Shift in metabolic fuel in acylation-stimulating protein-deficient mice following a high-fat diet
Bibliographic record
Abstract
ASP-deficient mice (C3 KO) have delayed postprandial TG clearance, are hyperphagic, and display increased energy expenditure. Markers of carbohydrate and fatty acid metabolism in the skeletal muscle and heart were examined to evaluate the mechanism. On a high-fat diet, compared with wild-type mice, C3 KO mice have increased energy expenditure, decreased RQ, lower ex vivo glucose oxidation (-39%, P = 0.018), and higher ex vivo fatty acid oxidation (+68%, P = 0.019). They have lower muscle glycogen content (-25%, P < 0.05) and lower activities for the glycolytic enzymes glycogen phosphorylase (-31%, P = 0.005), hexokinase (-43%, P = 0.007), phosphofructokinase (-51%, P < 0.0001), and GAPDH (-15%, P = 0.04). Analysis of mitochondrial enzyme activities revealed that hydroxyacyl-coenzyme A dehydrogenase was higher (+25%, P = 0.004) in C3 KO mice. Furthermore, Western blot analysis of muscle revealed significantly higher fatty acid transporter CD36 (+40%, P = 0.006) and cytochrome c (a marker of mitochondrial content; +69%, P = 0.034) levels in C3 KO mice, whereas the activity of AMP kinase was lower (-48%, P = 0.003). Overall, these results demonstrate a shift in the metabolic potential of skeletal muscle toward increased fatty acid utilization. Whether this is 1) a consequence of decreased adipose tissue storage with repartitioning toward muscle or 2) a direct result of the absence of ASP interaction with the receptor C5L2 in muscle remains to be determined. However, these in vivo data suggest that ASP inhibition could be a potentially viable approach in correcting muscle metabolic dysfunction in obesity.
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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 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| 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".