheroscler Rep. 2014; 16(5):409.
32. Farooqi IS, Jebb SA, Langmack G, Lawrence E, Cheetham CH, Prentice AM, et al. Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med 1999; 341:879-884
33. Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med. 1996; 334(5):292-5.
34. Hall JE, da Silva AA, do Carmo JM, Dubinion J, Hamza S, Munusamy S, et al. Obesity- induced hypertension: role of sympathetic nervous system, leptin, and melanocortins. J Biol Chem 2010; 285:17271-6.
35. Ferrannini E, Camastra S, Gastaldelli A, Maria Sironi A, Natali A, Muscelli E, et al. Beta-cell function in obesity: ef- fects of weight loss. Diabetes 2004; 53:Suppl 3:S26- S33.
36. Wu J, Cohen P, Spiegelman BM. Adaptive thermogenesis in adipocytes: Is beige the new brown? Genes Dev. 2013; 27(3):234-50.
37. Tchkonia T, Thomou T, Zhu Y, Karagiannides I, Pothoulakis C, Jensen MD, et al. Mech- anisms and metabolic implications of regional differences among fat depots. Cell Metab 2013; 17:644-56.
38. Fitzgibbons TP, Czech MP. Epicardial and perivascular adipose tissues and their influence on cardiovascular disease: basic mechanisms and clinical associations. J Am Heart Assoc. 2014; 3(2):e000582.
39. Harms M, Seale P. Brown and beige fat: development, function and therapeutic potential. Nature medicine. 2013. p. 1252-63.
40. McGown C, Birerdinc A, Younossi ZM. Adipose Tissue as an Endocrine Organ. Clin Liver Dis. 2014; 18(1):41-58.
41. Padilla J, Jenkins NT, Vieira-Potter VJ, Laughlin MH. Divergent phenotype of rat thoracic and abdominal perivascular adipose tissues. Am J Physiol Regul Integr Comp Physiol. 2013; 304(7).
42. Crewe C, An YA, et al. The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. J Clin Invest. 2017; 127 (1):74-82.
43. Schipper HS, Prakken B, Kalkhoven E, Boes M. Adipose tissue-resident immune cells: key players in immunometabolism. Trends Endocrinol Metab 2012; 23(8):407-415.
44. Daniel A. Winer, Shawn Winer, Lei Shen, Persis P. Wadia Jason Yantha, Geoffrey Paltser, et al. B cells promote insulin resistance through modula-tion of T Cells and production of pathogenic IgG antibodies. Nat Med. 2011; 17(5):610-617.
45. Li J, Yu X, Pan W, Unger RH. Gene expression profile of rat adipose tissue at the onset of high fat-diet obesity. Am J Physiol Endocrinol Metab. 2002; 282(6): E1334-E1341.
46. Calle EE, Thun MJ. Obesity and cancer. Oncogene 2004; 23:6365-78.
47. Kaur J. A comprehensive review on metabolic syndrome. Cardiol Res Pract 2014; 2014:943162.
48. McCullough AJ. The clinical features, diagnosis and natural history of non- alcoholic fatty liver disease. Clin Liver Dis 2004; 8:521-33.
49. Kettner NM, Mayo SA, Hua J, Lee Ch, Moore DD, Fu L. Circadian Dysfunction Induces Leptin Resistance in Mice. 2015, Cell Metabolism 22, 448-459.
50. Santillán Benítez JG, Mendieta Zerón H, Ordóñez Quiroz Á. La leptina en la carcinogénesis mamaria. Vías de señalización. Rev Química Viva. 2012; 11(2):91-111.
51. Ernst MB, Wunderlich CM, Hess S, Paehler M, Mesaros A, Koralov SB, et al. Enhanced Stat3 activation in POMC neurons provokes negative feed-back inhibition of leptin and insulin signaling in obesity. J Neurosci. 2009 Sep 16; 29 (37): 11582-93.
52. Gong L, Yao F, Hockman K, Heng HH, Morton GJ, Takeda K,et al. Signal transducer and activator of transcription-3 is required in hypothalamic agouti- related protein/ neuropeptide Y neurons for normal energy homeostasis. Endocrinology. 2008; 149(7):3346-54.
53. Vásquez MEF. Señalización de la leptina. REB 25(2):50-4, 2006.
54. Morrison CD. Leptin signaling in brain: A link between nutrition and cognition? Biochimica et Biophysica Acta. 2009; 1792(5):401-8.
55. The GBD obesity Collaborators, Health Effects of Overweight and Obesity in 195 Countries over 25 Years, N Engl J Med 2017; 377:13-27.
2. Hall KD, Guo J, Dore M, Chow CC. The progressive increase of food waste in America and its environmental impact. PLoS One 2009; 4(11):E7940
3. Simón EL BAS. Leptina y obesidad. Anales del sistema sanitario de Navarra. 2002; 25:53-64.
4. Popkin BM, Hawkes C. Sweeting of the global diet, particularly beverages: patterns, trends, and policy responses. J. Diabetes Endocrinol 2016; 4:174-86.
5. Church TS1, Thomas DM, Tudor-Locke C, Katzmarzyk PT, Earnest CP, Rodarte RQ, et.al. Trends over 5 decades in U.S. occupation-related physical activity and their associations with obesity. PLoS One 2011;6(5):e19657.
6. Von Loeffelholz C. The Role Non-Exercise Activity Thermogenesis in Human Obesity. In: De Groot LJ, ed. Endotext. South Darmouth, MA: MDText.com, 2000.
7. McAllister EJ, Dhurandhar NV, Keith SW, et al. Ten putative contributors to the obesity epidemic. Crit Rev Food Sci Nutr 2009; 49:868-913.
8. Heymsfiel SB, Wadden TA. Mechanisms, Pathophysiology, and Management of Obesity. N Engl J Med 2017; 376:254-66.
9. Akbaraly TN, Kivimaki M, Ancelin ML, et al. Metabolic syndrome,its components, and mortality in the elderly. J Clin Endocrinol Metab. 2010; 95(11):E327-E332.
10. Pasco JA, Henry MJ, Kotowicz MA, Collier GR, Ball MJ, Ugoni AM, et al. Serum leptin levels are associated with bone mass in nonobese women. J Clin Endocrinol Metab 2001;86(5):1884-7.
11. Rosero, R. Sierra A, Medina A. Interacción de la Leptina y hueso en sujetos obesos. Protección vs Fragilidad. Rev Col Endo Dia y Metabol 2015; 2(3):14-21.
12. Costa Gil JR. Spinedi E. La tormentosa relación entre la grasa y el desarrollo de la diabetes mellitus de tipo 2: Rev Argent Endocrinol Metab. 2017;54(3):109-123.
13. Paduszy?ski W, Je?kiewicz M, Ucha?ski P, Gackowski S, Radkowski M, Demkow U, Hoffa´s fat pad abnormality in the development of knee osterarthiritis. Adv Exp Med Biol. 2017 Aug 3. doi: 10.1007/5584_2017_77.
14. Health United States, 2015: with special feature on racial and ethnic health disparities. Hyattsville, MD: Centers for Disease Control and Prevention, National Center for Health Statistics, 2016:461.
15. Lieb W, Sullivan LM, Harris TB, et al. Plasma leptin levels and incidence of heart failure, cardiovascular disease, and total mortality in elderly individuals. Diabetes Care 2009; 32(4):612-616.
16. Welsh P, Murray HM, Buckley BM, et al. Leptin predicts diabetes but not cardiovascular disease: results from a large prospective study in an elderly population. Diabetes Care. 2009; 32(2):308-310.
17. Batsis JA, Sahakyan KR, Singh P, Bartels SJ, Somers VK. Leptin, Adiposity, and Mortaity: Results from the National Health and Nutrition Examination Survey III, 1988 to 1994. Mayo Foundation for Medical Education and Research, Mayo Clin Proc. 2015; 90(4):481-491.
18. Dardeno TA, Chou SH, Moon HS, Chamberland JP, Fiorenza CG, Man-tzoros CS. Leptin in human physiology and therapeutics. Frontiers in neuroendocrinology. 2010; 31(3):377-93.
19. 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(7):1263-71.
20. Friedman JM. Leptin, leptin receptors, and the control of body weight. Na-ture. 1998 Oct 22;395(6704):763-70.
21. Mantzoros CS. The role of leptin in human obesity and disease: a review of current evidence. Ann Intern Med. 1999; 130(8):671-680.
22. Eiva Bernotiene, Gaby Palmer, Cem Gabay. The role of leptin in innate and adaptative immune responses. Arthritis Res Ther. 2006; 8(5): 217.
23. Bjorbaek C, Elmquist JK, Michl P, Ahima RS, van Bueren A, McCall AL, et al. Expression of leptin receptor isoforms in rat brain microvessels. Endocrinology. 1998; 139(8):3485-91. Epub 1998/07/29.
24. Myers MG. Jr. Leptin Keeps Working, Even in Obesity. Cell Metabolism Volume 21, Issue 6, 2 June 2015, Pages 791-792.
25. Bray MS, Loos RJ, McCaffery JM, Ling C, Franks PW, Weinstock GM, et al. NIH working group report-using genomic information to guide weight management: from uni- versal to precision treatment. Obesity (Silver Spring) 2016; 24:14-22.
26. Heymsfiel SB, Gonzalez MC, Shen W, Redman L, Thomas D. Weight loss composition is one fourth fat-free mass: a critical review and critique of this widely cited rule. Obes Rev 2014; 15:310-21.
27. Bays HE. Adiposopathy is “sick fat” a cardiovascular disease? J Am Coll Cardiol. 2011; 57(25):2461-73.
28. Brown NK, Zhou Z, Zhang J, Zeng R, Wu J, Eitzman DT, et al. Perivascular adipose tissue in vascular function and disease: A review of current research and animal models. Arterioscler Thromb Vasc Biol. 2014; 34:1621–30.
29. Wei Shen, ZiMian Wang, Mark Punyanita, Jianbo Lei, Ahmet Sinav, John G. Kral, et al. Adipose tissue quantification by imaging methods: a proposed classification. Obes Res 2003; 11:5-16.
30. Grant RW, Dixit VD. Adipose tissue as an immunological organ. Obesity (Silver Spring) 2015; 23:512-8.
31. Bays H. Adiposopathy, “sick fat,” Ockham’s razor, and resolution of the obesity paradox. Curr Atheroscler Rep. 2014; 16(5):409.
32. Farooqi IS, Jebb SA, Langmack G, Lawrence E, Cheetham CH, Prentice AM, et al. Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med 1999; 341:879-884
33. Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med. 1996; 334(5):292-5.
34. Hall JE, da Silva AA, do Carmo JM, Dubinion J, Hamza S, Munusamy S, et al. Obesity- induced hypertension: role of sympathetic nervous system, leptin, and melanocortins. J Biol Chem 2010; 285:17271-6.
35. Ferrannini E, Camastra S, Gastaldelli A, Maria Sironi A, Natali A, Muscelli E, et al. Beta-cell function in obesity: ef- fects of weight loss. Diabetes 2004; 53:Suppl 3:S26- S33.
36. Wu J, Cohen P, Spiegelman BM. Adaptive thermogenesis in adipocytes: Is beige the new brown? Genes Dev. 2013; 27(3):234-50.
37. Tchkonia T, Thomou T, Zhu Y, Karagiannides I, Pothoulakis C, Jensen MD, et al. Mech- anisms and metabolic implications of regional differences among fat depots. Cell Metab 2013; 17:644-56.
38. Fitzgibbons TP, Czech MP. Epicardial and perivascular adipose tissues and their influence on cardiovascular disease: basic mechanisms and clinical associations. J Am Heart Assoc. 2014; 3(2):e000582.
39. Harms M, Seale P. Brown and beige fat: development, function and therapeutic potential. Nature medicine. 2013. p. 1252-63.
40. McGown C, Birerdinc A, Younossi ZM. Adipose Tissue as an Endocrine Organ. Clin Liver Dis. 2014; 18(1):41-58.
41. Padilla J, Jenkins NT, Vieira-Potter VJ, Laughlin MH. Divergent phenotype of rat thoracic and abdominal perivascular adipose tissues. Am J Physiol Regul Integr Comp Physiol. 2013; 304(7).
42. Crewe C, An YA, et al. The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. J Clin Invest. 2017; 127 (1):74-82.
43. Schipper HS, Prakken B, Kalkhoven E, Boes M. Adipose tissue-resident immune cells: key players in immunometabolism. Trends Endocrinol Metab 2012; 23(8):407-415.
44. Daniel A. Winer, Shawn Winer, Lei Shen, Persis P. Wadia Jason Yantha, Geoffrey Paltser, et al. B cells promote insulin resistance through modula-tion of T Cells and production of pathogenic IgG antibodies. Nat Med. 2011; 17(5):610-617.
45. Li J, Yu X, Pan W, Unger RH. Gene expression profile of rat adipose tissue at the onset of high fat-diet obesity. Am J Physiol Endocrinol Metab. 2002; 282(6): E1334-E1341.
46. Calle EE, Thun MJ. Obesity and cancer. Oncogene 2004; 23:6365-78.
47. Kaur J. A comprehensive review on metabolic syndrome. Cardiol Res Pract 2014; 2014:943162.
48. McCullough AJ. The clinical features, diagnosis and natural history of non- alcoholic fatty liver disease. Clin Liver Dis 2004; 8:521-33.
49. Kettner NM, Mayo SA, Hua J, Lee Ch, Moore DD, Fu L. Circadian Dysfunction Induces Leptin Resistance in Mice. 2015, Cell Metabolism 22, 448-459.
50. Santillán Benítez JG, Mendieta Zerón H, Ordóñez Quiroz Á. La leptina en la carcinogénesis mamaria. Vías de señalización. Rev Química Viva. 2012; 11(2):91-111.
51. Ernst MB, Wunderlich CM, Hess S, Paehler M, Mesaros A, Koralov SB, et al. Enhanced Stat3 activation in POMC neurons provokes negative feed-back inhibition of leptin and insulin signaling in obesity. J Neurosci. 2009 Sep 16; 29 (37): 11582-93.
52. Gong L, Yao F, Hockman K, Heng HH, Morton GJ, Takeda K,et al. Signal transducer and activator of transcription-3 is required in hypothalamic agouti- related protein/ neuropeptide Y neurons for normal energy homeostasis. Endocrinology. 2008; 149(7):3346-54.
53. Vásquez MEF. Señalización de la leptina. REB 25(2):50-4, 2006.
54. Morrison CD. Leptin signaling in brain: A link between nutrition and cognition? Biochimica et Biophysica Acta. 2009; 1792(5):401-8.
55. The GBD obesity Collaborators, Health Effects of Overweight and Obesity in 195 Countries over 25 Years, N Engl J Med 2017; 377:13-27.
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