Interestingly, Duca et al. found that high-energy (HE)/high-fat (HF) feeding led to significant downregulation of GLP-1R expression in the vagal nodose ganglia of obesity-prone (OP) but not obesity-resistant (OR) rats and that the combination of HE/HF feeding and the OP phenotype led to reduced endogenous GLP-1 and GLP-1R activation [7]. Here, GCG is linked to obesity due to melanocortin 4 receptor deficiency.