The combination of experimental validation of glp-1 as an obesity gene in C. elegans with our database analyses showing that expression of NOTCH4 and EYS negatively correlates with BMI and other markers of metabolic disease in mice and humans, puts the spotlight on NOTCH4 and EYS as potential anti-obesity targets. Here, NOTCH4 is linked to obesity due to melanocortin 4 receptor deficiency.