Evidence of mitochondrial nitrosative damage and energy stress behind omega‐6 PUFA induced cardiac dysfunction
Bibliographic record
Abstract
Heightened awareness of obesity and its complications has led to an indiscriminate substitution of atherogenic saturated cooking fats with “heart‐friendly” refined vegetable oils like sunflower oil, rich in ω‐6 polyunsaturated fatty acids (PUFA) in the Western diet. Interestingly, recent studies have suggested ω‐6 PUFA to be pro‐inflammatory for the coronary vasculature. However, its effects on the heart muscle itself remain obscure. Thus, we examined the in vivo signaling in Wistar rat hearts following a low ω‐6 PUFA (10% of energy, LP) or high ω‐6 PUFA (40% of energy, HP) diet for 4 weeks. HP feeding increased phospholipase A 2 and breakdown of phospholipids like mitochondrial cardiolipin crucial for ATP production. HP hearts also demonstrated increased inducible nitric oxide synthase expression and loss of Mn superoxide dismutase, a mitochondrial antioxidant. This was followed by an increase in nitrotyrosine, a biomarker for peroxynitrite radical. As peroxynitrite oxidatively damages mitochondrial DNA (mDNA), immunohistochemistry of 8‐oxo‐7,8‐dihydroguanosine, an oxidized DNA byproduct, revealed extensive mDNA damage in HP hearts. This was accompanied with decreased gene expression of ND1 and ATPase 6, respiratory subunits encoded by the mDNA. Such a loss of respiratory subunits along with cardiolipin loss could precipitate cardiac energy deficit. As a functional confirmation, HP hearts failed specifically at elevated afterloads (135mm Hg) indicating a lack of energy reserve that was supported by an increase in phosphorylated AMP kinase. Hence, contrary to popular belief as being beneficial, chronic excess of ω‐6 PUFA with its predisposition to induce mitochondrial nitrosative damage and energy deficit, could initiate myocardial dysfunction. Funded by the Heart and Stroke Foundation of BC and Yukon, Canada
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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) | 0.002 | 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".