Fuel sensing and the central nervous system (CNS): implications for the regulation of energy balance and the treatment for obesity

This review describes the product of the 3-day International Association for the Study of Obesity (IASO) Stock Conference held in March 2004 and sponsored by Abbott Laboratories. The conference was focused on how the mechanisms by which individual cells sense their own fuel status might influence the energy balance of the entire organism. Whether you are a single-celled organism or a sophisticated mammal with a large cerebral cortex, it is critical that cellular activity be matched to the available fuel necessary for that activity. Rapid progress has been made in the last decade in our understanding of the critical metabolic events that cells monitor to accomplish this critical task. More recent developments have begun to apply this understanding to how critical populations of neurones may monitor similar events to control both food intake and energy expenditure. The picture that emerges is that numerous peripheral fuel sensors communicate to the central nervous system (CNS) via neural and humoral routes. Moreover, it has been known for decades that specific populations of neurones sense changes in ambient glucose levels and adjust their firing rate in response and changes in neuronal glucose metabolism can influence energy balance. The CNS, however, does not just sense glucose but rather appears to be sensitive to a wide range of metabolic perturbations associated with fuel availability. This information is used to adjust both caloric intake and the disposition of fuels in the periphery. Increased understanding of these CNS fuel-sensing mechanisms may lead to novel therapeutic targets for obesity.