The Effect of Rimonabant on Energy Expenditure, Fat Metabolism and Body Composition
The Effect of Rimonabant on Energy Expenditure, Fat Metabolism and Body Composition
This study will determine in obese subjects the direct effects of the weight loss drug rimonabant (ie independent of weight loss) on energy expenditure, fat metabolism and and body fat distribution. We hypothesise that rimonabant will increase energy expenditure. The fuel for the increased energy expenditure will come from fat. As a result of burning more fat there will be a decrease in fat in blood and an improvement in the body's response to insulin.
In obese subjects (BMI 33-38kg/m2) completing 12 months of treatment with the CB1 antagonist rimonabant (SR141716) there was an average weight loss from baseline of approximately 8.5 kg. These studies also showed the weight loss was accompanied by a decrease in plasma triglyceride (TG), an increase in HDL cholesterol and an improvement in insulin sensitivity measured by HOMA-IR. When adjusted for weight loss 50% of the improvements in TG, HDL cholesterol, and insulin sensitivity was not attributable to weight loss. This suggests that rimonabant has direct effects on fat metabolism.
This study will investigate the direct effects of rimonabant (ie independent of weight loss) in a 2 group randomised study. One group will receive rimonabant for 12 weeks and the other group will have a dietary intervention to match the weight loss in the rimonabant group. Measurements of energy expenditure (using indirect calorimetry and Actiheart monitors),fatty acid and triglyceride metabolism (using stable isotope techniques) and body fat distribution (by magnetic resonance imaging) will be made before and after the intervention. To determine the possible mechanisms of the changes in metabolism, gene expression of key regulators of fatty acid metabolism in adipose and muscle tissue and circulating levels of adipokines will be measured.
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