Gelatinase B (MMP-9) deficiency does not affect murine adipose tissue development

 

PDF Download Buy Article Permissions and Reprints

Summary

This study was performed to follow up on the observation that gelatinase A (MMP-2) deficiency impairs adipose tissue development in mice. The aim was to evaluate the role of its functional homologue gelatinase B (MMP-9) in adipose tissue growth. MMP-9 antigen levels were determined in lean and in obese women before and after weight loss. MMP-9-deficient mice and wild-type littermates (genetic background 50% 129sv : 50% CDI or 99.975% C57Bl/6, ten generations backcrossed into C57Bl/6 background) were kept on a high-fat diet (HFD) for 15 weeks. Subcutaneous and gonadal fat pads were analysed in terms of weight and size/density of adipocytes and blood vessels. Obese women had higher MMP-9 serum levels than lean controls (383 ± 29 vs. 304 ± 27 ng/ml, p = 0.02); after weight reduction MMP-9 levels dropped to 334 ± 17 ng/ml (p = 0.1 vs. obese). However, MMP-9-deficient and littermate wild-type mice kept on HFD were indistinguishable in terms of body and fat weight. No effect of MMP-9 deficiency was observed on size or density of adipocytes or blood vessels in subcutaneous or gonadal fat depots. Similar observations were made when mice were kept on normal chow. In conclusion, in lean and obese women, body mass index correlates positively with MMP-9 serum levels (p < 0.0001). However, MMP-9 does not seem to play a major role in adipose tissue development in murine models of diet-induced obesity.

• References

• 1 Landolfi R, Rocca B, Patrono C. Bleeding and thrombosis in myeloproliferative disorders: mechanisms and treatment. Critical Rev Oncol Hematol 1995; 20: 203-222.
  CrossrefPubMedGoogle Scholar
• 2 Falanga A, Marchetti M, Vignoli A. et al. Leukocyte-platelet interaction in patients with essential thrombocythemia and polycythemia vera. Exp Hematol 2005; 33: 523-530.
  CrossrefPubMedGoogle Scholar
• 3 Falanga A, Marchetti M, Vignoli A. et al. V617F JAK-2 mutation in patients with essential thrombocythemia: relation to platelet, granulocyte, and plasma hemostatic and inflammatory molecules. Exp Hematol 2007; 35: 702-711.
  CrossrefPubMedGoogle Scholar
• 4 Falanga A, Marchetti M, Barbui T. et al. Pathogenesis of thrombosis in essential thrombocythemia and polycythemia vera: the role of neutrophils. Sem Hematol 2005; 42: 239-247.
  CrossrefPubMedGoogle Scholar
• 5 Elliott MA, Tefferi A. Thrombosis and haemorrhage in polycythaemia vera and essential thrombocythaemia. Br J Haematol 2005; 128: 275-290.
  CrossrefPubMedGoogle Scholar
• 6 Cines DB, Pollak ES, Buck CA. et al. Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood 1998; 91: 3527-3561.
  PubMedGoogle Scholar
• 7 Falanga A, Marchetti M, Evangelista V. et al. Polymorphonuclear leukocyte activation and hemostasis in patients with essential thrombocythemia and poly-cythemia vera. Blood 2000; 96: 4261-4266.
  PubMedGoogle Scholar
• 8 Freedman JE, Loscalzo J. et al. Nitric oxide and its relationship to thrombotic disorders. J Thromb Haemost 2003; Jun 01 (06) 1183-8 9.
  CrossrefPubMedGoogle Scholar
• 9 Carlos TM, Harlan JM. Leukocyte-endothelial adhesion molecules. Blood 1994; 84: 2068-2101.
  PubMedGoogle Scholar
• 10 Gearing AJ, Newman W. Circulating adhesion molecules in disease. Immunol Today 1993; 14: 506-512.
  CrossrefPubMedGoogle Scholar
• 11 Cella G, Bellotto F, Tona F. et al. Plasma markers of endothelial dysfunction in pulmonary hypertension. Chest 2001; 120: 1226-1230.
  CrossrefPubMedGoogle Scholar
• 12 Krieglstein CF, Granger DN. Adhesion molecules and their role in vascular disease. Am J Hypertens 2001; 14: 44S-54S.
  CrossrefPubMedGoogle Scholar
• 13 Blann AD, Tse W, Maxwell SJ. et al. Increased levels of the soluble adhesion molecule E-selectin in essential hypertension. J Hypertens 1994; 12: 925-928.
  PubMedGoogle Scholar
• 14 Patel C, Ghanim H, Ravishankar S. et al Prolonged reactive oxygen species generation and nuclear factor-kappaB activation after a high-fat, high-carbohydrate meal in the obese. J Clin Endocrinol Metab 2007; 92: 4476-4479.
  CrossrefPubMedGoogle Scholar
• 15 Ghanim H, Aljada A, Hofmeyer D. et al Circulating mononuclear cells in the obese are in a proinflammatory state. Circulation 2004; 110: 1564-1571.
  CrossrefPubMedGoogle Scholar
• 16 Glowinska-Olszewska B, Urban M. Elevated matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 in obese children and adolescents. Metabolism 2007; 56: 799-805.
  CrossrefPubMedGoogle Scholar
• 17 Glowinska-Olszewska B, Urban M, Florys B. Selected matrix metalloproteinases (MMP-2, MMP-9) in obese children and adolescents. Endokrynol Diabetol Chor Przemiany Materii Wieku Rozw 2006; 12: 179-183.
  PubMedGoogle Scholar
• 18 Vu TH, Shipley JM, Bergers G. et al MMP-9/gelatinase B is a key regulator of growth plate angiogenesis and apoptosis of hypertrophic chondrocytes. Cell 1998; 93: 411-422.
  CrossrefPubMedGoogle Scholar
• 19 Dubois B, Masure S, Hurtenbach U. et al Resistance of young gelatinase B-deficient mice to experimental autoimmune encephalomyelitis and necrotizing tail lesions. J Clin Invest 1999; 104: 1507-1515.
  CrossrefPubMedGoogle Scholar
• 20 Giles AR. Guidelines for the use of animals in biomedical research. Thromb Haemost 1987; 58: 1078-1084.
  Article in Thieme ConnectPubMedGoogle Scholar
• 21 Sjostrom L, Bjorntorp P, Vrana J. Microscopic fat cell size measurements on frozen-cut adipose tissue in comparison with automatic determinations of osmium-fixed fat cells. J Lipid Res 1971; 12: 521-530.
  PubMedGoogle Scholar
• 22 Laitinen L. Griffonia simplicifolia lectins bind specifically to endothelial cells and some epithelial cells in mouse tissues. Histochem J 1987; 19: 225-234.
  CrossrefPubMedGoogle Scholar
• 23 Alexander CM, Werb Z. Targeted disruption of the tissue inhibitor of metalloproteinases gene increases the invasive behavior of primitive mesenchymal cells derived from embryonic stem cells in vitro. J Cell Biol 1992; 118: 727-739.
  CrossrefPubMedGoogle Scholar
• 24 Kleiner DE, Stetler-Stevenson WG. Quantitative zymography: detection of picogram quantities of gelatinases. Anal Biochem 1994; 218: 325-329.
  CrossrefPubMedGoogle Scholar
• 25 World Health Organization. Obesity and overweight: Fact sheet N°311. Available at. http://www.who.int/mediacentre/factsheets/fs311/en/index.html Accessed: 26 October, 2009.
  PubMedGoogle Scholar
• 26 Maquoi E, Demeulemeester D, Voros G. et al Enhanced nutritionally induced adipose tissue development in mice with stromelysin-1 gene inactivation. Thromb Haemost 2003; 89: 696-704.
  Article in Thieme ConnectPubMedGoogle Scholar
• 27 Lijnen HR, Van Hoef B, Frederix L. et al Adipocyte hypertrophy in stromelysin-3 deficient mice with nutritionally induced obesity. Thromb Haemost 2002; 87: 530-535.
  Article in Thieme ConnectPubMedGoogle Scholar
• 28 Pendas AM, Folgueras AR, Llano E. et al Diet-induced obesity and reduced skin cancer susceptibility in matrix metalloproteinase 19-deficient mice. Mol Cell Biol 2004; 24: 5304-5313.
  CrossrefPubMedGoogle Scholar
• 29 Lijnen HR, Demeulemeester D, Van Hoef B. et al Deficiency of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) impairs nutritionally induced obesity in mice. Thromb Haemost 2003; 89: 249-255.
  Article in Thieme ConnectPubMedGoogle Scholar
• 30 Chun TH, Hotary KB, Sabeh F. et al A pericellular collagenase directs the 3-di-mensional development of white adipose tissue. Cell 2006; 125: 577-591.
  CrossrefPubMedGoogle Scholar
• 31 West DB, Boozer CN, Moody DL. et al Dietary obesity in nine inbred mouse strains. Am J Physiol 1992; 262: R1025-1032.
  PubMedGoogle Scholar
• 32 Bisoendial RJ, Birjmohun RS, Akdim F. et al C-reactive protein elicits white blood cell activation in humans. Am J Med 2009; 122 582 e1-9.
  CrossrefPubMedGoogle Scholar
• 33 Kolaczkowska E, Grzybek W, van Rooijen N. et al Neutrophil elastase activity compensates for a genetic lack of matrix metalloproteinase-9 (MMP-9) in leukocyte infiltration in a model of experimental peritonitis. J Leukoc Biol 2009; 85: 374-381.
  CrossrefPubMedGoogle Scholar