Deletion Of CARM1 In Skeletal Muscle Attenuates Fasting-induced Atrophy
Bibliographic record
Abstract
Coactivator-associated Arginine Methyltransferase 1 (CARM1) belongs to a family of enzymes known as protein arginine methyltransferases (PRMTs) that transfer methyl groups onto target proteins. CARM1 has recently been identified as a critical regulator of autophagic and atrophic processes in muscle via its influence on transcription factor EB (TFEB) and forkhead box protein O3 (FOXO3)-dependent transcription. Although knocking out CARM1 in skeletal muscle significantly blunts the progression of denervation-induced muscle wasting, the impact of CARM1 on the regulation of skeletal muscle plasticity remains to be elucidated. PURPOSE: To further understand the role of CARM1 during atrophy-induced skeletal muscle remodelling. METHODS: To investigate the function of CARM1 in muscle we employed the Cre/loxP system to generate skeletal muscle-specific CARM1 knockout (mKO) mice. In addition, fasting was used to evoke physiologically robust and reproducible muscle atrophy, which provided a stimulus to examine the role of CARM1 during tissue remodelling. Wild type (WT) and mKO mice were deprived of food for a period of 48 hours. Hematoxylin and eosin staining analyses were performed to assess cross-sectional area (CSA) in the extensor digitorum longus muscle. We also employed immunoprecipitation and Western blot analyses to examine protein interactions and protein content, respectively, in fed and fasted tibialis anterior muscles. RESULTS: Our CSA analyses showed that CARM1 deletion in skeletal muscle significantly mitigated fasting-induced atrophy. We detected an interaction between CARM1 and TFEB, as well as between CARM1 and FOXO3 in WT fed and fasted muscles. Moreover, we observed a main effect (p < 0.05) of genotype on muscle atrophy F box (MAFbx) protein content after 48 hours of fasting. Relative to the WT fed group, fasting induced a significant 1.4-fold increase in MAFbx protein levels in WT animals that was abolished in the absence of CARM1. CONCLUSION: These results highlight the importance of CARM1 for driving the muscle atrophy program in response to food deprivation. Targeting the expression and/or activity of CARM1 may offer protection against various forms of muscle atrophy.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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".