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

Matthias Van Hul; Heléne Piccard; H. Roger Lijnen

doi:10.1160/TH09-10-0739

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2010; 104(01): 165-171
DOI: 10.1160/TH09-10-0739

Animal Models

Schattauer GmbH

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

Authors

Matthias Van Hul

¹Center for Molecular and Vascular Biology, University Leuven, Leuven, Belgium
Heléne Piccard

²Laboratory of Immunobiology, Rega Institute for Medical Research, University Leuven, Leuven, Belgium
H. Roger Lijnen

¹Center for Molecular and Vascular Biology, University Leuven, Leuven, Belgium

Abstract

PDF Download

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.

Keywords

Obesity - adipose tissue - MMPs - gelatinase

PDF (181 kb)

References

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.
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.
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.
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.
5 Elliott MA, Tefferi A. Thrombosis and haemorrhage in polycythaemia vera and essential thrombocythaemia. Br J Haematol 2005; 128: 275-290.
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.
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.
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.
9 Carlos TM, Harlan JM. Leukocyte-endothelial adhesion molecules. Blood 1994; 84: 2068-2101.
10 Gearing AJ, Newman W. Circulating adhesion molecules in disease. Immunol Today 1993; 14: 506-512.
11 Cella G, Bellotto F, Tona F. et al. Plasma markers of endothelial dysfunction in pulmonary hypertension. Chest 2001; 120: 1226-1230.
12 Krieglstein CF, Granger DN. Adhesion molecules and their role in vascular disease. Am J Hypertens 2001; 14: 44S-54S.
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.
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.
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.
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.
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.
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.
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.
20 Giles AR. Guidelines for the use of animals in biomedical research. Thromb Haemost 1987; 58: 1078-1084.
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.
22 Laitinen L. Griffonia simplicifolia lectins bind specifically to endothelial cells and some epithelial cells in mouse tissues. Histochem J 1987; 19: 225-234.
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.
24 Kleiner DE, Stetler-Stevenson WG. Quantitative zymography: detection of picogram quantities of gelatinases. Anal Biochem 1994; 218: 325-329.
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.
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.
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.
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.
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.
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.
31 West DB, Boozer CN, Moody DL. et al Dietary obesity in nine inbred mouse strains. Am J Physiol 1992; 262: R1025-1032.
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.
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.