Obesity-associated insulin resistance is correlated to adipose tissue vascular endothelial growth factors and metalloproteinase levels

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• 作者：Francisco José Tinahones (1) (2) (3)
  Leticia Coín-Aragüez (1) (2)
  Maria Dolores Mayas (1) (2)
  Eduardo Garcia-Fuentes (1) (2)
  Carmen Hurtado-del-Pozo (4)
  Joan Vendrell (5)
  Fernando Cardona (1) (3)
  Rosa-Maria Calvo (4)
  Maria-Jesus Obregon (4)
  Rajaa El Bekay (1) (2)
  
• 关键词：Vascular Endothelial Growth Factor and Metalloproteinase ; Obesity ; Insulin Resistance ; Omentum Adipose Tissue ; Subcutaneous Adipose Tissue
• 刊名：BMC Physiology
• 出版年：2012
• 出版时间：December 2012
• 年：2012
• 卷：12
• 期：1
• 全文大小：540KB
• 参考文献：1. Bjorntorp P: Metabolic implications of body fat distribution. / Diabetes Care 1991, 14:1132-143. CrossRef
  2. Reaven G: All obese individuals are not created equal: insulin resistance is the major determinant of cardiovascular disease in overweight/obese individuals. / Diab Vasc Dis Res 2005, 2:105-12. CrossRef
  3. Colquitt JL, Picot J, Loveman E, Clegg AJ: Surgery for obesity. / Cochrane Database Syst Rev 2009, 2:CD003641.
  4. Macias-Gonzalez M, Moreno-Santos I, García-Almeida JM, Tinahones FJ, Garcia-Fuentes E: PPARgamma2 protects against obesity by means of a mechanism that mediates insulin resistance. / Eur J Clin Invest 2009,39(11):972-79. CrossRef
  5. Despres JP, Lemieux I: Abdominal obesity and metabolic syndrome. / Nature 2006, 444:881-87. CrossRef
  6. Blüher M: The distinction of metabolically 'healthy' from 'unhealthy' obese individuals. / Curr Opin Lipidol 2010,21(1):38-3. CrossRef
  7. Hanson RL, Imperatore G, Bennett PH, / et al.: Components of the 'metabolic syndrome' and incidence of type 2 diabetes. / Diabetes 2010, 51:3120-127. CrossRef
  8. Tan CY, Vidal-Puig A: Adipose tissue expandability: the metabolic problems of obesity may arise from the inability to become more obese. / Biochem Soc Trans 2008,36(Pt5):935-40. CrossRef
  9. Rocha VZ, Libby P: Obesity, inflammation, and atherosclerosis. / Nat Rev Cardiol 2009,6(6):399-09. CrossRef
  10. Karelis AD, St-Pierre DH, Conus F, / et al.: Metabolic and body composition factors in subgroups of obesity: what do we know? / J Clin Endocrinol Metab 2004,89(6):2569-575. CrossRef
  11. Soverini V, Moscatiello S, Villanova N, / et al.: Metabolic Syndrome and Insulin Resistance in Subjects with Morbid Obesity. / Obes Surg 2010,20(3):295-01. CrossRef
  12. Wildman RP, Muntner P, Reynolds K, / et al.: The Obese Without Cardiometabolic Risk Factor Clustering and the Normal Weight With Cardiometabolic Risk Factor Clustering Prevalence and Correlates of 2 Phenotypes Among the US Population (NHANES 1999-004). / Arch Intern Med 2008,168(15):1617-624. CrossRef
  13. Ledoux S, Queguiner I, Msika S, Calderari S, Rufat P, Gasc JM, Corvol P, Larger E: Angiogenesis associated with visceral and subcutaneous adipose tissue in severe human obesity. / Diabetes 2008,57(12):3247-257. CrossRef
  14. Christiaens V, Scroyen I, Lijnen HR: Role of proteolysis in development of murine adipose tissue. / Thromb Haemost 2008,99(2):290-94.
  15. Hausman GJ, Richardson RL: Adipose tissue angiogenesis. / J Anim Sci 2004,82(3):925-34.
  16. Carmeliet P, Ferreira V, Breier G, Pollefeyt S, Kieckens L, Gertsenstein M: Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. / Nature 1996, 380:435-39. CrossRef
  17. Olofsson B, Korpelainen E, Pepper MS, Mandriota SJ, Aase K, Kumar V: Vascular endothelial growth factor B (VEGF-B) binds to VEGF receptor-1 and regulates plasminogen activator activity in endothelial cells. / Proc Natl Acad Sci USA 1998, 95:11709-1714. CrossRef
  18. Joukov V, Pajusola K, Kaipainen A, Chilov D, Lahtinen I, Kukk E: A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases. / EMBO J 1996, 15:290-98.
  19. Karkkainen MJ, Haiko P, Sainio K, Partanen J, Taipale J, Petrova T: V: Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins. / Nat Immunol 2004, 5:74-0. CrossRef
  20. Stacker SA, Caesar C, Baldwin ME, Thornton GE, Williams RA, Prevo R: VEGF-D promotes the metastatic spread of tumor cells via the lymphatics. / Nat Med 2001, 7:186-91. CrossRef
  21. Spiegelman BM, Flier JS: Obesity and the regulation of energy balance. / Cell 2001,104(4):531-43. CrossRef
  22. Ailhaud G, Grimaldi P, Négrel R: Cellular and molecular aspects of adipose tissue development. / Annu Rev Nutr 1992, 12:207-33. CrossRef
  23. Crandall DL, Hausman GJ, Kral JG: A review of the microcirculation of adipose tissue: anatomic, metabolic, and angiogenic perspectives. / Microcirculation 1997, 4:211-32. CrossRef
  24. Vu TH, Werb Z: Matrix metalloproteinases: effectors of development and normal physiology. / Genes Dev 2000,14(17):2123-133. CrossRef
  25. Sternlicht MD, Werb Z: How matrix metalloproteinases regulate cell behavior. / Annu Rev Cell Dev Biol 2001, 17:463-16. CrossRef
  26. Zhang QX, Magovern CJ, Mack CA, Budenbender KT, Ko W, / et al.: Vascular endothelial growth factor is the major angiogenic factor in omentum: mechanism of the omentum-mediated angiogenesis. / J Surg Res 1997,67(2):147-54. CrossRef
  27. Voros G, Maquoi E, Demeulemeester D, Clerx N, Collen D, Lijnen HR: Modulation of angiogenesis during adipose tissue development in murine models of obesity. / Endocrinology 2005, 146:4545-554. CrossRef
  28. Kim JY, van de Wall E, Laplante M, Azzara A, Trujillo ME, / et al.: Obesity-associated improvements in metabolic profile through expansion of adipose tissue. / J Clin Invest 2007, 117:2621-637. CrossRef
  29. Zelzer E, Levy Y, Kahana C, Shilo BZ, Rubinstein M, Cohen B: Insulin induces transcription of target genes through the hypoxia-inducible factor HIF-1alpha/ARNT. / EMBO J 1998, 17:5085-094. CrossRef
  30. de Luca C, Olefsky JM: Inflammation and insulin resistance. / FEBS Lett 2008, 582:97-05. CrossRef
  31. Boden G: Obesity and free fatty acids. / Endocrinol Metab Clin North Am 2008, 37:635-46. CrossRef
  32. Roberts CK, Won D, Pruthi S, Kurtovic S, Sindhu RK, / et al.: Effect of a short-term diet and exercise intervention on oxidative stress, inflammation, MMP-9, and monocyte chemotactic activity in men with metabolic syndrome factors. / J Appl Physiol 2006, 100:1657-665. CrossRef
  33. Unal R, Yao-Borengasser A, Varma V, Rasouli N, Labbate C, / et al.: Matrix metalloproteinase-9 is increased in obese subjects and decreases in response to pioglitazone. / J Clin Endocrinol Metab 2010, 95:2993-001. CrossRef
  34. Bouloumie A, Sengenes C, Portolan G, Galitzky J, Lafontan M: Adipocyte produces matrix metalloproteinases 2 and 9: involvement in adipose differentiation. / Diabetes 2001, 50:2080-086. CrossRef
  35. Derosa G, Ferrari I, D'Angelo A, Tinelli C, Salvadeo SA, Ciccarelli L, Piccinni MN, Gravina A, Ramondetti F, Maffioli P, Cicero AF: Matrix metalloproteinase-2 and -9 levels in obese patients. / Endothelium 2008,15(4):219-24. CrossRef
  
• 作者单位：Francisco José Tinahones (1) (2) (3)
  Leticia Coín-Aragüez (1) (2)
  Maria Dolores Mayas (1) (2)
  Eduardo Garcia-Fuentes (1) (2)
  Carmen Hurtado-del-Pozo (4)
  Joan Vendrell (5)
  Fernando Cardona (1) (3)
  Rosa-Maria Calvo (4)
  Maria-Jesus Obregon (4)
  Rajaa El Bekay (1) (2)
  
  1. CIBER Fisiopatología Obesidad y Nutrición (CB06/03), Instituto de Salud Carlos III, Madrid, Spain
  2. Laboratorio de Investigación Biomédica, Hospital Clínico Universitario Virgen de la Victoria, Campus de Teatinos s/n, 29010, Málaga, Spain
  3. Servicio de Endocrinología, Hospital Virgen de la Victoria, Malaga, Spain
  4. Instituto de Investigaciones Biomedicas (IIBM, CSIC-UAM]), Madrid, Spain
  5. CIBERDEM. University Hospital of Tarragona Joan XXIII. IISPV, Rovira i Virgili University, Tarragona, Spain
  

文摘

Background The expansion of adipose tissue is linked to the development of its vasculature, which appears to have the potential to regulate the onset of obesity. However, at present, there are no studies highlighting the relationship between human adipose tissue angiogenesis and obesity-associated insulin resistance (IR). Results Our aim was to analyze and compare angiogenic factor expression levels in both subcutaneous (SC) and omentum (OM) adipose tissues from morbidly obese patients (n = 26) with low (OB/L-IR) (healthy obese) and high (OB/H-IR) degrees of IR, and lean controls (n = 17). Another objective was to examine angiogenic factor correlations with obesity and IR. Here we found that VEGF-A was the isoform with higher expression in both OM and SC adipose tissues, and was up-regulated 3-fold, together with MMP9 in OB/L-IR as compared to leans. This up-regulation decreased by 23% in OB/-H-IR compared to OB/L-IR. On the contrary, VEGF-B, VEGF-C and VEGF-D, together with MMP15 was down-regulated in both OB/H-IR and OB/L-IR compared to lean patients. Moreover, MMP9 correlated positively and VEGF-C, VEGF-D and MMP15 correlated negatively with HOMA-IR, in both SC and OM. Conclusion We hereby propose that the alteration in MMP15, VEGF-B, VEGF-C and VEGF-D gene expression may be caused by one of the relevant adipose tissue processes related to the development of IR, and the up-regulation of VEGF-A in adipose tissue could have a relationship with the prevention of this pathology.