Ketones can become the major fuel source for the heart but do not increase cardiac efficiency
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Bibliographic record
Abstract
AIMS: Ketones have been proposed to be a 'thrifty' fuel for the heart and increasing cardiac ketone oxidation can be cardioprotective. However, it is unclear how much ketone oxidation can contribute to energy production in the heart, nor whether increasing ketone oxidation increases cardiac efficiency. Therefore, our goal was to determine to what extent high levels of the ketone body, β-hydroxybutyrate (βOHB), contributes to cardiac energy production, and whether this influences cardiac efficiency. METHODS AND RESULTS: Isolated working mice hearts were aerobically perfused with palmitate (0.8 mM or 1.2 mM), glucose (5 mM) and increasing concentrations of βOHB (0, 0.6, 2.0 mM). Subsequently, oxidation of these substrates, cardiac function, and cardiac efficiency were assessed. Increasing βOHB concentrations increased myocardial ketone oxidation rates without affecting glucose or fatty acid oxidation rates where normal physiological levels of glucose (5 mM) and fatty acid (0.8 mM) are present. Notably, ketones became the major fuel source for the heart at 2.0 mM βOHB (at both low or high fatty acid concentrations), with the elevated ketone oxidation rates markedly increasing tricarboxylic acid (TCA) cycle activity, producing a large amount of reducing equivalents and finally, increasing myocardial oxygen consumption. However, the marked increase in ketone oxidation at high concentrations of βOHB was not accompanied by an increase in cardiac work, suggesting that a mismatch between excess reduced equivalents production from ketone oxidation and cardiac adenosine triphosphate production. Consequently, cardiac efficiency decreased when the heart was exposed to higher ketone levels. CONCLUSIONS: We demonstrate that while ketones can become the major fuel source for the heart, they do not increase cardiac efficiency, which also underscores the importance of recognizing ketones as a major fuel source for the heart in times of starvation, consumption of a ketogenic diet or poorly controlled diabetes.
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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 | 0.008 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.005 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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 it