Control of energy homeostasis: role of enzymes and intermediates of fatty acid metabolism in the central nervous system

Abstract

The regulation of energy homeostasis is critical for normal physiology and survival. Energy flux must be rigorously monitored and adjusted to ensure that fuel intake and expenditure remain within acceptable limits. The central nervous system (CNS) is, in large part, responsible for conducting this energy-monitoring function and for integrating the numerous inputs. It has become evident that neurons of the CNS monitor and respond to levels of metabolic intermediates that reflect peripheral energy status. Intermediates in the fatty acid biosynthetic pathway have been implicated as hypothalamic signaling mediators that sense and respond to changes in circulating fuels. Genetic and pharmacologic manipulation of the enzymes of fatty acid metabolism have led to the hypothesis that neuronal metabolic intermediates affect neural outputs that modify both feeding behavior and energy expenditure. This review focuses on the regulatory roles of these enzymes and intermediates in the regulation of food intake and energy balance.