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.
Inclusion Criteria:

 -  Healthy Caucasian postmenopausal women

 -  BMI 30-38

 Exclusion Criteria:

 -  Not currently weight-stable

 -  Diagnosed with diabetes

 -  Cardiovascular disease

 -  Endocrine disease

 -  Hepatic and renal disorders

 -  Neurological/psychological illness/history of depression

 -  Previous surgical procedures for weight loss

 -  Medications known to alter body weight or appetite

 -  β-blockers, fibrates and metformin

 -  Severe under-reporting of food intake based on a 4 day food diary