Insulin in the Central Nervous System: A Regulator of Appetite and Body Weight

Abstract

Although numerous potentially physiologic actions of insulin in the central nervous system (CNS) have been identified at the cellular level, the consequences of these actions at the level of the organism have not been defined. In this chapter we advance the hypothesis that insulin may act as a regulator of body weight. In 1979, Woods and Porte suggested that insulin levels in the cerebrospinal fluid (CSF) may act as an indicator of body adiposity and provide a negative feedback signal to regulate body weight on a long term basis.1,2 This hypothesis was based upon three lines of experimental evidence: First, basal plasma insulin levels are correlated with body adiposity. Second, CSF insulin levels represent a slow integral over time of plasma levels, with rapid fluctuations in plasma insulin levels being damped. Third, direct infusion of insulin into the CSF and into certain brain sites can result in a decrease of food intake and body weight. These three lines of evidence will be reviewed. Additionally, this chapter will provide some discussion of the possible regulation involved in generating and sensing this signal, as well as possible defects in the brain insulin system in a genetically obese rat model. Readers who wish specific discussion of issues surrounding the brain insulin system are referred to the chapters in this text by LeRoith, Heidenreich, and Raizada, and to a recent review.3