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.

Gluttony and guilt: monthly trends in internet search query data are comparable with national-level energy intake and dieting behavior

“…The consistent protein intake is in keeping with evidence suggesting that humans more strongly regulate their intake of protein over non-protein macronutrients (Simpson and Raubenheimer, 2005;Martinez-Cordero et al, 2012;Gosby et al, 2014;Raubenheimer et al, 2016). A variety of animals have been shown to have separate appetite systems for protein, fat, and carbohydrates (Raubenheimer and Simpson, 1997;Berthoud and Seeley, 2000). For those animals, such as humans, in which protein is more strongly regulated than the other macronutrients, low-percent protein diets can drive excess energy intake through increased consumption of surplus non-protein energy to gain limiting protein (the "protein leverage hypothesis"; Simpson and Raubenheimer, 2005).…”

Enhancement of Neural Salty Preference in Obesity

“…Furthermore, the normalized glucose metabolism in these regions was positively correlated with the individual salt intake and salty preference score. Interestingly, the OFC and parahippocampus can retain the food memories that interact with the reward–based decision-making process, which may be involved in food-seeking behaviors [39]. Our results potentially provide physiologic insights indicating that overweight/obesity individuals develop a less adverse reaction to high salt intake and a more hedonic response to salty taste than normal weight individuals.…”

Sex differences in the physiology of eating

“…A distributed network of metabolite-and hormone-sensing neurons in the brain and periphery contributes to energy homeostasis, in part via the control of eating (69,416,427). A relatively small amount of data suggests that there are sex differences in the metabolic control of eating.…”