Whether such intervention can modulate brain insulin sensitivity in older age is particularly questionable given that changes in function and distribution of adipose tissue can trigger metabolic alterations such as hyperinsulinemia (Palmer and Kirkland, 2016; Tchkonia et al., 2010) and relevant brain circuits for central insulin action like the dopaminergic mesolimbic pathway undergo age-related changes (Karrer et al., 2017). This evidence concerns the gene INS and hyperinsulinism.