Insulin acts throughout the body to reduce circulating energy and to increase energy storage. Within the brain, insulin produces a net catabolic effect by reducing food intake and increasing energy expenditure; this is evidenced by the hypophagia and increased brown adipose tissue sympathetic nerve activity induced by central insulin infusion. Reducing the activity of the brain insulin system via administration of insulin antibodies, receptor antisense treatment, or receptor knockdown results in hyperphagia and increased adiposity. However, despite decades of research into the role of central insulin in food intake, many questions remain to be answered, including the underlying mechanism of action.