Regulation of muscle pyruvate dehydrogenase activity and fuel use during exercise in high-altitude deer mice
Bibliographic record
Abstract
Adult, lab-reared, highland deer mice acclimate to hypoxia by increasing reliance on carbohydrates to fuel exercise. Yet neither the underlying mechanisms for this shift in fuel use nor the impact of lifetime hypoxia exposure experienced in high alpine conditions, are fully understood. Thus, we assessed the use of fuel during exercise in wild highland deer mice running in their native environment. We examined a key step in muscle carbohydrate oxidation - the regulation of pyruvate dehydrogenase (PDH) - during exercise at altitude in wild highlanders and in first generation (G1) lab-born and -raised highlanders acclimated to normoxia or hypoxia. PDH activity was also determined in the gastrocnemius of G1 highlanders using an in situ muscle preparation. We found that wild highlanders had a high reliance on carbohydrates while running in their native environment, consistent with data from hypoxia-acclimated G1 highlanders. PDH activity in the gastrocnemius was similar post exercise between G1 and wild highlanders. However, when the gastrocnemius was stimulated at a light work rate in situ, PDH activity was higher in hypoxia-acclimated G1 highlanders and was associated with lower intramuscular lactate levels. These findings were supported by lower PDH kinase 2 protein production in hypoxia-acclimated G1 mice. Our findings indicate that adult phenotypic plasticity in response to low oxygen is sufficient to increase carbohydrate reliance during exercise in highland deer mice. Additionally, variation in PDH regulation with hypoxia acclimation contributes to shifts in whole-animal patterns of fuel use and is likely to improve exercise performance via elevated energy yield per mole of O2. .
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".