Thus, although the correlation data coupled with the GKO and ghrelin cell ablation data suggest that the reduced ghrelin in diet-induced obesity contributed to islet enlargement, the presence of larger islets in HFD-fed GKO mice suggests that diet-induced obesity–associated islet enlargement was not solely mediated by reduced ghrelin. Here, GHRL is linked to obesity due to melanocortin 4 receptor deficiency.