1. Adiponectin is required to mediate rimonabant-induced improvement of insulin sensitivity but not body weight loss in diet-induced obese mice.
- Author
-
Migrenne S, Lacombe A, Lefèvre AL, Pruniaux MP, Guillot E, Galzin AM, and Magnan C
- Subjects
- Adiponectin deficiency, Adiponectin genetics, Adiponectin metabolism, Animals, Dietary Fats, Disease Models, Animal, Eating drug effects, Glucose metabolism, Glucose Tolerance Test, Hyperinsulinism etiology, Hyperinsulinism metabolism, Hyperinsulinism physiopathology, Insulin blood, Intra-Abdominal Fat drug effects, Intra-Abdominal Fat metabolism, Lipids blood, Liver drug effects, Liver metabolism, Male, Mice, Mice, Knockout, Obesity etiology, Obesity metabolism, Obesity physiopathology, Rimonabant, Subcutaneous Fat drug effects, Subcutaneous Fat metabolism, Anti-Obesity Agents pharmacology, Hyperinsulinism prevention & control, Insulin Resistance, Obesity drug therapy, Piperidines pharmacology, Pyrazoles pharmacology, Weight Loss drug effects
- Abstract
The increase in adiponectin levels in obese patients with untreated dyslipidemia and its mRNA expression in adipose tissue of obese animals are one of the most interesting consequences of rimonabant treatment. Thus, part of rimonabant's metabolic effects could be related to an enhancement of adiponectin secretion and its consequence on the modulation of insulin action, as well as energy homeostasis. The present study investigated the effects of rimonabant in adiponectin knockout mice (Ad(-/-)) exposed to diet-induced obesity conditions. Six-week-old Ad(-/-) male mice and their wild-type littermate controls (Ad(+/+)) were fed a high-fat diet for 7 mo. During the last month, animals were administered daily either with vehicle or rimonabant by mouth (10 mg/kg). High-fat feeding induced weight gain by about 130% in both wild-type and Ad(-/-) mice. Obesity was associated with hyperinsulinemia and insulin resistance. Treatment with rimonabant led to a significant and similar decrease in body weight in both Ad(+/+) and Ad(-/-) mice compared with vehicle-treated animals. In addition, rimonabant significantly improved insulin sensitivity in Ad(+/+) mice compared with Ad(+/+) vehicle-treated mice by decreasing hepatic glucose production and increasing glucose utilization index in both visceral and subcutaneous adipose tissue. In contrast, rimonabant failed to improve insulin sensitivity in Ad(-/-) mice, despite the loss in body weight. Rimonabant's effect on body weight appeared independent of the adiponectin pathway, whereas adiponectin seems required to mediate rimonabant-induced improvement of insulin sensitivity in rodents.
- Published
- 2009
- Full Text
- View/download PDF