Model for the regulation of energy balance and adiposity by the central nervous system

This review integrates new information into a revised model of energy homeostasis that proposes that long-term adiposity-related signals such as insulin and leptin influence the neuronal activity of central effector pathways that serve as controllers of energy balance.

Abstract

We describe a new model for adiposity regulation in which two distinct classes of peripheral afferent signals modulate neuronal pathways in the brain that control meal initiation, meal termination, and the autonomic outflow influencing the fate of ingested energy. These brain pathways, termed central-effector pathways for the control of energy balance, respond to 1) short-term, situational-, and meal-related signals that are crucial to the size and timing of individual meals, but that are not components of the system serving to regulate adipose stores, and 2) long-term, adiposity-related signals that participate in the negative feedback control of fat stores. Long-term signals, such as the pancreatic hormone insulin, are secreted into the circulation in proportion to energy balance and adipose mass. These signals enter the brain where they influence central-effector pathways, in part by changing the sensitivity of these pathways to short-term signals. Through this mechanism, the central nervous system response to short-term signals is adjusted in proportion to changes in body adiposity, resulting in compensatory changes in food intake and energy expenditure that collectively favor the long-term stability of fat stores. This model provides a comprehensive framework for experimental design and data interpretation in the study of body adiposity regulation.