Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play a role in 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. Local overexpression by injection of 3T3-F442A preadipocytes expressing human TIMP-1 (hTIMP-1) in the back of NUDE mice kept on high fat diet (HFD) for 4 weeks, had no effect on de novo formed fat pad mass. The fat pads formed from the hTIMP-1 expressing cells did show a significantly larger blood vessel size as compared to control cells (57 ± 4.8 µm2 vs 38 ± 1.4 µm2, p = 0.0017). No effect was observed on blood vessel density or on adipocyte size or density. Systemic overexpression of hTIMP-1 by injection in the tail vein of an adenoviral construct 3 days before injection of 3T3-F442A cells in the back of NUDE mice kept on HFD for 4 weeks, also 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 (1477 ± 44 µm2 vs 1285 ± 32 µm2, p = 0.03).
Thus, in vivo local or systemic hTIMP-1 overexpression did not significantly affect the extent of de novo adipose tissue formation, but the effect on angiogenesis appeared to be different. Local overexpression induced significantly larger blood vessel size associated with somewhat lower blood vessel density, whereas systemic overexpression was associated with significantly lower blood vessel density but did not affect blood vessel size.