Tiplaxtinin impairs nutritionally induced obesity in mice.
To investigate the effect of tiplaxtinin, designed as a synthetic inhibitor of plasminogen activator inhibitor-1 (PAI-1), on obesity, male C57Bl/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.
Lijnen
H Roger
HR
Center for Molecular and Vascular Biology, KU Leuven, Campus Gasthuisberg, O & N 1, Box 911, Herestraat 49, B-3000 Leuven, Belgium. roger.lijnen@med.kuleuven.be
Alessi
Marie-Christine
MC
Frederix
Liesbeth
L
Collen
Désiré
D
Juhan-Vague
Irène
I
D000273:Adipose Tissue / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects*; D004041:Dietary Fats; D004195:Disease Models, Animal; D002149:Energy Intake; D005342:Fibrinolysis / Q000187:drug effects; D005951:Glucose Tolerance Test; D007210:Indoleacetic Acids / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000378:metabolism; D009765:Obesity / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009929:Organ Size / Q000187:drug effects; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D013997:Time Factors
D019440:Anti-Obesity Agents; D001786:Blood Glucose; D004041:Dietary Fats; D007210:Indoleacetic Acids; D007328:Insulin; D008055:Lipids; D017395:Plasminogen Activator Inhibitor 1; C488103:tiplaxtinin