期刊
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
卷 5, 期 11, 页码 2259-2265出版社
WILEY
DOI: 10.1111/j.1538-7836.2007.02735.x
关键词
adipose tissue; obesity; PAI-2
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 (C57B1/6) 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.
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