Role of uncoupling protein‐3 in fatty acid oxidation in skeletal muscle mitochondria
Bibliographic record
Abstract
BACKGROUND : Himms‐Hagen and Harper (Exp Biol Med 2001) hypothesized that uncoupling protein‐3 (UCP3) provides an overflow pathway for fatty acids (FA) in conditions of excess mitochondrial FA supply. Thus when FA flux to mitochondria is greatly elevated, long chain FA‐CoA accumulates in the matrix, sequestering the limited matrix CoA pool and preventing oxidation of partially metabolized FA. UCP3 would act with a mitochondrial thioesterase to liberate CoA and export FA anions. A functional implication of matrix FA anion export by UCP3 is increased FA oxidation (FAO) in conditions of high FA flux. AIM : Directly test the hypothesis that UCP3 facilitates FAO by exporting FA. APPROACH : FAO rates (14CO2 production) were measured in skeletal muscle mitochondria of wild‐type (WT) and UCP3−/− (KO) mice under several conditions: a range of 14C‐palmitate (PA) or 14C‐palmitoylcarnitine (PC) concentrations to simulate low and high FA supply; presence/absence of CoA during PC oxidation to interfere with reactivation of potential exported FA; addition/omission of carnitine during PC oxidation to modify matrix acyl‐CoA/CoA. Generated and exported PA: measured by thin‐layer chromatography. Data analysis: unpaired t‐test or 2‐way ANOVA (n = 4–6). RESULTS: Generated and exported PA were detected, with no difference between WT and KO mitochondria. PA and PC rates were similar between WT and KO, at low and high FA flux, and in the presence/absence of carnitine. Addition of 0.05 μM CoA similarly increased CO2 production in both genotypes. CONCLUSION: Our observations do not support an obligatory role for UCP3 in facilitating FAO or in export of PA in isolated skeletal muscle mitochondria, even when FA supply is greatly elevated. Funding: CIHR
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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".