A re-assessment of the regulation of adiposity and appetite by the brain insulin system.

We have provided strong support for the hypothesis that the pancreatic hormone, insulin, provides a signal to the brain indicating the level of adiposity. Because insulin is found in the cerebrospinal fluid (CSF) in direct proportion to plasma levels, and because changes of plasma insulin result in subsequent changes of CSF insulin, we previously hypothesized that the blood-borne insulin signal enters the central nervous system by initially entering the CSF and then diffuses into the brain. Such a route explained the time lag for influences of insulin upon food intake and body weight. Recent evidence suggests that insulin may enter the brain directly through brain capillaries, raising the possibility that what is measured in the CSF may not be indicative of insulin on its way into critical brain areas. Implications of this change of route of entry of insulin into the brain for the regulation of food intake and body weight are discussed.