Impact of a human missense UCP3 polymorphism on the plasma metabolomic profile: support for a mitochondrial fuel‐partitioning role for UCP3 (248.4)
Bibliographic record
Abstract
Skeletal muscle uncoupling protein 3 (UCP3) is thought to facilitate fatty acid oxidation (FAO) and protect against excess mitochondrial (MITO) reactive oxygen species (ROS); however, this has yet to be conclusively proven in human studies. We hypothesized that a comprehensive plasma metabolomic characterization of a human UCP3 polymorphism would identify metabolites associated with decreased skeletal muscle FAO and oxidative stress. We measured 490 metabolites using three independent metabolomics platforms in obese African‐American women with or without type 2 diabetes (T2D) containing a missense G304A (G/A) UCP3 polymorphism. Partial least squares‐discriminant analysis (PLS‐DA) revealed altered amino acid profiles and metabolites consistent with enhanced glycolytic oxidation in the context of reduced UCP3 function. UCP3 G/A genotype also revealed decreases in plasma amino acids involved in glutathione metabolism and markers of glutathione synthesis. Stearoylethanolamide (SEA), a putative modulator of MITO oxidative phosphorylation and biogenesis was also significantly elevated in T2D UCP3 G/A individuals. Our results support the idea that UCP3 is involved in regulating muscle MITO fuel selection by promoting fatty acid combustion, perhaps via mechanisms involving ROS signaling. Grant Funding Source : Supported by: NIH‐NIDDK R01DK078328‐01, UAB‐CCTS UL1 RR025777, WCMC NIH 1 U24 DK097154, USDA‐ARS
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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 | 0.001 | 0.000 |
| 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".