First Author | Lijnen HR | Year | 2007 |
Journal | J Thromb Haemost | Volume | 5 |
Issue | 11 | Pages | 2259-65 |
PubMed ID | 17958744 | Mgi Jnum | J:147926 |
Mgi Id | MGI:3842909 | Doi | 10.1111/j.1538-7836.2007.02735.x |
Citation | Lijnen HR, et al. (2007) Deficiency of plasminogen activator inhibitor-2 impairs nutritionally induced murine adipose tissue development. J Thromb Haemost 5(11):2259-65 |
abstractText | BACKGROUND: A functional role for several components of the fibrinolytic (plasminogen/plasmin) system in development of adipose tissue has been demonstrated. No information is available, however, on a potential role of plasminogen activator inhibitor-2 (PAI-2) in obesity. METHODS: In vitro, 3T3-F442A murine pre-adipocytes were differentiated into mature adipocytes. In vivo, 5-week-old male PAI-2-deficient (PAI-2(-/-)) mice and wild-type (WT) controls of the same genetic background (C57Bl/6) were kept on a high fat diet (HFD, caloric value of 20.1 kJ g(-1)) for 15 weeks. RESULTS: Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) revealed expression of PAI-2 mRNA during in vitro differentiation of pre-adipocytes and in vivo in s.c. and gonadal (GON) adipose tissues of WT mice, where it was localized both in the stromal/vascular cell fraction and in adipocytes. During HFD feeding, food intake and body weight gain were comparable for WT and PAI-2(-/-) mice. Subcutaneous plus GON fat mass was, however, significantly lower in PAI-2(-/-) mice (3.15 +/- 0.21 vs. 3.91 +/- 0.18 g; P < 0.05). Immunohistochemical analysis of adipose tissues revealed significant adipocyte hypotrophy in s.c. fat of PAI-2(-/-) mice (about 25% reduction in size; P < 0.01). Blood vessel density, normalized to adipocyte number, was comparable in s.c. fat, but was lower (P < 0.05) in GON fat of PAI-2(-/-) mice. Adipose tissue-associated fibrinolytic activity was not affected by PAI-2 deficiency. CONCLUSION: PAI-2 promotes adipose tissue development in mice via a mechanism independent of its antifibrinolytic effect. |