We also provide a theoretical explanation for weight loss in PD by linking metabolism and energy homeostasis with olfactory dysfunction in PD, based on the following: (1) the olfactory system is a metabolic sensor of brain insulin and glucose levels, playing a role in controlling energy homeostasis in response to both sensory (external) and hormonal (internal) signals15,16; (2) α-synuclein pathology in PD likely first appears in the olfactory bulb17,18; and (3) impaired sense of smell is very often the first manifestation of prodromal PD19. This evidence concerns the gene INS and Parkinson disease.