FOXO1‐induced Atrophy Changes in Phospholipid Profiles of Skeletal Muscle
Bibliographic record
Abstract
Exercise training influences phospholipid fatty acid composition in skeletal muscle and these changes are associated with physiological phenotypes. Recently we have found that peroxisome proliferator‐activated receptor γ coactivator 1α (PGC‐1α), a nuclear receptor coactivator, affected lipid profiles in skeletal muscle and increased several phospholipid species in glycolytic muscle, namely phosphatidylcholine (PC) (18:0/22:6) and phosphatidylethanolamine (PE) (18:0/22:6). We also found that exercise training increased PC (18:0/22:6) and PE (18:0/22:6) in glycolytic muscle and that PGC‐1α was required for these alterations. On the other hand, a decrease in docosahexaenoic acid [22:6 (n‐3)] from the skeletal muscle phospholipid fraction was observed in dystrophic mdx mice, suggesting changes of phospholipid fatty acid composition related with physiological phenotypes of skeletal muscle. However, the molecular mechanism of this influence on compositional changes is poorly understood. Forkhead box protein O1 (FOXO1) is a transcriptional factor that plays an important role in regulation of skeletal muscle mass. Because we have demonstrated that muscle‐specific overexpression of FOXO1 is sufficient to cause skeletal muscle atrophy in vivo, we speculated that FOXO1 contribute to the atrophy‐mediated change in phospholipid fatty acid composition. To determine the role of FOXO1, we performed lipidomics analyses of skeletal muscle from genetically modified mice that overexpress FOXO1 in skeletal muscle. After lipid extraction from EDL or soleus by Bligh and Dyer method, the lipid samples were injected into LC‐MS and determined peaks were re‐analyzed by MS/MS for identification of lipid species. Using these data, principal component analysis was done to classified the changes of lipid species depending on muscle fiber type and FOXO1 expression. As a result, we observed that PC and PE containing specific fatty acid species changed in both of EDL and soleus derived from mice that overexpress FOXO1 in skeletal muscle. From these results, it was suggested that FOXO1 expression changed fatty acid composition of PC and PE and these changes might be involved in the physiological phenotype of muscle atrophy. Support or Funding Information This study was supported by the Council for Science, Technology and Innovation (CSTI), Cross‐ministerial Strategic Innovation Promotion Program (SIP, No.14533567), and “Technologies for creating next‐generation agriculture, forestry and fisheries” (funding agency: Bio‐oriented Technology Research Advancement Institution, NARO), The Tojuro Iijima Foundation for Food Science and Technology (Chiba, Japan), Grants‐in‐Aid for Scientific Research (KAKENHI, No. 26282184, 26560400, 21300240) from the Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT, Tokyo), The Uehara Memorial Foundation (Tokyo, Japan), The Kao Research Council for the Study of Healthcare Science (Tokyo, Japan, No. A‐31006), and University of Shizuoka Grant for Scientific and Educational Research.
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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 | 0.000 |
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".