5′‐AMP activated protein kinase α<sub>2</sub> controls substrate metabolism during post‐exercise recovery via regulation of pyruvate dehydrogenase kinase 4
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Bibliographic record
Abstract
Key points There is lower fat oxidation during post‐exercise recovery in mice lacking 5′‐AMP activated protein kinase α 2 (AMPKα 2 ). AMPKα 2 is involved in post‐transcriptional and not transcriptional regulation of pyruvate dehydrogenase kinase 4 (PDK4) in muscle. Exercise‐induced AMPKα 2 activity increases PDK4 protein content, in turn inhibiting pyruvate dehydrogenase activity and glucose oxidation. The mechanism for increased post‐exercise fat oxidation is by inhibition of carbohydrate oxidation allowing increased fat oxidation rather than by direct stimulation of fat oxidation. Abstract It is well known that exercise has a major impact on substrate metabolism for many hours after exercise. However, the regulatory mechanisms increasing lipid oxidation and facilitating glycogen resynthesis in the post‐exercise period are unknown. To address this, substrate oxidation was measured after prolonged exercise and during the following 6 h post‐exercise in 5´‐AMP activated protein kinase (AMPK) α 2 and α 1 knock‐out (KO) and wild‐type (WT) mice with free access to food. Substrate oxidation was similar during exercise at the same relative intensity between genotypes. During post‐exercise recovery, a lower lipid oxidation ( P < 0.05) and higher glucose oxidation were observed in AMPKα 2 KO (respiratory exchange ratio (RER) = 0.84 ± 0.02) than in WT and AMPKα 1 KO (average RER = 0.80 ± 0.01) without genotype differences in muscle malonyl‐CoA or free‐carnitine concentrations. A similar increase in muscle pyruvate dehydrogenase kinase 4 (PDK4) mRNA expression in WT and AMPKα 2 KO was observed following exercise, which is consistent with AMPKα 2 deficiency not affecting the exercise‐induced activation of the PDK4 transcriptional regulators HDAC4 and SIRT1. Interestingly, PDK4 protein content increased (63%, P < 0.001) in WT but remained unchanged in AMPKα 2 KO. In accordance with the lack of increase in PDK4 protein content, lower ( P < 0.01) inhibitory pyruvate dehydrogenase (PDH)‐E1α Ser 293 phosphorylation was observed in AMPKα 2 KO muscle compared to WT. These findings indicate that AMPKα 2 regulates muscle metabolism post‐exercise through inhibition of the PDH complex and hence glucose oxidation, subsequently creating conditions for increased fatty acid oxidation.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it