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Thromb Haemost 2006; 95(01): 174-181
DOI: 10.1160/TH05-07-0478
Animal Models
Schattauer GmbH

Impairment of adipose tissue development by hypoxia is not mediated by plasminogen activator inhibitor-1

Fabrizio Semeraro
1   Center for Molecular and Vascular Biology, KU Leuven, Leuven, Belgium
,
Gabor Voros
1   Center for Molecular and Vascular Biology, KU Leuven, Leuven, Belgium
,
Désiré Collen
1   Center for Molecular and Vascular Biology, KU Leuven, Leuven, Belgium
,
H. Roger Lijnen
1   Center for Molecular and Vascular Biology, KU Leuven, Leuven, Belgium
› Author AffiliationsFinancial support: This study was supported financially by grants from the “Bijzonder Onderzoeksfonds KU Leuven” (OT/2003/48) and the Flemish Fund for Scientific Research (FWO-Vlaanderen, G. 0112.02). F. Semeraro was the recipient of a fellowship from the Faculty of Medicine, Università degli Studi di Bari, Italy.
Further Information

Publication History

Received 08 July 2005

Accepted after resubmission 14 November 2005

Publication Date:
28 November 2017 (online)

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Summary

Hypoxia in rodents and humans is associated with a reduction of body fat on the one hand, and with enhanced expression of plasminogen activator inhibitor-1 (PAI-1), the main inhibitor of the fibrinolytic system, on the other hand. It was the objective of this study to investigate whether impairment of adipose tissue development by hypoxia may be mediated by PAI-1. Five week old male wild-type (WT) C57Bl/6 mice were fed a standard (SFD) or high fat (HFD) diet and kept under normoxic or hypoxic (10% O2) conditions. In addition, PAI-1 deficient mice and WT littermates were kept on HFD under normoxia or hypoxia. In vitro, the effect of hypoxia (2% O2) was investigated on differentiation of 3T3-L1 cells into adipocytes. Hypoxia induced a significant reduction of weight gain in WT mice on either SFD or HFD, accompanied by lower weights of subcutaneous (SC) and gonadal (GON) fat. Under hypoxic conditions, adipocytes in the adipose tissues were significantly smaller, whereas blood vessel size and density were larger. Serum PAI-1 levels were enhanced in hypoxic mice on SFD but not on HFD, and overall did not correlate with the observed changes in adipose tissue composition. Furthermore, the effects of hypoxia on adipose tissue in mice on HFD were not affected by deficiency of PAI-1. The inhibiting effect of hypoxia on in vitro preadipocyte differentiation was not mediated by PAI-1 activity. In conclusion, impairment of in vivo adipose tissue development and in vitro differentiation of preadipocytes by hypoxia is not mediated by PAI-1.

Keywords

Hypoxia - PAI-1 - adipose tissue - obesity - (pre)adipocyte
 

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