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2009, Número 2

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Bioquimia 2009; 34 (2)


La tormenta perfecta: obesidad, disfunción del adipocito y consecuencias metabólicas

Ferranti S, Mozaffarian D, Sánchez RMA

Idioma: Español
Referencias bibliográficas: 95
Paginas: 95-108
Archivo PDF: 143.61 Kb.


RESUMEN

Antecedentes: La apreciación de la cercanía entre la obesidad y la enfermedad se ha incrementado dada la elevación de la prevalencia de obesidad en países desarrollados y en vías de desarrollo. La fuerte relación entre el exceso de tejido adiposo y pobres resultados en la salud, incluyendo enfermedad cardiovascular, diabetes y cáncer, demandan la elucidación de la fisiopatología celular compleja, hormonal y molecular según la cual la adiposidad inicia y mantiene los efectos adversos a la salud. Contenido: En este reporte revisamos el metabolismo del adipocito y su función en el contexto del desequilibrio energético y el exceso de nutrientes postprandiales, incluyendo la hipertrofia e hiperplasia del adipocito, la disfunción del adipocito y otras consecuencias sistémicas. Discutimos también las implicaciones para la evaluación del laboratorio y el cuidado clínico, incluyendo el papel de las modificaciones del estilo de vida. El desequilibrio energético crónico produce hipertrofia e hiperplasia del adipocito, estrés del retículo endoplásmico y disfunción mitocondrial. Este proceso deja una liberación intracelular y sistémica incrementada de adipocinas, ácidos grasos libres y mediadores inflamatorios que causan disfunción del adipocito e inducen efectos adversos en las células hepáticas, pancreáticas y del músculo esquelético, además de los lechos cardiaco y vascular. Varias pruebas especializadas de laboratorio pueden cuantificar estos procesos y predecir un riesgo clínico, pero la traducción a la clínica es prematura. Intervenciones farmacológicas actuales y a futuro pueden tener como blanco estas vías; probablemente modestos cambios en la dieta, actividad física, peso y tabaquismo tienen gran impacto. Resumen: El estrés del retículo endoplásmico y mitocondrial del adipocito, y los cambios asociados en la circulación de adipocinas, ácidos grasos libres y mediadores inflamatorios son el centro de los efectos adversos a la salud de la adiposidad. Investigaciones futuras pueden enfocarse en estas vías y en revertir los comportamientos adversos del estilo de vida que son la causa fundamental de la adiposidad.


REFERENCIAS (EN ESTE ARTÍCULO)

  1. Lyon HN, Hirschhorn JN. Genetics of common forms of obesity: a brief overview. Am J Clin Nutr. 2005; 82: 215S- 7S.

  2. Taheri S, Lin L, Austin D, Young T, Mignot E. Short sleep duration is associated with reduced leptin, elevated ghrelin, and increased body mass index. PLoS Med. 2004; 1: e62.

  3. Cheskin LJ. The pathogens are speaking: are we listening? J Nutr. 2001; 131: 2809S-10S.

  4. Kavanagh K, Jones KL, Sawyer J, Kelley K, Carr JJ, Wagner JD, Rudel LL. Trans fat diet induces abdominal obesity and changes in insulin sensitivity in monkeys. Obesity. (Silver Spring) 2007; 15: 1675-84.

  5. Oken E, Gillman MW. Fetal origins of obesity. Obes Res. 2003; 11: 496-506.

  6. Thomas DE, Elliott EJ, Baur L. Low glycaemic index or low glycaemic load diets for overweight and obesity. Cochrane Database Syst Rev. 2007; CD005105.

  7. Bahceci M, Gokalp D, Bahceci S, Tuzcu A, Atmaca S, Arikan S. The correlation between adiposity and adiponectin, tumor necrosis factor alpha, interleukin-6 and high sensitivity C-reactive protein levels. Is adipocyte size associated with inflammation in adults? J Endocrinol Invest. 2007; 30: 210-4.

  8. Avram MM, Avram AS, James WD. Subcutaneous fat in normal and diseased states 3. Adipogenesis: from stem cell to fat cell. J Am Acad Dermatol. 2007; 56: 472-92.

  9. Drolet R, Richard C, Sniderman AD, Mailloux J, Fortier M, Huot C, et al. Hypertrophy and hyperplasia of abdominal adipose tissues in women. Int J Obes. (Lond) 2008; 32: 283-91.

  10. Tontonoz P, Hu E, Spiegelman BM. Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor. Cell. 1994; 79: 1147-56.

  11. Larsen TM, Toubro S, Astrup A. PPARgamma agonists in the treatment of type II diabetes: is increased fatness commensurate with long-term efficacy? Int J Obes Relat Metab Disord. 2003; 27: 147-61.

  12. Hirsch J, Fried SK, Edens NK, Leibel RL. The fat cell. Med Clin North Am. 1989; 73: 83-96.

  13. Bjorntorp P, Karlsson M, Pettersson P. Expansion of adipose tissue storage capacity at different ages in rats. Metabolism. 1982; 31: 366-73.

  14. Fox CS, Massaro JM, Hoffmann U, Pou KM, Maurovich- Horvat P, Liu CY, et al. Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study. Circulation. 2007; 116: 39-48.

  15. Harman-Boehm I, Bluher M, Redel H, Sion-Vardy N, Ovadia S, Avinoach E, et al. Macrophage infiltration into omental versus subcutaneous fat across different populations: effect of regional adiposity and the comorbidities of obesity. J Clin Endocrinol Metab. 2007; 92: 2240-7.

  16. Gregor MF, Hotamisligil GS. Thematic review series: Adipocyte Biology. Adipocyte stress: the endoplasmic reticulum and metabolic disease. J Lipid Res. 2007; 48: 1905-14.

  17. Hosogai N, Fukuhara A, Oshima K, Miyata Y, Tanaka S, Segawa K, et al. Adipose tissue hypoxia in obesity and its impact on adipocytokine dysregulation. Diabetes. 2007; 56: 901-11.

  18. Su Q, Wang S, Gao HQ, Kazemi S, Harding HP, Ron D, Koromilas AE. Modulation of the eukaryotic initiation factor 2 {alpha}-subunit kinase PERK by tyrosine phosphorylation. J Biol Chem. 2008; 283: 469-75.

  19. Hirosumi J, Tuncman G, Chang L, Gorgun CZ, Uysal KT, Maeda K, et al. A central role for JNK in obesity and insulin resistance. Nature. (Lond) 2002; 420: 333-6.

  20. Aguirre V, Uchida T, Yenush L, Davis R, White MF. The c-Jun NH(2)-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser(307). J Biol Chem. 2000; 275: 9047-54.

  21. Waeber G, Delplanque J, Bonny C, Mooser V, Steinmann M, Widmann C, et al. The gene MAPK8IP1, encoding isletbrain- 1, is a candidate for type 2 diabetes. Nat Genet. 2000; 24: 291-95.

  22. Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes. 2003; 52: 102-10.

  23. Kaneto H, Nakatani Y, Kawamori D, Miyatsuka T, Matsuoka TA, Matsuhisa M, Yamasaki Y. Role of oxidative stress, endoplasmic reticulum stress, and c-Jun N-terminal kinase in pancreatic beta-cell dysfunction and insulin resistance. Int J Biochem Cell Biol. 2006; 38: 782-93.

  24. Wojtczak L, Schonfeld P. Effect of fatty acids on energy coupling processes in mitochondria. Biochim Biophys Acta. 1993; 1183: 41-57.

  25. Fridlyand LE, Philipson LH. Reactive species and early manifestation of insulin resistance in type 2 diabetes. Diabetes Obes Metab. 2006; 8: 136-45.

  26. Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y, et al. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest. 2004; 114: 1752-61.

  27. Eizirik DL, Cardozo AK, Cnop M. The role for endoplasmic reticulum stress in diabetes mellitus. Endocr Rev 2008; 29: 42-61.

  28. Evans JL, Goldfine ID, Maddux BA, Grodsky GM. Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes. Endocr Rev. 2002; 23: 599-622.

  29. Qatanani M, Lazar MA. Mechanisms of obesity associated insulin resistance: many choices on the menu. Genes Dev. 2007; 21: 1443-55.

  30. Petersen KF, Befroy D, Dufour S, Dziura J, Ariyan C, Rothman DL, et al. Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science. (Wash DC) 2003; 300: 1140-42.

  31. Marfella R, Verrazzo G, Acampora R, La Marca C, Giunta R, Lucarelli C, et al. Glutathione reverses systemic hemodynamic changes induced by acute hyperglycemia in healthy subjects. Am J Physiol. 1995; 268: E1167-E1173.

  32. Imoto K, Kukidome D, Nishikawa T, Matsuhisa T, Sonoda K, Fujisawa K, et al. Impact of mitochondrial reactive oxy gen species and apoptosis signal-regulating kinase 1 on insulin signaling. Diabetes. 2006; 55: 1197-204.

  33. Houstis N, Rosen ED, Lander ES. Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature. (Lond) 2006; 440: 944-8.

  34. Tilg H, Moschen AR. Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol. 2006; 6: 772-83.

  35. Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, et al. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun. 1999; 257: 79-83.

  36. Hotta K, Funahashi T, Arita Y, Takahashi M, Matsuda M, Okamoto Y, et al. Plasma concentrations of a novel, adipose- specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol. 2000; 20: 1595-9.

  37. Campbell PJ, Carlson MG, Nurjhan N. Fat metabolism in human obesity. Am J Physiol. 1994; 266: E600-E605.

  38. Schaffer JE. Lipotoxicity: when tissues overeat. Curr Opin Lipidol. 2003; 14: 281-7.

  39. Boden G. Fatty acid-induced inflammation and insulin resistance in skeletal muscle and liver. Curr Diab Rep. 2006; 6: 177-81.

  40. Yu YH, Ginsberg HN. Adipocyte signaling and lipid homeostasis: sequelae of insulin-resistant adipose tissue. Circ Res. 2005; 96: 1042-52.

  41. Lupi R, Dotta F, Marselli L, Del Guerra S, Masini M, Santangelo C, et al. Prolonged exposure to free fatty acids has cytostatic and pro-apoptotic effects on human pancreatic islets: evidence that beta-cell death is caspase mediated, partially dependent on ceramide pathway, and Bcl-2 regulated Diabetes. 2002; 51: 1437-42.

  42. Yudkin JS. Inflammation, obesity, and the metabolic syndrome. Horm Metab Res. 2007; 39: 707-9.

  43. Nishimura F, Iwamoto Y, Mineshiba J, Shimizu A, Soga Y, Murayama Y. Periodontal disease and diabetes mellitus: the role of tumor necrosis factor-alpha in a 2-way relationship. J Periodontol. 2003; 74: 97-102.

  44. Mohamed-Ali V, Goodrick S, Rawesh A, Katz DR, Miles JM, Yudkin JS, et al. Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-alpha, in vivo. J Clin Endocrinol Metab. 1997; 82: 4196-200.

  45. Kern PA, Saghizadeh M, Ong JM, Bosch RJ, Deem R, Simsolo RB. The expression of tumor necrosis factor in human adipose tissue: regulation by obesity, weight loss, and relationship to lipoprotein lipase. J Clin Invest 1995; 95: 2111-9.

  46. Miyazaki Y, Pipek R, Mandarino LJ, DeFronzo RA. Tumor necrosis factor alpha and insulin resistance in obese type 2 diabetic patients. Int J Obes Relat Metab Disord. 2003; 27: 88-94.

  47. Yang Q, Graham TE, Mody N, Preitner F, Peroni OD, Zabolotny JM, et al. Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature. (Lond) 2005; 436: 356-62.

  48. Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesitylinked insulin resistance. Science. (Wash DC) 1993; 259: 87-91.

  49. Picchi A, Gao X, Belmadani S, Potter BJ, Focardi M, Chilian WM, Zhang C. Tumor necrosis factor alpha induces endothelial dysfunction in the prediabetic metabolic syndrome. Circ Res. 2006; 99: 69-77.

  50. Guzik TJ, Mangalat D, Korbut R. Adipocytokines: novel link between inflammation and vascular function? J Physiol Pharmacol. 2006; 57: 505-28.

  51. Wolf G. Serum retinol-binding protein: a link between obesity, insulin resistance, and type 2 diabetes. Nutr Rev. 2007; 65: 251-6.

  52. Lee JW, Im JA, Lee HR, Shim JY, Youn BS, Lee DC. Visceral adiposity is associated with serum retinol binding protein- 4 levels in healthy women. Obesity. (Silver Spring) 2007; 15: 2225-32.

  53. Jia W, Wu H, Bao Y, Wang C, Lu J, Zhu J, Xiang K. Association of serum retinol-binding protein 4 and visceral adiposity in Chinese subjects with and without type 2 diabetes. J Clin Endocrinol Metab. 2007; 92: 3224-9.

  54. Graham TE, Yang Q, Bluher M, Hammarstedt A, Ciaraldi TP, Henry RR, et al. Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects. N Engl J Med. 2006; 354: 2552-63.

  55. Janke J, Engeli S, Boschmann M, Adams F, Bohnke J, Luft FC, et al. Retinol-binding protein 4 in human obesity. Diabetes. 2006; 55: 2805-10.

  56. Takashima N, Tomoike H, Iwai N. Retinol-binding protein 4 and insulin resistance. N Engl J Med. 2006; 355: 1392-5.

  57. Erikstrup C, Mortensen OH, Pedersen BK. Retinol binding protein 4 and insulin resistance. N Engl J Med. 2006; 355: 1393-4.

  58. Balagopal P, Graham TE, Kahn BB, Altomare A, Funanage V, George D. Reduction of elevated serum retinol binding protein in obese children by lifestyle intervention: association with subclinical inflammation. J Clin Endocrinol Metab. 2007; 92: 1971-4.

  59. Aeberli I, Biebinger R, Lehmann R, L’allemand D, Spinas GA, Zimmermann MB. Serum retinol-binding protein 4 concentration and its ratio to serumretinol are associated with obesity and metabolic syndrome components in children. J Clin Endocrinol Metab. 2007; 92: 4359-65.

  60. Park HS, Park JY, Yu R. Relationship of obesity and visceral adiposity with serum concentrations of CRP, TNF-alpha and IL-6. Diabetes Res Clin Pract. 2005; 69: 29-35.

  61. Mohamed-Ali V, Pinkney JH, Coppack SW. Adipose tissue as an endocrine and paracrine organ. Int J Obes Relat Metab Disord. 1998; 22: 1145-58.

  62. Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon RO, III, Criqui M, et al. Markers of inflammation and cardiovascular disease: application to clinical and public health practice. A statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation. 2003; 107: 499-511.

  63. Cook DG, Mendall MA, Whincup PH, Carey IM, Ballam L, Morris JE, et al. C-reactive protein concentration in children: relationship to adiposity and other cardiovascular risk factors. Atherosclerosis. 2000; 149: 139-50.

  64. Haddy N, Sass C, Droesch S, Zaiou M, Siest G, Ponthieux A, et al. IL-6, TNF-alpha and atherosclerosis risk indicators in a healthy family population: the STANISLAS cohort. Atherosclerosis. 2003; 170: 277-83.

  65. Diez-Ruiz A, Tilz GP, Zangerle R, Baier-Bitterlich G, Wachter H, Fuchs D. Soluble receptors for tumour necrosis factor in clinical laboratory diagnosis. Eur J Haematol. 1995; 54: 1-8.

  66. #176270 Prader-Willi syndrome. http://www.ncbi.nlm.nih.gov/ entrez/dispomim.cgi? id_176270. Accessed: April 17, 2008.

  67. Hansen JS, Villadsen JK, Gaster M, Faergeman NJ, Knudsen J. Micro method for determination of nonesterified fatty acid in whole blood obtained by fingertip puncture. Anal Biochem. 2006; 355: 29-38.

  68. Pilz S, Scharnagl H, Tiran B, Seelhorst U, Wellnitz B, Boehm BO, et al. Free fatty acids are independently asso ciated with all-cause and cardiovascular mortality in subjects with coronary artery disease. J Clin Endocrinol Metab. 2006; 91: 2542-7.

  69. Wu LL, Chiou CC, Chang PY, Wu JT. Urinary 8-OHdG: a marker of oxidative stress to DNA and a risk factor for cancer, atherosclerosis and diabetics. Clin Chim Acta. 2004; 339: 1-9.

  70. Ashfaq S, Abramson JL, Jones DP, Rhodes SD, Weintraub WS, Hooper WC, et al. The relationship between plasma levels of oxidized and reduced thiols and early atherosclerosis in healthy adults. J Am Coll Cardiol. 2006; 47: 1005-11.

  71. Hsueh WA, Bruemmer D. Peroxisome proliferator activated receptor gamma: implications for cardiovascular disease. Hypertension. 2004; 43: 297-305.

  72. Johansen JS, Harris AK, Rychly DJ, Ergul A. Oxidative stress and the use of antioxidants in diabetes: linking basic science to clinical practice. Cardiovasc Diabetol. 2005; 4: 5.

  73. Kris-Etherton PM, Lichtenstein AH, Howard BV, Steinberg D, Witztum JL. Antioxidant vitamin supplements and cardiovascular disease. Circulation. 2004; 110: 637-41.

  74. Kukidome D, Nishikawa T, Sonoda K, Imoto K, Fujisawa K, Yano M, et al. Activation of AMP-activated protein kinase reduces hyperglycemia induced mitochondrial reactive oxygen species production and promotes mitochondrial biogenesis in human umbilical vein endothelial cells. Diabetes. 2006; 55: 120-7.

  75. Haffner S, Temprosa M, Crandall J, Fowler S, Goldberg R, Horton E, et al. Intensive lifestyle intervention or metformin on inflammation and coagulation in participants with impaired glucose tolerance. Diabetes. 2005; 54: 1566-72.

  76. Thompson WG, Cook DA, Clark MM, Bardia A, Levine JA. Treatment of obesity. Mayo Clin Proc. 2007; 82: 93-101.

  77. Azain MJ. Role of fatty acids in adipocyte growth and development. J Anim Sci. 2004; 82: 916-24.

  78. Ludwig DS. The glycemic index: physiological mechanisms relating to obesity, diabetes, and cardiovascular disease. JAMA. 2002; 287: 2414-23.

  79. Mozaffarian D, Willett WC. Trans fatty acids and cardiovascular risk: A unique cardiometabolic imprint? Curr Atheroscler Rep. 2007; 9: 486-93.

  80. Berg AH, Combs TP, Du X, Brownlee M, Scherer PE. The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nat Med. 2001; 7: 947-53.

  81. Pischon T, Girman CJ, Rifai N, Hotamisligil GS, Rimm EB. Association between dietary factors and plasma adiponectin concentrations in men. Am J Clin Nutr. 2005; 81: 780-6.

  82. Wood RJ, Volek JS, Davis SR, Dell’Ova C, Fernandez ML. Effects of a carbohydrate-restricted diet on emerging plasma markers for cardiovascular disease. Nutr Metab. (Lond) 2006; 3: 19.

  83. Thompson PD, Buchner D, Pina IL, Balady GJ, Williams MA, Marcus BH, et al. Exercise and physical activity in the prevention and treatment of atherosclerotic cardiovascular disease: a statement from the Council on Clinical Cardiology (Subcommittee on Exercise, Rehabilitation, and Prevention) and the Council on Nutrition, Physical Activity, and Metabolism (Subcommittee on Physical Activity). Circulation. 2003; 107: 3109-16.

  84. Kelishadi R, Hashemi M, Mohammadifard N, Asgary S, Khavarian N. Association of changes in oxidative and proinflammatory states with changes in vascular function after a lifestyle modification trial among obese children. Clin Chem. 2008; 54: 147-53.

  85. Vincent HK, Bourguignon C, Vincent KR. Resistance training lowers exercise-induced oxidative stress and homocysteine levels in overweight and obese older adults. Obesity. (Silver Spring) 2006; 14: 1921-30.

  86. Selvin E, Paynter NP, Erlinger TP. The effect of weight loss on C-reactive protein: a systematic review. Arch Intern Med. 2007; 167: 31-9.

  87. Bobbert T, Rochlitz H, Wegewitz U, Akpulat S, Mai K, Weickert MO, et al. Changes of adiponectin oligomer composition by moderate weight reduction. Diabetes. 2005; 54: 2712-9.

  88. Dandona P, Mohanty P, Ghanim H, Aljada A, Browne R, Hamouda W, et al. The suppressive effect of dietary restriction and weight loss in the obese on the generation of reactive oxygen species by leukocytes, lipid peroxidation, and protein carbonylation. J Clin Endocrinol Metab. 2001; 86: 355-62.

  89. Noma K, Goto C, Nishioka K, Hara K, Kimura M, Umemura T, et al. Smoking, endothelial function, and Rho-kinase in humans. Arterioscler Thromb Vasc Biol. 2005; 25: 2630-5.

  90. Facchini FS, Hollenbeck CB, Jeppesen J, Chen YD, Reaven GM. Insulin resistance and cigarette smoking. Lancet. 1992; 339: 1128-30.

  91. Spector TD, Blake DR. Effect of cigarette smoking on Langerhans’ cells. Lancet. 1988; 2: 1028.

  92. Canoy D, Wareham N, Luben R, Welch A, Bingham S, Day N, Khaw KT. Cigarette smoking and fat distribution in 21,828 Br men and women: a population-based study. Obes Res. 2005; 13: 1466-75.

  93. Willi C, Bodenmann P, Ghali WA, Faris PD, Cornuz J. Active smoking and the risk of type diabetes: a systematic review and meta-analysis. JAMA. 2007; 298: 2654-64.

  94. Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002; 346: 393-403.

  95. Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H, Ilanne-Parikka P, et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. 2001; 344: 1343-50.




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