An expanded view of energy homeostasis: neural integration of metabolic, cognitive, and emotional drives to eat

Abstract

The traditional view of neural regulation of body energy homeostasis focuses on internal feedback signals integrated in the hypothalamus and brainstem and in turn leading to balanced activation of behavioral, autonomic, and endocrine effector pathways leading to changes in food intake and energy expenditure. Recent observations have demonstrated that many of these internal signals encoding energy status have much wider effects on the brain, particularly sensory and cortico-limbic systems that process information from the outside world by detecting and interpreting food cues, forming, storing, and recalling representations of experience with food, and assigning hedonic and motivational value to conditioned and unconditioned food stimuli. Thus, part of the metabolic feedback from the internal milieu regulates food intake and energy balance by acting on extrahypothalamic structures, leading to an expanded view of neural control of energy homeostasis taking into account the need to adapt to changing conditions in the environment. The realization that metabolic signals act directly on these non-traditional targets of body energy homeostasis brings opportunities for novel drug targets for the fight against obesity and eating disorders.

Fig. 1

Highly schematic diagram showing neural systems and flow of information involved in the control of food intake and regulation of energy balance. The traditional regulatory circuitry using neural and hormonal feedback from the internal milieu acting on hypothalamus and brainstem is shown on the bottom (dark grey boxes). Sensory and cortico-limbic brain areas used for processing information from the environment are shown in the upper half (light gray boxes). The extensive influence of circulating and neural internal feedback signals on sensory processing and cortico-limbic systems concerned with reward, emotion, learning and memory is emphasized (broken line open arrows).