Thrombosis and Haemostasis vol:96 issue:6 pages:731-737
date:Katholieke Univ Leuven, Ctr Mol & Vasc Biol, B-3000 Louvain, Belgium; INSERM, U626, Haematol Lab, F-13258 Marseille, France; Fac Med Marseille, F-13385 Marseille, France
To investigate the effect of tiplaxtinin, designed as a synthetic inhibitor of plasminogen activator inhibitor-I (PAI-I), on obesity, male C57BI/6 mice (13-14 weeks old) were kept on a high-fat diet (20.1 kJ/g) for four weeks without or with addition of tiplaxtinin (PAI-039) at a dose of 2 mg/g food. At the time of sacrifice, body weights were significantly lower in the inhibitor-treated mice (p < 0.0005). The weights of the isolated subcutaneous and gonadal fat deposits were also significantly lower (both p < 0.0005), associated with adipocyte hypotrophy. Inhibitor-treated adipose tissues displayed similar blood vessel size, but a higher blood vessel density. Fasting glucose and insulin levels, as well as glucose-tolerance tests were not significantly affected by the inhibitor treatment, whereas plasma triglyceride levels were significantly reduced (p = 0.02) and LDL-cholesterol levels significantly enhanced (p = 0.0002). Insulin-tolerance tests revealed significantly lower glucose levels at the end of the test in the inhibitor treated mice (p = 0.03). Thus, in this model of diet-induced obesity in mice administration of tiplaxtinin resulted in impaired adipose tissue development.