CKD Remodels Skeletal Muscle Metabolism Toward Carbohydrate Oxidation
Bibliographic record
Abstract
Background: Skeletal muscle health progressively declines from chronic kidney disease (CKD). To test the hypothesis that exercise mitigates abnormal muscle metabolism in CKD, we utilized high-resolution mitochondrial respiration and metabolomics techniques for indices of skeletal muscle carbohydrate and fat metabolism in a progressive CKD rat model. Methods: Animals- 1) Cy/+ (CKD) rats, 2) CKD + wheel running, and 3) normal littermates (NL) (N=12/gr). Running wheel was accessible 24 hr/day 25-35 weeks of age; moderate to severe CKD, respectively. Extensor digitorum longus (EDL) and soleus were harvested at sacrifice. Mitochondrial respiratory subunit complexes were quantified by Western blot. Mitochondrial respiration: Measured in the presence of multiple substrates (Oxygraph-2k, Oroboros). Metabolomics: Targeted mass spectrometry (MS) and nuclear magnetic resonance (NMR) were performed. Results: In the EDL, protein content of Complex 1 was reduced, but pyruvatestimulated respiration increased with CKD wheel running. Metabolomic analysis (MS) of the EDL supported this, as wheel running lowered long-chain fatty acids (C14-18; p<0.05). In the soleus, Complex 1 content decreased and pyruvate-stimulated respiration increased in both CKD and CKD running compared to NL (p<0.05). Soleus MS demonstrated lower long-chain fatty acids (C14-18; p<0.05). Serum NMR demonstrated increased pyruvate and reduced lactate concentrations suggesting greater re-direction of pyruvate to mitochondrial oxidative phosphorylation. Carnitine levels were low in serum and muscle, suggesting impaired transport of fatty acids to the mitochondria. Conclusions: These intriguing results indicate CKD impairs skeletal muscle mitochondrial oxidative capacity despite increased pyruvate oxidation. In addition, metabolomics data suggests impaired fatty acid oxidation that worsened with wheel running due to low carnitine levels. These results suggest dual alterations in response to mild exercise in CKD: 1- impaired fatty acid oxidation from deficient carnitine; 2- enhanced pyruvate oxidation consistent with lower lactate production. These cellular metabolic reprogramming events suggests that skeletal muscle may shift away from fatty acid metabolism towards carbohydrates which may explain why patients with CKD do not experience the usual benefit of exercise. Funding: NIDDK Support
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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) | 0.001 | 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".