Thromb Haemost 2006; 95(06): 1019-1024
DOI: 10.1160/TH05-11-0742
Animal Models
Schattauer GmbH

Overexpression of tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) in mice does not affect adipogenesis or adipose tissue development

Diego Demeulemeester
1  Center for Molecular and Vascular Biology, K.U. Leuven, Leuven, Belgium
,
Ilse Scroyen
1  Center for Molecular and Vascular Biology, K.U. Leuven, Leuven, Belgium
,
Gabor Voros
1  Center for Molecular and Vascular Biology, K.U. Leuven, Leuven, Belgium
,
Jan Snoeys
1  Center for Molecular and Vascular Biology, K.U. Leuven, Leuven, Belgium
,
Bart De Geest
1  Center for Molecular and Vascular Biology, K.U. Leuven, Leuven, Belgium
,
Désiré Collen
1  Center for Molecular and Vascular Biology, K.U. Leuven, Leuven, Belgium
,
H. Roger Lijnen
1  Center for Molecular and Vascular Biology, K.U. Leuven, Leuven, Belgium
› Author Affiliations
Financial support: This study was supported financially by grants from the Flemish Fund for Scientific Research (FWO, G.0112.02), the Institute for the promotion of Innovation through Science and Technology in Flanders (IWT Vlaanderen) and the “Bijzonder Onderzoeksfonds K. U. Leuven” (OT/03/48).
Further Information

Publication History

Received 16 November 2005

Accepted after resubmission 06 April 2006

Publication Date:
30 November 2017 (online)

Summary

In order to evaluate a potential functional role of tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) in development of obesity, we studied the effect of overexpression of human TIMP-1 (hTIMP-1) in C57Bl/6J mice in vivo and in 3T3-F442A preadipocytes in vitro. Stable long-term overexpression of hTIMP-1 in mice was achieved by adenoviral gene transfer, yielding plasma levels exceeding 250 ng/ml at eight weeks after injection. Mice overexpressing hTIMP-1 and kept on a high fat diet for 14 weeks had body weights, adipose tissue weights, and adipocyte diameters that were somewhat, but not significantly, lower than those of control mice. Similar observations were made after overexpression of hTIMP-1 in mice with lipectomy of the subcutaneous adipose tissue, kept on a high fat diet for 20 weeks. In both in vivo models, blood vessels in the adipose tissues were significantly smaller after hTIMP-1 gene transfer than in control mice. Overexpression of hTIMP-1 in 3T3-F442A preadipocytes had no effect on their subsequent differentiation into mature adipocytes. Thus, overexpression of hTIMP-1 in mice had no significant effect on ongoing adipogenesis or adipose tissue development, although the blood vessel size in adipose tissues was reduced.