Nutrition Research Reviews

Review Article

Peripheral and central mechanisms involved in the control of food intake by dietary amino acids and proteins

Gilles Fromentina1a2 c1, Nicolas Darcela2a3, Catherine Chaumonteta1a2, Agnes Marsset-Baglieria1a2, Nachiket Nadkarnia3 and Daniel Toméa1a2

a1 INRA, CNRH-IdF, UMR914 Nutrition Physiology and Ingestive Behaviour, F-75005 Paris, France

a2 AgroParisTech, CNRH-IdF, UMR914 Nutrition Physiology and Ingestive Behaviour, F-75005 Paris, France

a3 Chaire ANCA, F-75005 Paris, France


The present review summarises current knowledge and recent findings on the modulation of appetite by dietary protein, via both peripheral and central mechanisms. Of the three macronutrients, proteins are recognised as the strongest inhibitor of food intake. The well-recognised poor palatability of proteins is not the principal mechanism explaining the decrease in high-protein (HP) diet intake. Consumption of a HP diet does not induce conditioned food aversion, but rather experience-enhanced satiety. Amino acid consumption is detected by multiple and redundant mechanisms originating from visceral (during digestion) and metabolic (inter-prandial period) sources, recorded both directly and indirectly (mainly vagus-mediated) by the central nervous system (CNS). Peripherally, the satiating effect of dietary proteins appears to be mediated by anorexigenic gut peptides, principally cholecystokinin, glucagon-like peptide-1 and peptide YY. In the CNS, HP diets trigger the activation of noradrenergic and adrenergic neurons in the nucleus of the solitary tract and melanocortin neurons in the arcuate nucleus. Additionally, there is evidence that circulating leucine levels may modulate food intake. Leucine is associated with neural mechanisms involving mammalian target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK), energy sensors active in the control of energy intake, at least in the arcuate nucleus of the hypothalamus. In addition, HP diets inhibit the activation of opioid and GABAergic neurons in the nucleus accumbens, and thus inhibit food intake by reducing the hedonic response to food, presumably because of their low palatability. Future studies should concentrate on studying the adaptation of different neural circuits following the ingestion of protein diets.


c1 Corresponding author: Dr Gilles Fromentin, fax +33 1 44 08 18 58, email


Abbreviations: AgRP, Agouti-related peptide; AMPK, AMP-activated protein kinase; ARC, arcuate nucleus of the hypothalamus; CCK, cholecystokinin; GLP-1, glucagon-like peptide-1; HP, high protein; mTOR, mammalian target of rapamycin; NP, normal protein; NPY, neuropeptide Y; NTS, nucleus of the solitary tract; POMC, pro-opiomelanocortin; PYY, peptide YY