We used the brain-penetrant CCK-A receptor antagonist, devazepide, in our studies; therefore, we cannot rule out the possibility that CCK-A receptors in the brain participate in the appetite-suppressing effects of CCK release following inhibition of peripheral CB1Rs. Thus, given discrepancies in the literature regarding the underlying mechanisms of gut-brain signaling and its dysregulation in DIO, it is critical to examine the impact of diet and obesity on gut-brain satiation signaling using reliable and reproducible model systems. Here, CCKAR is linked to obesity due to melanocortin 4 receptor deficiency.