Protein, amino acids, vagus nerve signaling, and the brain

Am J Clin Nutr. 2009 Sep;90(3):838S-843S. doi: 10.3945/ajcn.2009.27462W. Epub 2009 Jul 29.


Dietary protein and amino acids, including glutamate, generate signals involved in the control of gastric and intestinal motility, pancreatic secretion, and food intake. They include postprandial meal-induced visceral and metabolic signals and associated nutrients (eg, amino acids and glucose), gut neuropeptides, and hormonal signals. Protein reduces gastric motility and stimulates pancreatic secretions. Protein and amino acids are also more potent than carbohydrate and fat in inducing short-term satiety in animals and humans. High-protein diets lead to activation of the noradrenergic-adrenergic neuronal pathway in the brainstem nucleus of the solitary tract and in melanocortin neurons of the hypothalamic arcuate nucleus. Moreover, some evidence indicates that circulating concentrations of certain amino acids could influence food intake. Leucine modulates the activity of energy and nutrient sensor pathways controlled by AMP-activated protein kinase and mammalian target of rapamycin in the hypothalamus. At the brain level, 2 afferent pathways are involved in protein and amino acid monitoring: the indirect neural (mainly vagus-mediated) and the direct humoral pathways. The neural pathways transfer preabsorptive and visceral information through the vagus nerve that innervates part of the orosensory zone (stomach, duodenum, and liver). Localized in the brainstem, the nucleus of the solitary tract is the main projection site of the vagus nerve and integrates sensory information of oropharyngeal, intestinal, and visceral origins. Ingestion of protein also activates satiety pathways in the arcuate nucleus, which is characterized by an up-regulation of the melanocortin pathway (alpha-melanocyte-stimulating, hormone-containing neurons) and a down-regulation of the neuropeptide Y pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / pharmacology*
  • Brain / drug effects*
  • Brain / physiology
  • Dietary Proteins / pharmacology*
  • Humans
  • Signal Transduction / drug effects*
  • Signal Transduction / physiology
  • Vagus Nerve / drug effects*
  • Vagus Nerve / physiology


  • Amino Acids
  • Dietary Proteins