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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:78.)
© 2003 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Nutritionally Induced Obesity Is Attenuated in Transgenic Mice Overexpressing Plasminogen Activator Inhibitor-1

H. Roger Lijnen^*; Erik Maquoi^*; Pierre Morange; Gabor Voros; Berthe Van Hoef; Francis Kopp; Désiré Collen; Irène Juhan-Vague; Marie-Christine Alessi

From the Center for Molecular and Vascular Biology (H.R.L., E.M., G.V., B.V.H., D.C.), University of Leuven, Belgium; Haematology Laboratory (P.M., I.J.-V., M.C.A.), CHU Timone and INSERM EPI 9936, Marseille, France; and Histology Laboratory (F.K.), CHU Timone, Marseille, France.

Correspondence to H. Roger Lijnen, Center for Molecular and Vascular Biology, University of Leuven, Campus Gasthuisberg, O&N, Herestraat 49, B-3000 Leuven, Belgium. E-mail roger.lijnen{at}med.kuleuven.ac.be

Objective— The objective of this study was to investigate the role of plasminogen activator inhibitor-1 (PAI-1) in adipose tissue development in vivo.

Methods and Results— Transgenic (Tg) mice overexpressing murine PAI-1 under control of the adipocyte promoter aP2 and wild-type (WT) controls were kept on standard food (SFD) or on high-fat diet (HFD) for 15 weeks. The body weight and the weight of the isolated subcutaneous and gonadal fat deposits of the Tg mice kept on the HFD were significantly lower than those of the WT mice. The number of adipocytes in the adipose tissue was similar for Tg and WT mice on the HFD, but adipocyte hypotrophy and a significantly lower ratio of stroma cells/adipocytes were observed in the Tg mice. A significant negative correlation (P<0.01) was observed between expression of preadipocyte factor-1, which blocks adipocyte differentiation, and adipose tissue weight. Fasting insulin and total cholesterol levels on the HFD were lower in Tg than in WT mice.

Conclusions— High circulating PAI-1 levels attenuate nutritionally induced obesity. This may be related to modifications in adipose tissue cellularity affecting weight and plasma metabolic parameters.

Key Words: plasminogen activator inhibitor-1 • obesity • adipose tissue • adipocyte

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