title: Re-examination of Dietary Amino Acid Sensing Reveals a GCN2-Independent Mechanism.
abstract: 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.
authors.affiliation: Department of Physiology, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Leib
authors.affiliation: Department of Physiology, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: zachary.knight@ucsf.edu.
authors.forename: Zachary A
authors.initials: ZA
authors.lastname: Knight
mesh_terms: D000601:Amino Acids, Essential / Q000172:deficiency / Q000378:metabolism*; D000818:Animals; D004044:Dietary Proteins / Q000378:metabolism*; D005518:Food Preferences; D051379:Mice; D008810:Mice, Inbred C57BL; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012677:Sensation / Q000235:genetics*
chemical_list: D000601:Amino Acids, Essential; D004044:Dietary Proteins; C070634:Eif2ak4 protein, mouse; D017346:Protein Serine-Threonine Kinases