Lipotoxic Palmitate Impairs the Rate of β-Oxidation and Citric Acid Cycle Flux in Rat Neonatal Cardiomyocytes
Bibliographic record
Abstract
BACKGROUND/AIMS: Diabetic hearts exhibit intracellular lipid accumulation. This suggests that the degree of fatty acid oxidation (FAO) in these hearts is insufficient to handle the elevated lipid uptake. We previously showed that palmitate impaired the rate of FAO in primary rat neonatal cardiomyocytes. Here we were interested in characterizing the site of FAO impairment induced by palmitate since it may shed light on the metabolic dysfunction that leads to lipid accumulation in diabetic hearts. METHODS: We measured fatty acid oxidation, acetyl-CoA oxidation, and carnitine palmitoyl transferase (Cpt1b) activity. We measured both forward and reverse aconitase activity, as well as NAD+ dependent isocitrate dehydrogenase activity. We also measured reactive oxygen species using the 2', 7'-Dichlorofluorescin Diacetate (DCFDA) assay. Finally we used thin layer chromatography to assess diacylglycerol (DAG) levels. RESULTS: We found that palmitate significantly impaired mitochondrial β-oxidation as well as citric acid cycle flux, but not Cpt1b activity. Palmitate negatively affected net aconitase activity and isocitrate dehydrogenase activity. The impaired enzyme activities were not due to oxidative stress but may be due to DAG mediated PKC activation. CONCLUSION: This work demonstrates that palmitate, a highly abundant fatty acid in human diets, causes impaired β-oxidation and citric acid cycle flux in primary neonatal cardiomyocytes. This metabolic defect occurs prior to cell death suggesting that it is a cause, rather than a consequence of palmitate mediated lipotoxicity. This impaired mitochondrial metabolism can have important implications for metabolic diseases such as diabetes and obesity.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 teacher head, 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".