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Thromb Haemost 2009; 101(02): 388-393
DOI: 10.1160/TH08-06-0401
DOI: 10.1160/TH08-06-0401
Animal Models
Effect of plasminogen activator inhibitor-1 on adipogenesis in vivo
Financial support: This study was supported financially by the Institute for the promotion of Innovation through Science and Technology in Flanders (IWT-Vlaanderen) (SBO project 040084), and by the Interuniversity Attraction Poles (IAP P6/30). The Center for Molecular and Vascular Biology is supported by the “Excellentie financiering KULeuven” (EF/05/013).
Further Information
Publication History
Received:
23 June 2008
Accepted after major revision:
14 January 2008
Publication Date:
23 November 2017 (online)
Summary
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 expressing 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 four weeks. De novo fat pads that formed from the PAI-1 expressing 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 three days later with 3T3-F442A cells. After four 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 (over)expression on adipocyte or blood vessel size and density of de novo formed fat pads appears to be different, and concentration-dependent. Whereas local expression resulted in larger fat pads, systemic overexpression had no effect on de novo adipogenesis, although angiogenesis appeared to be impaired.
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