Although AT dysfunction certainly is an early consequence of Alms1 mutations, we cannot exclude the possibility that other systemic aberrations could contribute to the metabolic diseases in Alms1GT/GT and in ALMS patients, such as the impairment in leptin receptor trafficking resulting in leptin-resistance (similar to what was observed in Bardet Biedl syndrome [51]), the reduction of cilia number in the hypothalamus [52], or the alteration of insulin vesicle release mediated by centrosomal proteins in pancreatic β cells [53]. This evidence concerns the gene INS and metabolic disease.