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

Leib DE, Knight ZA - Cell Rep (2015)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, University of California, San Francisco, San Francisco, CA 94158, USA.

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Mice Do Not Sense Dietary EAA Deficiency within the First 3 hr of Feeding(A) Feeding paradigm controlling for dietary novelty used in (B)–(G). Consumption of the novel control and test diets was quantified as a percentage of food consumed overnight on the previous night.(B) Wild-type (n = 5) and Gcn2−/− (n = 5) mice did not consume a significantly different amount of T-def than novel control in the first 3 hr of feeding. Overnight, mice consumed significantly less T-def food than novel control (p = 0.005), and Gcn2−/− consumed more food overall than wild-type (p = 0.04), but there was no interaction between diet and genotype.(C) Wild-type mice (n = 7) did not consume a significantly different amount of L-def food than novel control in the first 3 hr of feeding. Overnight, the mice consumed significantly less L-def food than novel control (p = 0.007).(D) Wild-type mice (n = 9) did not consume a significantly different amount of TL-def food than novel control in the first 3 hr of feeding. Overnight, the mice consumed significantly less TL-def food than novel control (p = 0.0008).(E) Wild-type mice (n = 5) did not consume a significantly different amount of K-def food compared to novel control in the first 3 hr of feeding or overnight.(F) Wild-type (n = 7) and Gcn2−/− (n = 5) mice consumed significantly less AA-dev food than novel control in the first 3 hr of feeding (p = 0.0009) and overnight (p < 0.0001), with no significant effects of genotype or interaction between diet and genotype.(G) Wild-type (n = 6) and Gcn2−/− (n = 6) mice pre-fed L-basal food did not consume a significantly different amount of L-def food compared to novel control in the first 3 hr of feeding or overnight.(H) Behavioral paradigm for fasting and refeeding experiment in (I).(I) Wild-type (n = 14) and Gcn2−/− (n = 6) mice did not consume a significantly different amount of TL-def food compared to novel control in the first 3 hr of feeding following a 27-hr fast. Overnight, the mice consumed significantly less TL-def food than novel control (p < 0.0001), with no significant effects of genotype or interaction between diet and genotype.See also Figures S1 and S2.
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Figure 1: Mice Do Not Sense Dietary EAA Deficiency within the First 3 hr of Feeding(A) Feeding paradigm controlling for dietary novelty used in (B)–(G). Consumption of the novel control and test diets was quantified as a percentage of food consumed overnight on the previous night.(B) Wild-type (n = 5) and Gcn2−/− (n = 5) mice did not consume a significantly different amount of T-def than novel control in the first 3 hr of feeding. Overnight, mice consumed significantly less T-def food than novel control (p = 0.005), and Gcn2−/− consumed more food overall than wild-type (p = 0.04), but there was no interaction between diet and genotype.(C) Wild-type mice (n = 7) did not consume a significantly different amount of L-def food than novel control in the first 3 hr of feeding. Overnight, the mice consumed significantly less L-def food than novel control (p = 0.007).(D) Wild-type mice (n = 9) did not consume a significantly different amount of TL-def food than novel control in the first 3 hr of feeding. Overnight, the mice consumed significantly less TL-def food than novel control (p = 0.0008).(E) Wild-type mice (n = 5) did not consume a significantly different amount of K-def food compared to novel control in the first 3 hr of feeding or overnight.(F) Wild-type (n = 7) and Gcn2−/− (n = 5) mice consumed significantly less AA-dev food than novel control in the first 3 hr of feeding (p = 0.0009) and overnight (p < 0.0001), with no significant effects of genotype or interaction between diet and genotype.(G) Wild-type (n = 6) and Gcn2−/− (n = 6) mice pre-fed L-basal food did not consume a significantly different amount of L-def food compared to novel control in the first 3 hr of feeding or overnight.(H) Behavioral paradigm for fasting and refeeding experiment in (I).(I) Wild-type (n = 14) and Gcn2−/− (n = 6) mice did not consume a significantly different amount of TL-def food compared to novel control in the first 3 hr of feeding following a 27-hr fast. Overnight, the mice consumed significantly less TL-def food than novel control (p < 0.0001), with no significant effects of genotype or interaction between diet and genotype.See also Figures S1 and S2.

Mentions: We first attempted to replicate the result that mice consume less threonine-deficient (T-def) or leucine-deficient (L-def) food than control food in the first 1–3 hr of feeding. Test diets were synthesized that lacked one or more amino acids (Table S1) and used in a behavioral assay that compared intake of the test diet and control diet on different days in a randomized order (Figure 1A). Importantly, the test and control diets used in this paradigm were both novel, which ensures that differences in food intake reflect true dietary preferences and not neophobia (Corey, 1978).


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

Leib DE, Knight ZA - Cell Rep (2015)

Mice Do Not Sense Dietary EAA Deficiency within the First 3 hr of Feeding(A) Feeding paradigm controlling for dietary novelty used in (B)–(G). Consumption of the novel control and test diets was quantified as a percentage of food consumed overnight on the previous night.(B) Wild-type (n = 5) and Gcn2−/− (n = 5) mice did not consume a significantly different amount of T-def than novel control in the first 3 hr of feeding. Overnight, mice consumed significantly less T-def food than novel control (p = 0.005), and Gcn2−/− consumed more food overall than wild-type (p = 0.04), but there was no interaction between diet and genotype.(C) Wild-type mice (n = 7) did not consume a significantly different amount of L-def food than novel control in the first 3 hr of feeding. Overnight, the mice consumed significantly less L-def food than novel control (p = 0.007).(D) Wild-type mice (n = 9) did not consume a significantly different amount of TL-def food than novel control in the first 3 hr of feeding. Overnight, the mice consumed significantly less TL-def food than novel control (p = 0.0008).(E) Wild-type mice (n = 5) did not consume a significantly different amount of K-def food compared to novel control in the first 3 hr of feeding or overnight.(F) Wild-type (n = 7) and Gcn2−/− (n = 5) mice consumed significantly less AA-dev food than novel control in the first 3 hr of feeding (p = 0.0009) and overnight (p < 0.0001), with no significant effects of genotype or interaction between diet and genotype.(G) Wild-type (n = 6) and Gcn2−/− (n = 6) mice pre-fed L-basal food did not consume a significantly different amount of L-def food compared to novel control in the first 3 hr of feeding or overnight.(H) Behavioral paradigm for fasting and refeeding experiment in (I).(I) Wild-type (n = 14) and Gcn2−/− (n = 6) mice did not consume a significantly different amount of TL-def food compared to novel control in the first 3 hr of feeding following a 27-hr fast. Overnight, the mice consumed significantly less TL-def food than novel control (p < 0.0001), with no significant effects of genotype or interaction between diet and genotype.See also Figures S1 and S2.
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Figure 1: Mice Do Not Sense Dietary EAA Deficiency within the First 3 hr of Feeding(A) Feeding paradigm controlling for dietary novelty used in (B)–(G). Consumption of the novel control and test diets was quantified as a percentage of food consumed overnight on the previous night.(B) Wild-type (n = 5) and Gcn2−/− (n = 5) mice did not consume a significantly different amount of T-def than novel control in the first 3 hr of feeding. Overnight, mice consumed significantly less T-def food than novel control (p = 0.005), and Gcn2−/− consumed more food overall than wild-type (p = 0.04), but there was no interaction between diet and genotype.(C) Wild-type mice (n = 7) did not consume a significantly different amount of L-def food than novel control in the first 3 hr of feeding. Overnight, the mice consumed significantly less L-def food than novel control (p = 0.007).(D) Wild-type mice (n = 9) did not consume a significantly different amount of TL-def food than novel control in the first 3 hr of feeding. Overnight, the mice consumed significantly less TL-def food than novel control (p = 0.0008).(E) Wild-type mice (n = 5) did not consume a significantly different amount of K-def food compared to novel control in the first 3 hr of feeding or overnight.(F) Wild-type (n = 7) and Gcn2−/− (n = 5) mice consumed significantly less AA-dev food than novel control in the first 3 hr of feeding (p = 0.0009) and overnight (p < 0.0001), with no significant effects of genotype or interaction between diet and genotype.(G) Wild-type (n = 6) and Gcn2−/− (n = 6) mice pre-fed L-basal food did not consume a significantly different amount of L-def food compared to novel control in the first 3 hr of feeding or overnight.(H) Behavioral paradigm for fasting and refeeding experiment in (I).(I) Wild-type (n = 14) and Gcn2−/− (n = 6) mice did not consume a significantly different amount of TL-def food compared to novel control in the first 3 hr of feeding following a 27-hr fast. Overnight, the mice consumed significantly less TL-def food than novel control (p < 0.0001), with no significant effects of genotype or interaction between diet and genotype.See also Figures S1 and S2.
Mentions: We first attempted to replicate the result that mice consume less threonine-deficient (T-def) or leucine-deficient (L-def) food than control food in the first 1–3 hr of feeding. Test diets were synthesized that lacked one or more amino acids (Table S1) and used in a behavioral assay that compared intake of the test diet and control diet on different days in a randomized order (Figure 1A). Importantly, the test and control diets used in this paradigm were both novel, which ensures that differences in food intake reflect true dietary preferences and not neophobia (Corey, 1978).

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, University of California, San Francisco, San Francisco, CA 94158, USA.

Show MeSH
Related in: MedlinePlus