Neural and metabolic regulation of macronutrient intake and selection

Abstract

There is considerable disagreement regarding what constitutes a healthy diet. Ever since the influential work of Cannon and Richter, it was debated whether the 'wisdom of the body' will automatically direct us to the foods we need for healthy lives or whether we must carefully learn to eat the right foods, particularly in an environment of plenty. Although it is clear that strong mechanisms have evolved to prevent consumption of foods that have previously made us sick, it is less clear whether reciprocal mechanisms exist that reinforce the consumption of healthy diets. Here, we review recent progress in providing behavioural evidence for the regulation of intake and selection of proteins, carbohydrates and fats. We examine new developments in sensory physiology enabling recognition of macronutrients both pre- and post-ingestively. Finally, we propose a general model for central neural processing of nutrient-specific appetites. We suggest that the same basic neural circuitry responsible for the homoeostatic regulation of total energy intake is also used to control consumption of specific macro- and micronutrients. Similar to salt appetite, specific appetites for other micro- and macronutrients may be encoded by unique molecular changes in the hypothalamus. Gratification of such specific appetites is then accomplished by engaging the brain motivational system to assign the highest reward prediction to exteroceptive cues previously associated with consuming the missing ingredient. A better understanding of these nutrient-specific neural processes could help design drugs and behavioural strategies that promote healthier eating.

Fig. 1

Schematic flow diagram showing possible neural processing of external and internal food cues leading to nutrient-specific appetites. Representations of experience with a particular food (food memories) take into account (a) exteroceptive cues including taste, available before ingestion of significant amounts, (b) post-ingestive consequences elicited by ingesting the food (digestion, absorption and metabolism), and (c) the prevailing deprivation state for the particular nutrient at the time of replenishment. The hypothalamic energy sensor may be involved in generating a general hunger signal (incentive), and the cortico-limbic, reward-based decision-making circuitry may confer the behavioural specificity for the selection process. Amy, amygdala; Hipp, hippocampal complex; NAcb, nucleus accumbens; OFC, orbitofrontal cortex; PFC, prefrontral cortex; VTA, ventral tegmental area.