Protein-dependent regulation of feeding and metabolism

Abstract

Free-feeding animals often face complex nutritional choices that require the balancing of competing nutrients, but the mechanisms driving macronutrient-specific food intake are poorly defined. A large number of behavioral studies indicate that both the quantity and quality of dietary protein can markedly influence food intake and metabolism, and that dietary protein intake may be prioritized over energy intake. This review focuses on recent progress in defining the mechanisms underlying protein-specific feeding. Considering the evidence that protein powerfully regulates both food intake and metabolism, uncovering these protein-specific mechanisms may reveal new molecular targets for the treatment of obesity and diabetes while also offering a more complete understanding of how dietary factors shape both food intake and food choice.

Keywords: FGF21; GCN2; amino acids; dietary protein; leucine; macronutrient.

Figure 1. Mechanisms through which changes in dietary protein intake are detected and communicated to the brain

Dietary protein within the GI tract activates both endocrine and vagal signals, which act in a primarily anorexigenic fashion in the hypothalamus and brainstem. Absorbed amino acids are delivered to the liver via the hepatic portal vein. Reduced amino acid supply to the liver increases hepatic FGF21 secretion, which acts in the brain to increase both food intake and energy expenditure, likely via effects in the hypothalamus. Amino acids are transported out of the liver and into the general circulation, and circulating amino acids can act in both the hypothalamus and brainstem to suppress food intake. Finally, imbalances in dietary or circulating amino acid concentrations are detected in the anterior piriform cortex (APC), with activation of the APC reducing food intake. These various mechanisms allow animals to detect and adaptively respond to diets that are high, low or imbalanced in amino acid content.