Deficiency of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) impairs nutritionally induced obesity in mice.

[en] Tissue inhibitor of matrix metalloproteinase-1 deficient (TIMP-1(-/-)) mice and wild-type (TIMP-1(+/+)) controls were kept on a standard (SFD) or a high fat diet (HFD) for 15 weeks. At the time of sacrifice, TIMP-1(-/-) mice on HFD had a significantly lower body weight (29 +/- 1.5 versus 41 +/- 1.8 g, p <0.005), and significantly less subcutaneous (0.81 +/- 0.19 versus 1.78 +/- 0.21 g, p <0.05) and gonadal (0.87 +/- 0.17 versus 1.85 +/- 0.18 g, p <0.005) fat mass. These differences were much less pronounced for mice on SFD. On HFD but not on SFD, adipocyte diameters were significantly lower in the adipose tissue of TIMP-1(-/-) mice. Plasma leptin levels in TIMP-1(-/-) mice on HFD were significantly lower as compared to TIMP-1(+/-) mice, and strongly correlated with adipose tissue mass for both genotypes. Staining with an endothelial cell specific lectin revealed a significantly higher blood vessel density, larger stained area and vessel size in adipose tissue of TIMP-1(-/-) mice on HFD. This difference disappeared after normalization to the adipocyte number, suggesting that it does not represent a true enhancement of angiogenesis. Thus, in a murine model of nutritionally induced obesity, TIMP-1 promotes adipose tissue development.

Disciplines :

Endocrinology, metabolism & nutrition

Author, co-author :

Lijnen, Roger

Demeulemeester, Diego

Van Hoef, B.

Collen, Désiré

Maquoi, Erik ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement

Language :

English

Title :

Deficiency of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) impairs nutritionally induced obesity in mice.

Publication date :

February 2003

Journal title :

Thrombosis and Haemostasis

ISSN :

0340-6245

eISSN :

2567-689X

Publisher :

Schattauer Gmbh-Verlag Medizin Naturwissenschaften, Stuttgart, Germany

Volume :

Issue :

Pages :

249-255

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 10 November 2011

Statistics

Number of views

246 (1 by ULiège)

Number of downloads

449 (2 by ULiège)

More statistics

Scopus citations^®

Scopus citations^®
without self-citations

OpenCitations

OpenAlex citations

Bibliography

Crandall DL, Hausman GJ, Kral JG. A review of the microcirculation of adipose tissue: Anatomic, metabolic, and angiogenic perspectives. Microcirculation 1997; 4: 211-32.
Dollery CM, McEwan JR, Henney AM. Matrix metalloproteinases and cardiovascular disease. Circ Res 1995; 77: 863-8.
Carmeliet P, Collen D. Development and disease in proteinase-deficient mice: Role of the plasminogen, matrix metallopreteinase and coagulation. Thromb Res 1998; 91: 255-85.
Lijnen HR. Molecular interactions between the plasminogen/plasmin and matrix metallo-proteinase systems. Fibrinolysis & Proteolysis 2000; 14: 175-81.
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.
Lijnen HR, Maquoi E, Holvoet P, Mertens A, Lupu F, Morange P, Alessi MC, Juhan-Vague I. Adipose tissue expressin of gelatinases in mouse models of obesity. Thromb Haemost 2001; 85: 1111-1116.
Boulomié A, Sengés C, Portolan G, Galitzky J, Lafontan M. Adipocyte produces matrix metalloproteinase 2 and 9. Involvement in adipocyte differentiation. Diabetes 2001; 50: 2080-6.
Willenbrock F, Murphy G. Structure-function relationships in the tissue inhibitors of metalloproteinases. Am J Respir Crit Care Med 1994; 150: S165-70.
Greene J, Wang MS, Liu YLE, Raymond LA, Rosen C, Shi YNE. Molecular cloning and characterization of human tissue inhibitor of metalloproteinase 4. J Biol Chem 1996; 271: 30375-80.
Maquoi E, Munaut C, Colige A, Colen D, Lijnen HR. Modulation of the expression of murine matrix metalloproteinases and their tissue inhibitors with obesity. Diabetes 2002; 51: 1093-101.
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 Haemost 2002; 88: 345-53.
Soloway PD, Alexander CM, Web Z, Jaenisch R. Targeted mutagenesis of TIMP-1 reveals that lung tumor invasion is influenced by TIMP-1 genotype of the tumor but not by that of the host. Oncogene 1996; 13: 2307-14.
Nothnick WB, Soloway P, Curry TE. Assessment of the role of tissue inhibitor of metallo-proteinase-1 (TIMP-1) during the periovulator period in female mice lacking a function-al TMP-1 gene. Biol Reprod 1997; 56: 1181-8.
Giles AR. Guidelines for the use of animals in biomedical research. Thromb Haemost 1987; 58: 1078-84.
Laitinen L. Griffonia simplicifolia lectins bind specifically to endothelial cells and some epithelial cells in mouse tissues. Histochem J 1987; 19: 225-34.
Lijnen HR, Van Hoef B, Lupu F, Moons L, Carmeliet P, Collen D. Function of plasminogen/plasmin and matrix metalloproteinase systems after vascular injury in mice with targeted inactivation of fibrinolytic system genes. Arterioscler Thromb Vasc Biol 1998; 18: 1035-45.
Kleiner DE, Stetler WG. Quantitative zymography: Detection of picogram quantities of gelatinases. Anal Biochem 1994; 218: 325-29.
Gallis 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.
Decklerck 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.
Rogers P, Webb GP. Estimation of body fat in normal and obese mice. Br J Nutr 1980; 43: 83-6.
Lijnen HR, Maquoi E, Hansen LB, Van Hoef B, Frederix L, Collen D. Matrix metalloproteinase inhibition impairs adipose tissue development in mice. Arterioscler Thromb Vasc Biol 2002; 22: 374-9.
Rupnick MA, Panigrahy D, Zhang C-Y, Dallabrida SM, Lowell BB, Langer R, Folkman MJ. Adipose tissue mass can be regulated through the vasculature. Proc Natl Acad Sci USA 2002; 99: 10730-5.
Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature 1998; 395: 763-70.
Maquoi E, Demeulemeester D, Vörös G, Collen D, Lijnen HR. Enhanced nutritionally induced adipose tissue development in mice with stromelysin-1 gene inactivation. Thromb Haemost 2003; 89 (in press).
Hlatky L, Hahnfeldt P, Folkman J. Clinical application of antiangiogenic therapy: Micro-vessel density, what it does and dosen't tell us. J Natl Cancer Inst 2002; 94: 883-93.
Cao R, Brakenhielm E, Wahlestedt C, Thyberg J, Cao Y. Leptin induces vascular permeability and synergistically stimulates angiogenesis with FGF-2 and VEGF. Proc Natl Acad Sci USA 2001; 98: 6390-5.
Hayakawa T, Yamashita K, Tanzawa K, Uchijima E, Iwata K. Growth-promoting activity of tissue inhibitor of metalloproteinase-1 (TIMP-1) for a wide range of cells. A possible new growth factor in serum. Febs Lett 1992; 298: 29-32.
Zhao WO, Li H, Yamashita K, Guo XK, Hoshino T, Yoshida S, Shinya T, Hayakawa T. Cell cycle-associated accumulation of tissue inhibitor of metalloproteinase-1 (TIMP-1) in the nuclei of human gingival fibroblasts. J Cell Sci 1998; 111: 1147-53.