Metabolic and hedonic drives in the neural control of appetite: who is the boss?

Abstract

Obesity is on the rise in all developed countries, and a large part of this epidemic has been attributed to excess caloric intake, induced by ever present food cues and the easy availability of energy dense foods in an environment of plenty. Clearly, there are strong homeostatic regulatory mechanisms keeping body weight of many individuals exposed to this environment remarkably stable over their adult life. Other individuals, however, seem to eat not only because of metabolic need, but also because of excessive hedonic drive to make them feel better and relieve stress. In the extreme, some individuals exhibit addiction-like behavior toward food, and parallels have been drawn to drug and alcohol addiction. However, there is an important distinction in that, unlike drugs and alcohol, food is a daily necessity. Considerable advances have been made recently in the identification of neural circuits that represent the interface between the metabolic and hedonic drives of eating. We will cover these new findings by focusing first on the capacity of metabolic signals to modulate processing of cognitive and reward functions in cortico-limbic systems (bottom-up) and then on pathways by which the cognitive and emotional brain may override homeostatic regulation (top-down).

Fig. 1

Schematic diagram showing the major factors determining neural control of appetite and regulation of energy balance. The brain monitors the internal milieu through a number of hormonal and neural nutrient sensing mechanisms and is under constant influence of the environment and lifestyle through the senses and mainly the cognitive and emotional brain. The two streams of information are integrated to generate adaptive behavioral (food intake) and autonomic/endocrine responsses determining nutrient partitioning, energy expenditure, and overall energy balance. All of the peripheral and central signaling steps are subject to individual predisposition either through genetic, epigenetic, or non-genetic early life imprinting mechanisms.

Fig. 2

Schematic diagram showing potential interactions between the so called “homeostatic” energy balance regulatory system (blue) and neural systems involved in external sensory information processing (yellowish-brown), reward processing (purple), and cognition and executive functions (red), collectively referred to as “hedonic systems”. Blue arrows indicate bottom-up modulation of hedonic systems by homeostatic signals. Broken blue lines represent circulating hormones, metabolites, and other factors; solid blue lines represent neural pathways. Red arrows indicate top-down modulation of homeostatic processes by hedonic drives. See text for discussion of specific interactive pathways.