The CB1R-dependent and independent mechanisms engaged by the CB1R antagonist Rimonabant and operating directly at the adipocytes for stimulation of lipolysis, as reported here, may be of potential value for the future identification of novel targets and drug candidates for anti-obesity/diabetes therapy on basis of the pharmacological aim of lipolysis stimulation. This evidence concerns the gene CNR1 and obesity due to melanocortin 4 receptor deficiency.