Effects of low-dose leucine supplementation on gastrocnemius muscle mitochondrial content and protein turnover in tumor-bearing mice
Bibliographic record
Abstract
Many forms of cancer are associated with loss of lean body mass, commonly attributed to decreased protein synthesis and stimulation of proteolytic pathways within the skeletal muscle. Leucine has been shown to improve protein synthesis, insulin signaling, and mitochondrial biogenesis, which are key signaling pathways influenced by tumor signaling. The purpose of this study was to examine the effects of leucine supplementation on mitochondrial biogenesis and protein turnover in tumor-bearing mice. Twenty male C57BL/6 mice were divided into 4 groups (n = 5): Chow, leucine (Leu), Lewis lung carcinoma (LLC) implant, and LLC+Leu. At 9–10 weeks of age, mice were inoculated and supplemented with 5% leucine (w/w) in the diet. C2C12 myotubes were treated with 2.5 mmol/L leucine and 25% LLC conditioned media to further elucidate the direct influence of the tumor and leucine on the muscle. Measures of protein synthesis, mitochondrial biogenesis, and inflammation in the gastrocnemius were assessed via Western blot analysis. Gastrocnemius mass was decreased in LLC+Leu relative to LLC (p = 0.040). Relative protein synthesis rate was decreased in LLC mice (p = 0.001). No change in protein synthesis was observed in myotubes. Phosphorylation of STAT3 was decreased in the Leu group relative to the control in both mice (p = 0.019) and myotubes (p = 0.02), but did not significantly attenuate the inflammatory effect of LLC implantation (p = 0.619). LLC decreased markers of mitochondrial content; however, PGC-1α was increased in LLC+Leu relative to LLC (p = 0.001). While leucine supplementation was unable to preserve protein synthesis or mitochondrial content associated with LLC implantation, it was able to increase mitochondrial biogenesis signaling. Novelty This study provides novel insights on the effect of leucine supplementation on mitochondrial biogenesis and protein turnover in tumor-bearing mice. Leucine increased signaling for mitochondrial biogenesis in the skeletal muscle. Leucine supplementation decreased inflammatory signaling in skeletal muscle.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".