Blancas-Flores G, Almanza-Pérez JC, López-Roa RI, Alarcón-Aguilar FJ, García-Macedo R, Cruz M

Idioma: Español
Referencias bibliográficas: 45
Paginas: 88-97
Archivo PDF: 219.13 Kb.

RESUMEN

La obesidad es un problema muy importante a nivel mundial que ha aumentado rápidamente, alcanzando características de pandemia. En los últimos años se ha observado que los pacientes obesos presentan un estado inflamatorio crónico de bajo grado como una consecuencia del incremento en la masa del tejido adiposo, que lleva a un aumento en la producción de mediadores proinflamatorios que son conjuntamente estimulados por señales de origen exógeno y/o endógeno. El tejido adiposo contiene fibroblastos, preadipocitos, adipocitos y macrófagos; estos últimos contribuyen de manera importante al proceso inflamatorio sistémico con la producción de mediadores proinflamatorios. Así, existe una asociación íntima, altamente coordinada, entre las vías inflamatorias y las metabólicas; destaca la coincidencia en las funciones de los macrófagos y los adipocitos en la obesidad. Dilucidar los vínculos que existen entre obesidad e inflamación es de importancia capital dentro del campo de la biología molecular; esto implica el reconocimiento de las adipocinas, moléculas sintetizadas por los adipocitos, para dar lugar al descubrimiento de nuevos blancos terapéuticos relacionados con la inmunidad y el metabolismo, y de esta manera abrir la posibilidad de frenar la evolución de los procesos inflamatorios que culminan en enfermedades degenerativas.

REFERENCIAS (EN ESTE ARTÍCULO)

1. Pi-Sunyer FX. The obesity epidemic: pathophysiology and consequences of obesity. Obes Res 2002;10:97S-104S.

2. Mendivil ACO, Sierra AID. Avances en obesidad. Rev Fac Med Univ Nac Colombia 2004;52:270-286.

3. Palou A, Bonet ML, Picó C, Rodríguez AM. Nutrigenómica y obesidad. Rev Med Univ Navarra 2004;48:36-48.

4. Díaz M. Presente y futuro del tratamiento farmacológico de la obesidad. Rev Argent Cardiol 2005;73:137-144.

5. Berg AH, Scherer PE. Adipose tissue, inflammation, and cardiovascular disease. Circ Res 2005;96:939-949.

6. Lau DCW, Dhillon B, Yan H, Szmitko PE, Verma S. Adipokines: molecular links between obesity and atherosclerosis. Am J Physiol Heart Circ Physiol 2005;288:H2031-H2041.

7. Fantuzzi G. Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol 2005;115:911-919.

8. Yudkin JS. Adipose tissue, insulin action and vascular disease: inflammatory signals. Int J Obes 2003;27:S25-S28.

9. Khovidhunkit W, Kim MS, Memon RA, Shigenaga JK, Moser AH, Feingold KR, et al. Effects of infection and inflammation on lipid and lipoprotein metabolism: mechanisms and consequences to the host. J Lipid Res 2004;45:1169–1196.

10. Wellen KE, Hotamisligil GS. Inflammation, stress, and diabetes. J Clin Inv 2005;115:1111-1119.

11. Medzhitov R, Janeway CA Jr. An ancient system of host defense. Curr Opin Immunol 1998;10:12-15.

12. Pickup JC. Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes. Diabetes Care 2004;27:813–823.

13. Lemaitre B, Nicolas E, Michaut L, Reichhart JM, Hoffmann JA. The dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell 1996;86:973-983.

14. Barton GM, Medzhitov R. Toll-like receptor signaling pathways. Science 2003;300:1524-1525.

15. Murakami K, Bujo H, Unoki H, Saito Y. High fat intake induces a population of adipocytes to co-express TLR2 and TNF-alpha in mice with insulin resistance. Biochem Biophys Res Commun 2007;354:727-734.

16. Vitseva OI, Tanriverdi K, Tchkonia TT, Kirkland JL, McDonnell ME, Apovian CM, et al. Inducible Toll-like receptor and NF-kappaB regulatory pathway expression in human adipose tissue. Obesity (Silver Spring) 2008;16:932-937.

17. Creely SJ, McTernan PG, Kusminski CM, Fisher M, Da Silva NF, Khanolkar M, et al. Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes. Am J Physiol Endocrinol Metab 2007;292:E740-E747.

18. Cai D, Yuan M, Frantz DF, Melendez PA, Hansen L, Lee J, et al. Local and systemic insulin resistance resulting from hepatic activation of IKKb and NF-kB. Nat Med 2005;11:183-190.

19. Arkan MC, Hevener AL, Greten FR, Maeda S, Li ZW, Long JM, et al. IKK-beta links inflammation to obesity-induced insulin resistance. Nat Med 2005;11:191-198.

20. Cornell RP, McClellan CC. Modulation of hepatic reticuloendothelial system phagocytosis by pancreatic hormones. J Reticuloendothel Soc 1982;32:397-407.

21. Cornell RP. Endogenous gut-derived bacterial endotoxin tonically primes pancreatic secretion of insulin in normal rats. Diabetes 1985;34:1253-1259.

22. Sánchez RP, Sanz JM, Martín AP, Martín ER, Mon Soto MA, García MS. Balance entre citocinas pro y antiinflamatorias en estados sépticos. Med Intensiva 2005;29:151-158.

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

24. Yamagishi S, Nakamura K, Jinnouchi Y, Takenaka K, Imaizumi T. Molecular mechanisms for vascular injury in the metabolic syndrome. Drugs Exp Clin Res 2005;31:123-129.

25. Nicoletti G, Giugliano G, Pontillo A, Cioffi M, D’Andrea F, Giugliano D, et al. Effect of a multidisciplinary program of weight reduction on endothelial function in obese women. J Endocrinol Invest 2003;26:RC5-RC8.

26. Kopp HP, Kopp CW, Festa A, Krzyzanowska K, Kriwanek S, Minar E, et al. Impact of weight loss on inflammatory proteins and their association with the insulin resistance syndrome in morbidly obese patients. Arterioscler Thromb Vasc Biol 2003;23:1042-1047.

27. Charriere G, Cousin B, Arnaund E, André M, Bacou F, Pénicaud L, et al. Preadipocyte conversion to macrophage. Evidence of plasticity. J Biol Chem 2003;278:9850–9855.

28. Ouchi N, Kihara S, Funahashi T, Nakamura T, Nishida M, Kumada M, et al. Reciprocal association of C-reactive protein with adiponectin in blood stream and adipose tissue. Circulation 2003;107:671-674.

29. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leible RL, Ferrante AW Jr. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 2003;112:1796-1808.

30. Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 2003;112:1821-1830.

31. Kvasnicka T, Kvasnicka J, Ceska R, Grauova B, Vrablik M. Increasing plasma levels of soluble cell adhesion molecules (sE-Selectin, sP-Selectin and sICAM-1) in overweight adults with combined hyperlipidemia. Sb Lek 2001;102:473-477.

32. Gerhardt CC, Romero IA, Cancello R, Camoin L, Strosberg AD. Chemokines control fat accumulation and leptin secretion by cultured human adipocytes. Mol Cell Endocrinol 2001;175:81-92.

33. Bruun JM, Lihn AS, Madan AK, Pedersen SB, Schiott KM, Fain JN, et al. Higher production of interleukin-8 in visceral compared to subcutaneous adipose tissue: implications of non-adipose cells in adipose tissue. Am J Physiol Endocrinol Metab 2004;286:E8-E13.

34. Nakatani Y, Kaneto H, Kawamori D, Yoshiuchi K, Hatazaki M, Matsuoka T, et al. Involvement of endoplasmic reticulum stress in insulin resistance and diabetes. J Biol Chem 2005;280:847-851.

35. Trayhurn P, Wood IS. Adipokines: inflammation and the pleotropic role of white adipose tissue. Br J Nutr 2004;92:347-355.

36. Lowell BB, Shulman GI. Mitochondrial dysfunction and type 2 diabetes. Science 2005;307:384-387.

37. Lin Y, Chen Y, Cline GW, Zhang D, Zong H, Wang Y, et al. The hyperglycemia-induced inflammatory response in adipocytes: the role of reactive oxygen species. J Biol Chem 2005;280:4617-4626.

38. Saltiel AR, Kahn CR. Insulin signalling and the regulation of glucose and lipid metabolism. Nature 2001;414:799-806.

39. Hotamisligil GS, Budavari A, Murray D, Spiegelman BM. Reduced tyrosine kinase activity of the insulin receptor in obesity-diabetes. Central role of tumor necrosis factor-a. J Clin Invest 1994;94:1543-1549.

40. Perseghin G, Petersen K, Shulman GI. Cellular mechanism of insulin resistance: potential links with inflammation. Int J Obes Relat Metab Disord 2003;27:S6-S11.

41. Lolmede K, Durant de Saintfront V, Galizky J, Lanfontan M, Bouloumie A. Effects of hypoxia on the expression of proangiogenic factors in differentiated 3T3-F442A adipocytes. Int J Obes 2003;27:1187-1195.

42. Höpfl G, Ogunshola O, Gassmann M. HIFs and tumors. Causes and consequences. Am J Physiol Regul Integr Comp Physiol 2004;286:R608-R623.

43. Almanza-Pérez JC, Blancas-Flores G, García-Macedo R, Alarcón-Aguilar FJ, Cruz M. Leptina y su relación con la obesidad y la diabetes mellitus tipo 2. Gac Méd Méx 2008;144:535-542.

44. Alarcon-Aguilar FJ, Almanza-Perez J, Blancas G, Angeles S, Garcia-Macedo R, Roman R, Cruz M. Glycine regulates the production of pro-inflammatory cytokines in lean and monosodium glutamate-obese mice. Eur J Pharmacol 2008;599:152-158.

45. García-Macedo R, Sanchez-Muñoz F, Almanza-Perez JC, Duran-Reyes G, Alarcon-Aguilar F, Cruz M. Glycine increases mRNA adiponectin and diminishes pro-inflammatory adipokines expression in 3T3-L1 cells. Eur J Pharmacol 2008;587:317-321.