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H. Roger Lijnen, Diego Demeulemeester, Berthe Van Hoef, Dsir Collen, Erik Maquoi
Deficiency of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) impairs nutritionally induced obesity in mice
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.
Thrombosis and Haemostasis, Schattauer
Print ISSN: 0340-6245
Volume: 89
Pages: 249 - 255