Interestingly, the Sisley group generated mice with glutamatergic neuronal deletion of GLP-1R and observed that GLP-1R agonists successfully execute glucose-lowering effects but fail to induce weight loss (Sisley et al., 2014), suggesting that the brain may control the anti-obesity actions of GLP-1. Here, GCG is linked to obesity due to melanocortin 4 receptor deficiency.