Triggering mitochondrial plasticity in the liver of rodents is key for successful acclimatization to hypoxia
Bibliographic record
Abstract
Liver is the most metabolically active organ in mice and rats, accounting for up to 50% of the body's energy expenditure. As such, this organ is highly sensitive to the reduction in O 2 availability occurring in hypoxic conditions such as high‐altitude. Keeping in mind that mice, but not rats, successfully colonized habitats over 2,500 masl, we showed previously that mice only increase their metabolic rates under chronic hypoxia. Accordingly, we hypothesized here that mice and rats have divergent mitochondrial and molecular features in the liver that determine an adequate energy balance in mice (not rats) during the process of acclimatization to hypoxia. To test this hypothesis, we used saponin‐permeabilized samples of liver from male adult FVB mice and SD rats after exposure to hypoxia (12% O 2 , for 0, 1, 7 or 21 days) to measure the mitochondrial O 2 consumption rate (OCR) and the activation of the N (complex I‐linked), S (complex II‐linked), and NS (complex I&II‐linked) electron‐transfer pathways in the high‐resolution respirometer O2K (OROBOROS instruments). Additional experiments were performed to evaluate the activity of representative enzymes from the glycolytic (hexokinase [HK]), aerobic (pyruvate dehydrogenase [PDH]), and anaerobic (lactate dehydrogenase [LDH]) metabolic pathways by spectrometric methods. Our results show that liver mitochondria in mice increase the OCR and improve the activation of the electron‐transfer pathways S (complex II‐linked) and NS (complexes I&II‐linked). in line, the glycolytic and aerobic metabolic enzymatic activities (HK and PDH) increased, while the anaerobic metabolism (LDH) reduced after seven‐days hypoxia. On the other hand, rats were shown to be unable of altering liver mitochondrial respiration but augmented glycolytic and anaerobic metabolic activities (HK and LDH) and concomitantly reduced the aerobic metabolism (PDH). These results show that liver mitochondria of mice display plastic responses in the utilization of oxygen during the process of acclimatization to hypoxia and that these changes are supported by adjustments in the glycolytic, aerobic, and anaerobic metabolic pathways. Contrastingly, together with the inability to adjust their mitochondrial activity, rats depend heavily on anaerobic pathways (known to be less effective) to produce energy. Our results contribute to explain why mice, but not rats, are present in high‐altitude environments.
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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) | 0.002 | 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".