Chronic intracerebroventricular infusion of insulin reduces food intake and body weight of baboons

Body adiposity is normally maintained within rigid limits1–3. Although it is not clear that this regulation fits a strict negative feedback pattern, animals do maintain a relatively constant body adiposity4. It has been postulated that this regulation is mediated by some signal which informs centres controlling food intake, probably located in the brain, as to the present state of adiposity5,6. The identity of the signal is unknown, but the direct correlation between body adiposity and basal insulin levels in the plasma7–9, suggests insulin as a possible candidate. This hormone is present in the cerebrospinal fluid (CSF) of many species10–13, and is a slow integral over time of the level within the plasma14. Thus, the level of insulin in the CSF is relatively resistant to short-term plasma fluctuations of insulin. Obese humans have higher levels of CSF insulin than lean controls and the CSF insulin level of both obese and lean humans is reduced proportionately after a prolonged fast15. We have therefore postulated16 that the feedback system responding to body adiposity uses the concentration of insulin in the CSF as a major signal. Additional support for such a role is found in recent reports that insulin receptors are present in several regions of the brain and spinal cord17–20. We now present additional evidence for our hypothesis by showing that in baboons the infusion of exogenous insulin into the CSF elicits a reliable and predictable decrease in food intake and body weight.