Mice but not rats modulate liver mitochondrial machinery in chronic hypoxia
Bibliographic record
Abstract
Mice (FVB) permanently living at high‐altitude have increased respiratory frequencies and sustained or increased metabolic rates. On the other hand, rats permanently living at high‐altitude (SD) have impaired respiratory control, high hematocrit and hemoglobin, signs of pulmonary hypertension, and reduced metabolism; all these considered to be detrimental. This is coincident with the fact that common rats are not found in natural high‐altitude environments. At sea level, we reported that mice, but nor rats, exposed to 21 days of hypoxia (12% O2) increase their metabolic rate (O 2 consumption and CO 2 production), similarly to other rodent species that are considered well adapted to high‐altitude. As mitochondria is the final user of O 2 in metabolism, we were interested in the role of mitochondria behind this divergence in physiological adjustments. We used saponin‐permeabilized samples of liver (most energy‐consuming organ in rodents), 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) following the SUIT‐01 protocol in the high‐resolution respirometer O2K (OROBOROS instruments). OCR was measured with substrates activating the NADH, succinate , and fatty acid pathways of the electron transport chain (ETC). We also measured the maximum capacity of ETC by uncoupling the electron transport from the oxidative phosphorylation with CCCP. The level of activation of complexes I and II was reported as the OCR for the N or S pathway correspondingly, divided by the maximum capacity (flux control ratio). Our preliminary results show that, compared to rats, mice have significantly higher ETC maximum capacities in normoxia and hypoxia. Moreover, after 21 days of hypoxia, mice showed an increase of 43% in maximum capacity in comparison to normoxic controls, while no increase in maximum capacity was evidenced in rats. In mice, we observed that complex I is transiently hyperactivated after 1 day of hypoxia and then, its activity reduces down below control levels by day 21 of hypoxia. Contrastingly, complex II activity is reduced after one day of hypoxia, getting back to control levels by day 21 of hypoxia. Furthermore, in rats, an increased activity of complex I occurred after 21 days of hypoxia. Regardless of normoxic or hypoxic exposure, rats showed higher activation levels of complex II than mice. These results show that mice, but not rats, have the ability to modulate their liver metabolic mitochondrial machinery under chronic hypoxia. The higher and adjustable maximum capacity in mice, suggest a more powerful and plastic liver mitochondrial machinery than in rats. This might explain in part their ability to keep sustained metabolic rates under hypoxic conditions. Support or Funding Information Supported by NSERC, the Health Respiratory Network of Québec and CIHR.
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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 | 0.001 |
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".