In this study, we evaluated a novel amide derivative of oleic acid and tyrosol (Oleyl hydroxytyrosol ether, OLHHA), a PPARα agonist, and CB1 antagonist, in combination with the GLP-1 agonist liraglutide (LIG), as an effective multitarget therapy to improve both the peripheral and central alterations in an animal model of diet-induced obesity. The gene discussed is CNR1; the disease is obesity due to melanocortin 4 receptor deficiency.