Mitochondrial LCFA Oxidation, FAT/CD36 Content and CPTI Activity in Human Skeletal Muscle During Aerobic Exercise
Bibliographic record
Abstract
PURPOSE: Mitochondrial fatty acid transport is a rate-limiting step in long chain fatty acid (LCFA) oxidation, and traditionally was believed to be solely regulated by carnitine palmitoyltransferase I (CPTI). Recently, it has been proposed that mitochondrial LCFA transport may involve fatty acid translocase (FAT)/CD36 in addition to CPTI, however mitochondrial FAT/CD36 has not been studied in human skeletal muscle during exercise. The present study investigated the ability of malonyl-CoA (M-CoA) to inhibit CPTI, and the presence and functional significance of FAT/ CD36 on mitochondria. We hypothesized that exercise induced increases in fatty acid oxidation would occur as a result of decreases in the sensitivity of CPTI to M-CoA and increased mitochondrial FAT/CD36 protein. METHODS: Participants cycled at ∼60% VO2peak for 120 min, and blood and ventilatory data was collected at rest and every 30 minutes during exercise. Purcutaneous needle biopsies were taken from the vastus lateralis at rest, 30 min and following 120 min. Mitochondria were immediately isolated, and used for CPTI activity measurements, palmitate oxidation rates and Western blots for FAT/CD36 protein content (n=15). RESULTS: Whole body fat oxidation rates progressively increased during exercise (p<0.05), and concomitantly M-CoA inhibition of CPTI was progressively attenuated. Compared to rest, 120 min of cycling reduced (p<0.05) the inhibition of 0.7, 2, 5 and 10 uMM-CoAby 16%, 21%, 30% and 34%, respectively. However, exercise did not alter the maximal CPTI activity. Palmitate oxidation rates in isolated mitochondria progressively increased (p<0.05) during exercise, and was positively correlated with whole body fat oxidation rates (r=0.78). Associated with the exercise induced increase in mitochondrial palmitate oxidation was a 63% increase (p<0.05) in mitochondrial FAT/CD36 protein content. Importantly, the addition of sulfo-N-succimidyl oleate, a specific inhibitor of FAT/CD36, reduced mitochondrial palmitate oxidation by ∼80%. CONCLUSIONS: The data suggests that exercise induced increases in fatty acid oxidation occur as a result of decreases in the sensitivity of CPTI to the inhibitor M-CoA and increased mitochondrial FAT/CD36 protein. It is proposed that translocation from an intracellular depot is a feasible explanation. We conclude that these two novel mechanisms are not mutually exclusive, but rather interact to influence LCFA oxidation.
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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 | 0.000 |
| 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".