Interestingly, while exendin-4 (a GLP-1 agonist) elicited preserved insulin release under a chow diet despite macrophage Gq activation, the same response was blunted in HFD-fed mice, indicating that obesity sensitizes β-cells to this inhibitory pathway (Figure 2). Here, GLP1R is linked to obesity due to melanocortin 4 receptor deficiency.