Re-examination of Dietary Amino Acid Sensing Reveals a GCN2-Independent Mechanism

Animals cannot synthesize nine essential amino acids (EAAs) and must therefore obtain them from food. Mice reportedly reject food lacking a single EAA within the first hour of feeding. This remarkable phenomenon is proposed to involve post-ingestive sensing of amino acid imbalance by the protein kinase GCN2 in the brain. Here, we systematically re-examine dietary amino acid sensing in mice. In contrast to previous results, we find that mice cannot rapidly identify threonine- or leucine-deficient food in common feeding paradigms. However, mice attain the ability to identify EAA-deficient food following 2 days of EAA deprivation, suggesting a requirement for physiologic need. In addition, we report that mice can rapidly identify lysine-deficient food without prior EAA deficit, revealing a distinct sensing mechanism for this amino acid. These behaviors are independent of the proposed amino acid sensor GCN2, pointing to the existence of an undescribed mechanism for rapid sensing of dietary EAAs. [Display omitted] •Mice do not reject food lacking essential amino acids (EAA) as previously reported•The proposed EAA sensor GCN2 is not activated in the brain by EAA-deficient food•Mice attain the ability to identify EAA deficit food following EAA deprivation•Dietary EAA sensing depends on physiologic need, but not GCN2 Leib and Knight reinvestigate how animals sense the amino acid content of food. Contrary to earlier reports, they show that mice can rapidly identify food lacking an essential amino acid (EAA) only if they have previously been EAA deprived. Furthermore, this need-based mechanism does not require the proposed sensor GCN2.