Re-examination of Dietary Amino Acid Sensing Reveals a GCN2-Independent Mechanism.
Bottom Line: Animals cannot synthesize nine essential amino acids (EAAs) and must therefore obtain them from food.In contrast to previous results, we find that mice cannot rapidly identify threonine- or leucine-deficient food in common feeding paradigms.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.
Affiliation: Department of Physiology, University of California, San Francisco, San Francisco, CA 94158, USA.Show MeSH
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Mentions: As we had failed to find evidence for rapid detection of threonine or leucine deficiency, we considered the possibility that accurate identification of diets lacking these amino acids may require development of a physiologic deficit. In other words, animals might only reject threonine- or leucine-deficient food when they have a specific physiologic need for that amino acid. To test this, we fed mice TL-def food for 2 days to induce threonine/leucine deficiency and then gave them a choice between novel control and TL-def diets (Figure 4A). Strikingly, we found that mice showed a strong preference for control diet over TL-def diet in the first 3 hr of feeding, and this rapid choice did not require GCN2 (wild-type 0.39 ± 0.16 g versus 0.01 ± 0.01 g; Gcn2−/− 0.24 ± 0.07 g versus 0.06 ± 0.04 g; diet, p = 0.01; genotype, p = 0.54; interaction, p = 0.31). This choice was maintained overnight, and in fact, mice did not consume a detectable amount of TL-def food after the first 3 hr of feeding. We repeated this experiment by depriving wild-type mice of threonine for 2 days and then testing T-def and control diets in a choice assay (Figure 4B). All mice robustly chose control over T-def food in the first 3 hr and overnight. Thus, mice do have the ability to rapidly sense dietary threonine and leucine deficiency, but this is only revealed in choice assays following prolonged EAA deprivation.
Affiliation: Department of Physiology, University of California, San Francisco, San Francisco, CA 94158, USA.