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THE ENDOCANNABINOID SYSTEM AND CB1 MECHANISM OF ACTION Excess food intake - obesity Overactivity of the EC system Brain Rimonabant X Rimonabant CB1 X Gastrointestinal tract ? Food intake CB1 Genetic susceptibility? Rimonabant Rimonabant Abdominal adiposity X Liver FFA X Adipocytes Skeletal muscle? Adiponectin CB1 FFA TNF-α CB1 CB1 IL-6 X Rimonabant CRP Lipogenesis Liver fat LPL Lipogenesis Improved insulin action VLDL Glucose production Insulin degradation Insulinemia Apo AI synthesis Improved glucose tolerance • Decreased waist (abdominal obesity) • Improved insulin sensitivity and glucose tolerance • Triglycerides and • Reduced inflammation HDL choIesteroI Risk of CVD and type 2 diabetes Source: International Chair on Cardiometabolic Risk www.cardiometabolic-risk.org Adapted from Després JP et al. Int J Obes 2006; 30: S44-52
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