Las adipocitoquinas en la génesis y evolución del Síndrome metabólico

Sergio Santana Porbén

Texto completo:

PDF

Resumen

La visión clásica del tejido adiposo como un almacén pasivo de triglicéridos ha cambiado drásticamente en años recientes luego de la identificación de las adipocitoquinas: proteínas sintetizadas por el adipocito y liberadas a la circulación sanguínea, que pueden influir sobre la homeostasis de la energía metabólica y la respuesta de las células/tejidos/ órganos de la economía a la acción de la insulina. Mientras algunas de las adipoquinas incrementan la sensibilidad tisular a la estimulación de la insulina, y con ello, la utilización de glúcidos y triglicéridos, otras hacen a la célula periférica resistente a la influencia de esta hormona pancreática, lo que resulta en hiperglicemia e hiper-trigliceridemia. La transición entre un estado insulino-permisivo y otro insulino-resistivo depende del tamaño y la distribución topográfica del tejido adiposo. Un mejor entendimiento de la estructura, propiedades y funciones de las Adipocitoquinas pudiera resultar en una superior comprensión de la génesis y evolución del Síndrome metabólico asociado a la Obesidad, y con ello, en nuevas terapias farmacológicas para el tratamiento de las complicaciones del mismo. No obstante, se ha revelado que la reducción de la grasa corporal, y la redistribución de la misma, resultan en cambios notables de la producción y la actividad de las adipocitoquinas. Se insiste entonces en la reeducación del sujeto obeso sobre la necesidad de la modificación de hábitos y estilos de vida que traigan consigo la prevención de la aparición de las formas clínicas del Síndrome metabólico.

Palabras clave

Adipocitoquinas; Obesidad; Síndrome metabólico; Tejido adiposo

Referencias

Kahn R, Buse J, Ferrannini E, Stern M. The metabolic syndrome: time for a critical appraisal. Joint statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia 2005;48:1684-99.

Seidell JC, Bouchard C. Visceral fat in relation to health: is it a major culprit or simply an innocent bystander? Int J Obes Relat Metab Disord 1997;21:626-31.

Sethi JK, Vidal Puig A. Visfatin: the missing link between intra-abdominal obesity and diabetes? Trends in Molecular Medicine 2005;11:344-47.

Shapiro B, Wertheimer E. The metabolic activity of adipose tissue a review. Metabolism 1956;5:79-86.

Frayn KN. Macronutrient metabolism of adipose tissue at rest and during exercise: A methodological viewpoint. Proc Nutr Soc 1999;58:877-86.

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.

Fonseca Alaniz MH, Takada J, Alonso Vale MI, Lima FB. Adipose tissue as an endocrine organ: from theory to practice. J Pediatr (Rio J) 2007;83(5 Suppl):S192-S203.

Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alfa: Direct role in obesity-linked insulin resistance. Science 1993;259:87-91.

Matsuzawa Y. Adipocytokines and metabolic syndrome. Semin Vasc Med 2005;5:34-9.

Staiger H, Haring HU. Adipocytokines: Fat-derived humoral mediators of metabolic homeostasis. Exp Clin Endocrinol Diabetes 2005;113:67-79.

Cannon B, Nedergaard J. Brown adipose tissue: Function and physiological significance. Physiol Rev 2004;84:277-359.

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.

Tartaglia LA, Dembski M, Weng X, Deng N, Culpepper J, Devos R, Richards GJ y cols. Identification and expression cloning of a leptin receptor, OB-R. Cell 1995;83:1263-71.

Rohner-Jeanrenaud F, Jeanrenaud B. The discovery of leptin and its impact in the understanding of obesity. Eur J Endocrinol 1996;135:649-50.

Ostlund RE Jr, Yang JW, Klein S, Gingerich R. Relation between plasma leptin concentration and body fat, gender, diet, age, and metabolic covariates. J Clin Endocrinol Metab 1996;81:3909-13.

Frühbeck G. A heliocentric view of leptin. Proc Nutr Soc 2001;60:301-18.

Koh KK, Park SM, Quon MJ. Leptin and cardiovascular disease: response to therapeutic interventions. Circulation 2008;117:3238-49.

Heymsfield SB, Greenberg AS, Fujioka K, Dixon RM, Kushner R, Hunt T, Lubina JA, Patane J, Self B, Hunt P, McCamishM1999 Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. JAMA 282:1568-75.

Scherer PE, Williams S, Fogliano M, Baldini G, Lodish HF 1995 A novel serum protein similar to C1q, produced exclusively in adipocytes. J Biol Chem 270:26746-9.

Chow WS, Cheung BM, Tso AW, Xu A, Wat NM, Fong CH, Ong LH, Tam S, Tan KC, Janus ED, Lam TH, Lam KS. Hypoadiponectinemia as a predictor for the development of hypertension: a 5-year prospective study. Hypertension 2007;49:1455-61.

Wang Y, Lam KS, Yau MH, Xu. Post-translational modifications of adiponectin: mechanisms and functional implications. Biochem J 2008;409:623-33.

Kadowaki T, Yamauchi T 2005 Adiponectin and adiponectin receptors. Endocr Rev 2005;26:439-51.

Kadowaki T, Yamauchi T, Kubota N, Hara K, Ueki K, Tobe K. Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest 2006;116:1784-92.

Bodles AM, Banga A, Rasouli N, Ono F, Kern PA, Owens RJ. Pioglitazone increases secretion of high-molecular-weight adiponectin from adipocytes. Am J Physiol Endocrinol Metab 2006;291:E1100-E1105.

Kim JY, van de WE, Laplante M, Azzara A, Trujillo ME, Hofmann SM, Schraw T; et al. Obesity-associated improvements in metabolic profile through expansion of adipose tissue. J Clin Invest 2007;117:2621-37.

Maeda N, Shimomura I, Kishida K, Nishizawa H, Matsuda M, Nagaretani H, Furuyama N; et al. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nature Med 2002;8:731-7.

Zhu W, Cheng KKY, Vanhoutte PM, Lam KSL, Xu A. Vascular effects of adiponectin: molecular mechanisms and potential therapeutic intervention. Clin Sci (Lond) 2008;114:361-74.

Kadowaki T, Yamauchi T, Kubota N. The physiological and pathophysiological role of adiponectin and adiponectin receptors in the peripheral tissues and CNS. FEBS Lett 2008;582:74-80.

Berg AH, Scherer PE. Adipose tissue, inflammation, and cardiovascular disease. Circ Res 2005;96:939-49.

Fruebis J, Tsao TS, Javorschi S, Ebbets-Reed D, Erickson MR, Yen FT, Bihain BE, Lodish HF. Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. Proc Natl Acad Sci USA 2001;98:2005-10.

Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA. The hormone resistin links obesity to diabetes. Nature 2001;409:307-12.

Patel SD, Rajala MW, Rossetti L, Scherer PE, Shapiro L. Disulfide-dependent multimeric assembly of resistin family hormones. Science 2004;304:1154-8.

Ouchi N, Parker JL, Lugus JJ, Walsh K. Adipokines in inflammation and metabolic disease. Nature Rev Immunol 2011;11:85-97.

Steppan CM, Lazar MA. The current biology of resistin. J. Intern Med 2004;255:439-47.

Steppan CM, Brown EJ, Wright CM, Bhat S, Banerjee RR, Dai CY, Enders GH, Silberg DG, Wen X, Wu GD, LazarMA. A family of tissue-specific resistin-like molecules. Proc Natl Acad Sci USA 2001;98:502-6.

Samal B, Sun Y, Stearns G, Xie C, Suggs S, McNiece I. Cloning and characterization of the cDNA encoding a novel human pre-B-cell colony enhancing factor. Mol Cell Biol 1994;14:1431-7.

Berndt J, Kloting N, Kralisch S, Kovacs P, Fasshauer M, Schon MR, Stumvoll M, Bluher M. Plasma visfatin concentrations and fat depot-specific mRNA expression in humans. Diabetes 2005;54:2911-6.

Varma V, Yao-Borengasser A, Rasouli N, BodlesAM, Phanavanh B, Lee MJ, Starks T, Kern LM, Spencer III HJ, McGehee Jr RE, Fried SK, Kern PA. Human visfatin expression: relationship to insulin sensitivity, intramyocellular lipid and inflammation. J Clin Endocrinol Metab 2007;92:666-72.

Rasouli N, Kern PA. Adipocytokines and the metabolic complications of obesity. J Clin Endocrinol Metab 2008;93:S64-S73.

Yang RZ, Lee MJ, Hu H, Pray J, Wu HB, Hansen BC, Shuldiner AR, Fried SK, McLenithan JC, Gong DW. Identification of omentin as a novel depot-specific adipokine in human adipose tissue: Possible role in modulating insulin action. Am J Physiol Endocrinol Metab 2006;290:E1253-E1261.

de Souza Batista CM, Yang RZ, Lee MJ, Glynn NM, Yu DZ, Pray J y cols. Omentin plasma levels and gene expression are decreased in obesity. Diabetes 2007;56:1655-61.

Rosen ED Spiegelman BM. Adipocytes as regulators of energy balance and glucose homeostasis. Nature 2006;444:847-53.

Hida K, Wada J, Eguchi J, Zhang H, Baba M, Seida A; et al. Visceral adipose tissue-derived serine protease inhibitor: a unique insulin-sensitizing adipocytokine in obesity. Proc Natl Acad Sci USA 2005;102:10610-5.

Fukuhara A, Matsuda M, Nishizawa M, Segawa K, Tanaka M, Kishimoto K y cols. Visfatin: a protein secreted by visceral fat that mimics the effects of insulin. Science 2005;307:426-30.

Fukuhara A, Matsuda M, Nishizawa M, Segawa K, Tanaka M, Kishimoto K y cols. Retraction. Science 2007;318:565.

Antuna Puente B, Feve B, Fellahi S, Bastard JP. Adipokines: The missing link between insulin resistance and obesity. Diab Metab 2008;34:2-11

Pi-Sunyer X, Blackburn G, Brancati FL, Bray GA, Bright R, Clark JM y cols. Reduction in weight and cardiovascular disease risk factors in individuals with type 2 diabetes: one-year results of the look AHEAD trial. Diabetes Care 2007;30:1374-83.

Curat CA, Miranville A, Sengenes C, Dile M, Tonos C, Busse R y cols. From blood monocytes to adipose tissue-resident macrophages: Induction of diapedesis by human mature adipocytes. Diabetes 2004;53:1285-92.

Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of US adults. N Engl J Med 2003;348:1625-38.

Housa D, Housova J, Vernerova Z, Haluzik M. Adipocytokines and cancer. Physiol Res 2006;55:233-44.

van Kruijsdijk RCM, van der Wall E, Visseren FLJ. Obesity and cancer: The role of dysfunctional adipose tissue. Cancer Epidemiol Biomarkers Prev 2009;18:2569-78.

Masaki T, Yoshimatsu H. Obesity, Adipocytokines and Cancer. Transl Oncogenomics 2008;3:45-52.

Rokling-Andersen MH, Reseland JE, Veierod MB, Anderssen SA, Jacobs DR Jr, Urdal P; et al. Effects of long-term exercise and diet intervention on plasma adipokine concentrations. Am J Clin Nutr 2007;86:1293-1301.

Miller GD, Nicklas BJ, Davis CC, Ambrosius WT, Loeser RF, Messier SP. Is serum leptin related to physical function and is it modifiable through weight loss and exercise in older adults with knee osteoarthritis? Int J Obes Relat Metab Disord 2004;28:1383-90.

Nicklas BJ, Ambrosius W, Messier SP, Miller GD, Penninx BW, Loeser RF; et al. Diet-induced weight loss, exercise, and chronic inflammation in older, obese adults: A randomized controlled clinical trial. Am J Clin Nutr 2004;79:544-51.

Madsen EL, Rissanen A, Bruun JM, Skogstrand K, Tonstad S, Hougaard DM; et al. Weight loss larger than 10% is needed for general improvement of levels of circulating adiponectin and markers of inflammation in obese subjects: a 3-year weight loss study. Eur J Endocrinol 2008;158:179-87.

Kralisch S, Klein J, Bluher M, Paschke R, Stumvoll M, Fasshauer M. Therapeutic perspectives of adipocytokines. Expert Opin Pharmacother 2005;6:863-72.

Kobayashi K. Adipokines: therapeutic targets for metabolic syndrome. Curr Drug Targets 2005;6:525-9.

Pagotto U, Vanuzzo D, Vicennati V, Pasquali R. Pharmacological therapy of obesity. G Ital Cardiol (Rome) 2008;9(4 Suppl 1):83S-93S.

Carella AM, Conte M. Therapeutic options for metabolic syndrome in obese patients. Clin Ter 2007;158:457-64.

Padwal R, Li SK, Lau DC. Long-term pharmacotherapy for obesity and overweight. Cochrane Database Syst Rev 2004;3:CD004094.

Weinstock RS, Dai H, Wadden TA. Diet and exercise in the treatment of obesity: effects of 3 interventions on insulin resistance. Arch Intern Med 1998;158:2477-83.

Simpson KA, Singh MA: Effects of exercise on adiponectin: a systematic review. Obesity (Silver Spring) 2008;16:241-56.

Enlaces refback

  • No hay ningún enlace refback.


Bookmark and Share