Blood vessel density in de novo formed adipose tissue is decreased upon overexpression of TIMP-1.

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play a role in the development of obesity by contributing to adipogenesis, angiogenesis, and extracellular matrix degradation. We have evaluated a potential functional role of TIMP-1, which inhibits most MMPs, in in vivo adipogenesis. Therefore, human (h) TIMP-1 was overexpressed by injection in the tail vein of NUDE mice of an adenoviral vector 3 days before injection of 3T3-F442A preadipocytes in the back. After 4 weeks of high-fat diet, the de novo formed fat was analyzed. Overexpression of hTIMP-1 had no effect on de novo formed fat pad mass. However, the blood vessel density of the fat pads from mice overexpressing hTIMP-1 was significantly lower than in controls (587 +/- 11 mm(-2) vs. 806 +/- 20 mm(-2), P < 0.0001) whereas the adipocytes were somewhat larger (1,477 +/- 44 microm(2) vs. 1,285 +/- 32 microm(2), P = 0.03). Thus, in vivo hTIMP-1 overexpression did not significantly affect the extent of de novo adipose tissue formation, but was associated with significantly lower blood vessel density.