The role of protein-mediated transport in regulating mitochondrial long-chain fatty acid oxidation
Bibliographic record
Abstract
This thesis is an investigation of the role of fatty acid translocase (FAT/CD36), plasma membrane associated fatty acid binding protein (FABPpm), and carnitine palmitoyltransferase I (CPTI) in transporting long-chain fatty acids (LCFAs) across mitochondrial membranes. Maximal CPTI activity, as well as the sensitivity of CPTI for its substrate palmitoyl-CoA (P-CoA) and its inhibitor malonyl-CoA (M-CoA), were measured in mitochondria isolated from human vastus lateralis muscles at rest and following muscle contraction. Exercise did not alter maximal CPTI activity or the sensitivity of CPTI for P-CoA. In contrast, exercise progressively attenuated the ability of M-CoA to inhibit CPTI activity. Mitochondrial FAT/CD36 protein content was also measured at rest, during, and following 2 h of cycling at ~60% maximal oxygen uptake. Exercise progressively increased the content of mitochondrial FAT/CD36 (+59%), which was significantly (p < 0.05) correlated with palmitate oxidation during exercise (r = 0.52), while palmitate oxidation was inhibited ~80% by the administration of a specific FAT/CD36 inhibitor. These data suggest that alterations in CPTI M-CoA sensitivity and increases in mitochondrial FAT/CD36 coordinate exercise-induced increases in fatty acid oxidation. FABPpm, another plasma membrane transport protein, has identical amino acid sequence to mitochondrial aspartate aminotransferase (mAspAT). Since FABPpm contributes to plasma membrane fatty acid transport, the role of FABPpm with respect to mitochondrial LCFA transport was investigated. However, unlike FAT/CD36, muscle contraction did not induce an increase in mitochondrial FABPpm protein in rat or human skeletal muscle. In addition, electrotransfecting FABPpm cDNA into rat skeletal muscle upregulated this protein in mitochondria by 80% without altering mitochondrial palmitate oxidation. In contrast, electrotransfection increased mAspAT activity by 90%, and this was correlated (r = 0.75; p < 0.01) with FABPpm protein. These data suggest that FABPpm does not contribute to the regulation of mitochondrial LCFA transport. Previously, it has been suggested that mitochondria from obese individuals contain an inherent dysfunction to oxidize LCFAs. In age-matched lean (BMI = 23.3 ± 0.7 kg·m–2) and obese (BMI = 37.6 ± 2.2 kg·m–2) individuals, isolated mitochondrial palmitate oxidation was not altered. In addition, mitochondrial FAT/CD36 content was not different in lean and obese individuals. In contrast, citrate synthase and β-hydroxyacyl-CoA dehydrogenase, common markers of total mitochondrial content, were decreased with obesity. Therefore, the decrease in mitochondrial content appeared to account for the observed reductions in whole-muscle 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 | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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".