Neuro-metabolic pathways of high-protein meal reducing food craving

ABSTRACT Across species, high-protein foods have been shown to reduce appetite throughout the day. Although higher protein intake alters multiple metabolic responses, the exact neuro-metabolic mechanisms underlying food craving remain unclear. Here, we investigated whether a protein-rich diet modulates plasma tyrosine dynamics, the precursor of dopamine, thereby altering dopaminergic brain activity and reducing food craving in humans. In this within-subject, cross-over study, 30 healthy participants (age, 23.63 ±3.23 years) were provided with either a high- or low-protein/carbohydrate breakfast. Three and a half hours after breakfast, participants viewed high-or low caloric food images while undergoing magnetic resonance imaging (MRI), and their subjective food craving was assessed using the validated Food Craving Questionnaire- State version. Through the experimental procedure, plasma tyrosine levels were continuously monitored. Our results show that the high-protein/carbohydrate breakfast significantly enhanced plasma tyrosine levels, which were negatively associated with subjective food craving several hours after meal intake. Importantly, we observed significantly stronger midbrain activity following the high-protein/carbohydrate breakfast, which was associated with greater reduction in subjective food craving. Furthermore, we analyzed brain gradients that characterize spatial patterns of large-scale neural activity, allowing us to examine the entire process underlying dietary choices at the whole-brain level. Compared with the low-protein/carbohydrate breakfast, the high-protein/carbohydrate breakfast reduced whole-brain functional reorganization, indicating lower neural sensitivity to high- versus low-caloric food stimuli. Notably, the degree of this high-protein/carbohydrate induced brain-state shift was related to the reduction in food craving. Together, these results provide strong evidence that high-protein/carbohydrate meals modulate dopaminergic mechanisms and large-scale whole-brain neural reorganization, contributing to reduced food craving throughout the day in humans. Graphic Abstract High-protein/carbohydrate breakfast significantly enhanced plasma tyrosine levels, which were negatively associated with subjective food craving over several hours. High-protein/carbohydrate breakfast recruited significantly stronger midbrain activity, which was associated with a greater reduction in subjective food craving. High-protein/carbohydrate breakfast regulated whole-brain functional reorganization, leading to dampened neural sensitivity to high-caloric food stimuli, and consequently lower food craving.