Mechanically Overloaded Plantaris Muscles Display Ectopic Sarcolipin Expression that is Required for Myofiber Hypertrophy and Remodelling
Bibliographic record
Abstract
Sarcolipin (SLN) is a regulator of the sarco(endo)plasmic reticulum Ca 2+ ‐ATPase (SERCA) pump and is critical in mediating muscle based thermogenesis and combating diet‐induced obesity. Unpublished work from our laboratory has shown that SLN may be important in maintaining muscle mass. Specifically, in phospholamban overexpressing mice ( Pln OE ), a mouse model that accurately recapitulates human centronuclear myopathy and exhibits severe muscle atrophy, we found that genetic deletion of Sln exaggerated the loss in soleus muscle size. As this reduction in muscle size was associated with a failure to promote type II fiber hypertrophy and fast‐to‐slow fiber type shifts, we questioned whether Sln deletion would also lead to similar defects in mechanically overloaded plantaris muscles that normally undergo comparable adaptations. To this end, we mechanically overloaded plantaris muscles from wild‐type (WT) and Sln ‐null ( Sln KO ) mice for 2 weeks by performing soleus and gastrocnemius tenotomy. Strikingly, after 2 weeks of adaptation, the plantaris muscles from WT muscles displayed ectopic expression of SLN. This is particularly impressive since SLN's expression is typically restricted to slow‐oxidative muscles from the adult mouse. Furthermore, after two weeks of mechanical overload, the WT plantaris myofibers displayed significant hypertrophy (+22% to +48%, P < 0.0001) and fast‐to‐slow fiber type transitions with a significant increase in type I( P = 0.03) and type IIA ( P = 0.05) fiber proportions, respectively; however, these adaptations to mechanical overload were not observed in Sln KO mice. Since calcineurin signaling is largely responsible for the cellular adaptations that occur with the mechanical overload stimulus, we examined the phosphorylation status of its well‐known substrate, nuclear factor of activated T‐cells (pNFAT). Strikingly, WT overloaded plantaris muscles showed significantly lower pNFAT compared with WT sham (−61%, P = 0.01), whereas pNFAT in overloaded Sln KO plantaris muscles was not significantly different from Sln KO sham ( P = 0.11). Taken together, these results show for the first time, that SLN is recruited in mechanically overloaded plantaris muscles, and is critical in stimulating calcineurin‐mediated muscle growth and remodeling. Support or Funding Information This work was supported by the Canadian Institutes of Health Research (CIHR; MOP 86618 and MOP 47296 to A.R.T).
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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) | 0.001 | 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) | 0.003 | 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".