Brain energy consumption induced by electrical stimulation increases systemic glucose tolerance in normal-weight men. In obesity, fundamental reductions in brain energy levels, gray matter density, and cortical metabolism, as well as chronically impaired glucose tolerance, suggest that disturbed neuroenergetic regulation may be involved in the development of overweight and obesity. Here, we induced neuronal excitation by anodal transcranial direct current stimulation versus sham, examined cerebral energy consumption with ³¹P magnetic resonance spectroscopy, and determined systemic glucose uptake by euglycemic-hyperinsulinemic glucose clamp in 15 normal-weight and 15 obese participants. We demonstrate blunted brain energy consumption and impaired systemic glucose uptake in obese compared with normal-weight volunteers, indicating neuroenergetic dysregulation in obese humans. Broadening our understanding of reduced multifocal gray matter volumes in obesity, our findings show that reduced appetite- and taste-processing area morphometry is associated with decreased brain energy levels. Specifically, gray matter volumes of the insula relate to brain energy content in obese participants. Overall, our results imply that a diminished cerebral energy supply may underlie the decline in brain areas assigned to food intake regulation and therefore the development of obesity.