Since exogenous Gdf15 injection ameliorated the obesity phenotype in obese animal models [54], therapeutic strategies targeting Gdf15 or its upstream regulator SIK2 in POMC neurons of the obese human brain will require the identification of differences in the Gdf15-GFRAL axis between the two species. This evidence concerns the gene GFRAL and obesity due to melanocortin 4 receptor deficiency.