Download PDF
Thromb Haemost 2003; 89(04): 696-704
DOI: 10.1055/s-0037-1613586
Cellular Proteolysis and Oncology
Schattauer GmbH

Enhanced nutritionally induced adipose tissue development in mice with stromelysin-1 gene inactivation

Erik Maquoi
1   Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium
,
Diego Demeulemeester
1   Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium
,
Gabor Vörös
1   Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium
,
Désire Collen
1   Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium
,
H. Roger Lijnen
1   Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium
› Author Affiliations Financial support: This study was supported financially by grants from the Interuniversity Attraction Poles (IUAP, project P5/02) and the Flemish Fund for Scientific Research (FWO, project G.0112.02).
Further Information

Publication History

Received 28 October 2002

Accepted after revision 12 January 2003

Publication Date:
07 December 2017 (online)

    Permissions and Reprints

Summary

To investigate a potential role of stromelysin-1 (MMP-3) in development of adipose tissue, 5 week old male MMP-3 deficient mice (MMP-3-/-) and wild-type (MMP-3+/+) controls were kept on a high fat diet (HFD) for 15 weeks. MMP-3-/- mice were hyperphagic and gained more weight than the MMP-3+/+ mice. At the time of sacrifice, the body weight of the MMP-3-/- mice was significantly higher than that of the MMP-3+/+ mice, as was the weight of the isolated subcutaneous (SC) and gonadal (GON) fat deposits. Significant adipocyte hypertrophy was observed in the GON but not in the SC adipose tissue of MMP-3-/- mice. Fasting plasma glucose and cholesterol levels were comparable in both genotypes, whereas triglyceride levels were significantly lower in MMP-3-/- mice. Staining with an endothelial cell specific lectin revealed a significantly higher blood vessel density and larger total stained area in the GON adipose tissues of MMP-3-/- mice. Thus, in a murine model of nutritionally induced obesity, MMP-3 impairs adipose tissue development, possibly by affecting food intake and/or adipose tissue-related angiogenesis.

Theme paper: Part of this paper was originally presented at the joint meetings of the 16th International Congress of the International Society of Fibrinolysis and Proteolysis (ISFP) and the 17th International Fibrinogen Workshop of the International Fibrinogen Research Society (IFRS) held in Munich, Germany, September, 2002.

Keywords

MMP-3 - stromelysin-1 - obesity - adipose tissue - adipocyte - angio-genesis
 

  • References

  • 1 Crandall DL, Hausman GJ, Kral JG. A review of the microcirculation of adipose tissue: anatomic, metabolic, and angiogenic perspectives. Microcirculation 1997; 4: 211-32.
    CrossrefPubMedGoogle Scholar
  • 2 Dollery CM, McEwan JR, Henney AM. Matrix metalloproteinases and cardiovascular disease. Circ Res 1995; 77: 863-8.
    CrossrefPubMedGoogle Scholar
  • 3 Carmeliet P, Collen D. Development and disease in proteinase-deficient mice: role of the plasminogen, matrix metalloproteinase and coagulation system. Thromb Res 1998; 91: 255-85.
    CrossrefPubMedGoogle Scholar
  • 4 Lijnen HR. Plasmin and matrix metalloproteinases in vascular remodeling. Thromb Haemost 2001; 86: 324-33.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 5 Brown LM, Fox HL, Hazen SA, LaNoue KF, Rannels SR, Lynch CJ. Role of the matrixin MMP-2 in multicellular organization of adipocytes cultured in basement membrane components. Am J Physiol 1997; 272: C937-49.
    CrossrefPubMedGoogle Scholar
  • 6 Lijnen HR, Maquoi E, Holvoet P, Mertens A, Lupu F, Morange P, Alessi MC, Juhan-Vague I. Adipose tissue expression of gelatinases in mouse models of obesity. Thromb Haemost 2001; 85: 1111-6.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 7 Bouloumié A, Sengenès C, Portolan G, Galitzky J, Lafontan M. Adipocyte produces matrix metalloproteinases 2 and 9. Involvement in adipocyte differentiation. Diabetes 2001; 50: 2080-6.
    CrossrefPubMedGoogle Scholar
  • 8 Nagase H. Activation mechanisms of matrix metalloproteinases. Biol Chem 1997; 378: 151-60.
    PubMedGoogle Scholar
  • 9 Sternlicht MD, Werb Z. How matrix metalloproteinases regulate cell behavior. Ann Rev Cell Dev Biol 2001; 17: 463-516.
    CrossrefPubMedGoogle Scholar
  • 10 Talhouk RS, Bissell MJ, Werb Z. Coordinated expression of extracellular matrix-degrading proteinases and their inhibitors regulates mammary epithelial function during involution. J Cell Biol 1992; 118: 1271-82.
    CrossrefPubMedGoogle Scholar
  • 11 Witty JP, Wright JH. Matrisian ML. Matrix metalloproteinases are expressed during ductal and alveolar mammary morphogenesis, and misregulation of stromelysin-1 in transgenic mice induces unscheduled alveolar development. Mol Biol Cell 1995; 6: 1287-1303.
    CrossrefPubMedGoogle Scholar
  • 12 Alexander CM, Selvarajan S, Mudgett J, Werb Z. Stromelysin-1 regulates adipogenesis during mammary gland involution. J Cell Biol 2001; 152: 693-703.
    CrossrefPubMedGoogle Scholar
  • 13 Maquoi E, Munaut C, Colige A, Collen D, Lijnen HR. Modulation of the expression of murine matrix metalloproteinases and their tissue inhibitors with obesity. Diabetes 2002; 51: 1093-101.
    CrossrefPubMedGoogle Scholar
  • 14 Mudgett JS, Hutchinson NI, Chartrain NA, Forsyth AJ, Mac Donnel J, Singer II, Bayne EK, Flanagan J, Kawka D, Shen CF, Stevens K, Chen H, Trumbauer M, Visco DM. Susceptibility of stromelysin-1 deficient mice to collagen-induced arthritis and cartilage destruction. Arthritis Rheum 1998; 41: 110-21.
    CrossrefPubMedGoogle Scholar
  • 15 Giles AR. Guidelines for the use of animals in biomedical research. Thromb Haemost 1987; 58: 1078-84.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 16 Declerck PJ, Verstreken M, Collen D. Immunoassay of murine t-PA, u-PA and PAI-1 using monoclonal antibodies raised in gene-inactivated mice. Thromb Haemost 1995; 74: 1305-9.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 17 Lijnen HR, Silence J, Van Hoef B, Collen D. Stromelysin-1 (MMP-3)-independent gelatinase expression and activation in mice. Blood 1998; 91: 2045-53.
    PubMedGoogle Scholar
  • 18 Galis ZS, Sukhova GK, Libby P. Microscopic localization of active proteases by in situ zymography: detection of matrix metalloproteinase activity in vascular tissue. FASEB J 1995; 9: 974-80.
    CrossrefPubMedGoogle Scholar
  • 19 Laitinen L. Griffonia simplicifolia lectins bind specifically to endothelial cells and some eptithelial cells in mouse tissues. Histochem J 1987; 19: 225-34.
    CrossrefPubMedGoogle Scholar
  • 20 Hoying JB, Boswell CA, Williams SK. Angiogenic potential of microvessel fragments established in three-dimensional collagen gels. In Vitro Cell Dev Biol 1996; 32: 409-19.
    CrossrefPubMedGoogle Scholar
  • 21 Carter WB, Crowell SL, Boswell CA, Williams SK. Stimulation of angiogenesis by canine parathyroid tissue. Surgery 1996; 120: 1089-94.
    CrossrefPubMedGoogle Scholar
  • 22 Rogers P, Webb GP. Estimation of body fat in normal and obese mice. Br J Nutr 1980; 43: 83-6.
    CrossrefPubMedGoogle Scholar
  • 23 Lijnen HR, Maquoi E, Demeulemeester D, Van Hoef B, Collen D. Modulation of fibrinolytic and gelatinolytic activity during adipose tissue development in a mouse model of nutritionally induced obesity. Thromb Hae-most 2002; 88: 345-53.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 24 Coleman DL. Diabetes-obesity syndromes in mice. Diabetes 1982; 31: 1-6.
    CrossrefPubMedGoogle Scholar
  • 25 West DB, Boozer CN, Moody DL, Atkinson RL. Dietary obesity in nine inbred mouse strains. Am J Physiol 1992; 262: R1025-32.
    PubMedGoogle Scholar
  • 26 Surwit RS, Feinglos MN, Rodin J, Sutherland A, Petro AE, Opara EC, Kuhn CM, Rebuffé-Scrive M. Differential effects of fat and sucrose on the development of obesity and diabetes in C57BL/6J and A/J mice. Metabolism 1995; 44: 645-51.
    CrossrefPubMedGoogle Scholar
  • 27 Lijnen HR, Silence J, Van Hoef B, Collen D. Stromelysin-1 (MMP-3)-independent gelatinase expression and activation in mice. Blood 1998; 91: 2045-53.
    PubMedGoogle Scholar
  • 28 Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature 1998; 395: 763-70.
    CrossrefPubMedGoogle Scholar
  • 29 Gregoire FM, Smas CM, Sui HS. Understanding adipocyte differentiation. Physiol Rev 1998; 78: 783-809.
    CrossrefPubMedGoogle Scholar
  • 30 Pujuguet P, Simian M, Liaw J, Timpl R, Werb Z, Bissell M. Nidogen-1 regulates laminin-1-dependent mammary-specific gene expression. J Cell Sci 2000; 113: 849-58.
    PubMedGoogle Scholar
  • 31 Clouthier DE, Comerford SA, Hammer RE. Hepatic fibrosis, glomerulosclerosis, and a lipodystrophy-like syndrome in PEPCK-TGF-β1 transgenic mice. J Clin Invest 1997; 100: 2697-713.
    CrossrefPubMedGoogle Scholar
  • 32 Lijnen HR, Ugwu F, Bini A, Collen D. Generation of an angiostatin-like fragment from plasminogen by stromelysin-1 (MMP-3). Biochemistry 1998; 37: 4699-702.
    CrossrefPubMedGoogle Scholar
  • 33 Williams G, Bing C, Cai XJ, Harrold JA, King PJ, Liu XH. The hypothalamus and the control of energy homeostasis: different circuits, different purposes. Physiol Behav 2001; 74: 683-701.
    CrossrefPubMedGoogle Scholar