However, the absence of effects of long-term hypercaloric diet intake and of CSN resection clearly led to the idea that further research is needed to understand the contribution of GLP-1 and GLP-1R to dysmetabolic states induced by hypercaloric diets, those that better mimic human metabolic diseases, such as obesity and type 2 diabetes. This evidence concerns the gene GLP1R and obesity due to melanocortin 4 receptor deficiency.