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 µm² vs. 1,285 ± 32 µm², 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.