Deficiency of plasminogen activator inhibitor-2 impairs nutritionally induced murine adipose tissue development.
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.


CONCLUSIONS
PAI-2 promotes adipose tissue development in mice via a mechanism independent of its antifibrinolytic effect.
Lijnen
H R
HR
Center for Molecular and Vascular Biology, KU Leuven, Leuven, Belgium. roger.lijnen@med.kuleuven.be
Frederix
L
L
Scroyen
I
I
D016475:3T3 Cells; D050156:Adipogenesis; D000273:Adipose Tissue / Q000254:growth & development*; D000818:Animals; D004032:Diet; D002149:Energy Intake; D005342:Fibrinolysis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017396:Plasminogen Activator Inhibitor 2 / Q000032:analysis / Q000172:deficiency* / Q000502:physiology*
D017396:Plasminogen Activator Inhibitor 2