To dissect the relative contribution of PI3Kɑ and PI3Kδ inhibition in the reduction of obesity, we treated obese hyperphagic ob/ob mice with a selective PI3Kɑ inhibitor, BYL-719 [13], or with a selective PI3Kδ inhibitor, GS-9820 (also known as CAL-120) [14]. Here, PIK3CA is linked to obesity due to melanocortin 4 receptor deficiency.