Effects of omega-3 supplementation on markers of autophagy, apoptosis and mitochondrial area density
Bibliographic record
Abstract
In humans, disuse is known to result in muscle atrophy and metabolic dysfunction, including reduced mitochondrial content. Previous data from this cohort found that omega-3 polyunsaturated fatty acid (n-3) supplementation attenuated declines in muscle mass, myofibrillar protein synthesis and ADP-stimulated mitochondrial respiration. Disuse has also been shown to increase apoptosis and events linked to autophagy. We investigated the effects of n-3 fatty acid supplementation on content of proteins involved in autophagy, intrinsic apoptosis, mitochondrial fission and fusion and mitochondrial area density during 14 d of immobilization and 14 d of recovery. Twenty females (18-30y) received 20mL doses of n-3 fatty acid (2.97g EPA and 2.03g DHA) or an isoenergetic sunflower oil (oleic acid content: 75%) daily during the 28-d protocol. Biopsies were taken from the vastus lateralis pre-immobilization, post-immobilization, and post-recovery. Protein and mitochondrial content were determined using Western Blot and transmission electron microscopy at 5800X magnification, respectively. Mitochondrial area density (%AD) decreased in the subsarcolemmal (SS, p=0.006) and central intramyofibrillar (IMF) (p=0.001) regions after recovery. The change in the central IMF was driven by a decrease in the n-3 group (p=0.0133). There was no change in the peripheral IMF region. P62 increased during immobilization (p<0.0001) and decreased in recovery (p<0.0001). After immobilization LC3B-I increased in the n-3 group only (p=0.0289). Procaspase-3 content was higher in the n-3 group at all timepoints, D0 (p<0.001), D14 (p<0.0001), D28 (p<0.0001). Procaspase-3 increased after immobilization in the placebo group (p=0.01), and after recovery in the n-3 group (p=0.00807). Procaspase-9 increased during immobilization (p=0.02) and remained elevated through recovery (p=0.00593), with a notable increase in the n-3 group after recovery(p=0.00923). BAX increased in recovery in the n-3 group (p=0.00137) whereas it increased during immobilisation in the placebo group (p=0.02). BCL2 decreased post-recovery (p=0.00671) and the ratio of BCL2:BAX decreased during immobilization (p<0.001) and remained low through recovery (p<0.0001) in the placebo group, whereas the BCL2:BAX ratio decreased post-recovery in the n-3 group (p=0.00712). There was no effect of immobilization or supplementation on OPA1 or FIS1. Our findings show that mitochondrial %AD did not change during immobilization, but decreased in recovery specifically in the SS and central IMF regions of the myocyte. Furthermore, we found that immobilization increased markers of apoptosis and autophagy, but not mitochondrial fusion or fission, and that supplementation attenuated these changes until after recovery. This highlights the importance of considering recovery periods after immobilization and adds to our understanding of how immobilization and n-3 supplementation influence muscle metabolic health. This study was supported with a Canadian Institutes of Health Research Award to S.M. Phillips and a Natural Sciences and Engineering Research Council of Canada Award to M.C Devries This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
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How this classification was reachedexpand
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 | 0.000 | 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 | 0.000 |
| 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".