Metabolic and hedonic drives in the neural control of appetite: who is the boss?
Highlights
► Energy balance is normally tightly regulated by feedback signals from ingested and stored nutrients. ► In our modern world, cognitive and emotional factors can overpower energy balance regulation. ► Cognition and emotions can in turn be modulated by signals of nutrient availability. ► Understanding the rules of interaction will help find new therapies to prevent or reverse obesity.
Introduction
In our modern world, we no longer eat only when metabolically hungry. We often eat in the complete absence of hunger and in spite of large fat reserves. Eating when fuels are depleted and abstaining from eating when replete serves a ‘homeostatic’ model for the regulation of energy balance. In contrast to this metabolically driven eating, all other eating can be considered ‘nonhomeostatic’, implying that it is not regulated or compensated by some form of metabolic feedback. A more expressive term for ‘nonhomeostatic’ is ‘hedonic’ eating, which refers to the involvement of cognitive, reward, and emotional factors. Much progress has been made in identifying the metabolic feedback signals and neural systems, located mainly in brainstem and hypothalamus, that represent a ‘homeostatic regulator’ (Figure 1). On the other hand, the neural pathways and functions principally located in cortico-limbic structures responsible for ‘hedonic’ eating — eating that has parallels with addiction mechanisms — are much less understood. Importantly, it is necessary to understand how these metabolic and hedonic pathways interact with each other. The following is an attempt to delineate these potential pathways and mechanisms of such interaction by reviewing recent evidence.
Section snippets
Bottom-up processes: metabolic signals modulate higher brain functions
It has long been known that food deprivation or restriction increases the reinforcement value of a food reward [1]. This basic observation has been confirmed in numerous studies, and modern neuroimaging techniques have begun to identify the specific neural systems involved in humans. A recent study in fasting healthy human subjects viewing pictures of high-calorie versus low-calorie foods showed that high-calorie foods selectively increased neural activity in reward related areas such as the
Top-down processes: reward and cognitive functions modulate metabolic state
Top-down processes include neural signals that influence peripheral metabolism and/or the brain systems important in regulating energy state, and the recent obesity epidemic makes clear that ‘homeostatic’ body weight regulatory processes can be overridden by other influences. This idea is supported by a recent study of overfed rats, which showed an orexigenic basomedial hypothalamic peptide expression profile that should signal for reduced energy intake. Yet despite increased expression of
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Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
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