Thrombosis and Haemostasis vol:101 issue:2 pages:388-393
To study the functional role of plasminogen activator inhibitor-1 (PAI-1) in obesity, the effect of its overexpression on de novo adipogenesis was evaluated in murine models in vivo. Therefore, 3T3-F442A preadipocytes overexpressing murine PAI-1 (mPAI-1) or control cells were injected in the back of male NUDE mice, which were fed a high fat diet (HFD) for 4 weeks. De novo fat pads that formed from the PAI-1 overexpressing cells were larger (21 ± 2.4 mg vs 14 ± 1.4 mg; p = 0.017) and showed a higher adipocyte density (373 ± 28 mm-2 vs 301 ± 12 mm-2; p = 0.03) as compared to those formed from control cells.
In a second model, male NUDE mice were injected in the tail vein with an adenoviral construct expressing mPAI-1 or with the empty vector, and 3 days later with 3T3-F442A cells. After 4 weeks of HFD, total body weight and de novo fat pad weight were comparable for both groups. Mild adipocyte hypotrophy was observed in the de novo fat pads of the PAI-1 overexpressing mice (1180 ± 33 µm2 vs 1285 ± 32 µm2; p= 0.024), whereas the blood vessel size was significantly smaller than in controls (30 ± 1.8 µm2 vs 63 ± 3.6 µm2; p < 0.0001).
Thus, the effect of local or systemic PAI-1 overexpression on adipocyte or blood vessel size and density of de novo formed fat pads appears to be different. Whereas local overexpression resulted in larger fat pads, systemic overexpression had no effect on de novo adipogenesis, although angiogenesis appeared to be impaired.