Sex-dependent benefit of B vitamins on cardiac function and lipid metabolism in a murine model of heart failure with reduced ejection fraction
Bibliographic record
Abstract
Background: Heart failure (HF) is a global health problem requiring more effective therapeutic alternatives. While HF involves disturbances in cardiac metabolism associated with lipidomic remodeling, there is a lack of approaches to specifically target cardiac metabolism. Recently, it has been shown in murine models of HF, that the use of nicotinamide riboside (vitamin B3) alone or the combination of B9 and B12 vitamins, before the development of HF, improved cardiac metabolism and function. Our hypothesis is that the combination of B3, B9 and B12 vitamins, used when HF is declared, will improve lipid metabolism, cardiac function and survival. The aim of this study is to evaluate the curative benefit of a synthetic diet enriched with the combination of these three vitamins (VitB) in a murine model of HF with reduced ejection fraction (EF). Method: Pressure overload was induced by constriction of the transverse aorta (TAC) in male and female mice. After 4 weeks, TAC mice reaching a pressure gradient of 60 mmHg, an increased left ventricle mass >30% and a reduced EF >10%, were randomized to a VitB-enriched diet or not. Results: In females, VitB improved survival and cardiac hypertrophy (-24%, p<0.05) as well as EF (+22%, p<0.01). We also observed a reduction of cardiac fibrosis emphasized by a significant decrease expression of collagen 1a and 3 (-30% and -19% respectively) and hydroxyproline concentration (-32%, p<0.01). No benefit was observed in males in terms of survival, cardiac function and fibrosis. Untargeted mass spectrometry (MS)-based lipidomics on plasmas at 8 weeks of treatment showed a decrease in several individual triglycerides (TG from 43 to 48 %; p<0.05) in TAC females that were normalized by VitB. In contrast, in TAC males, most of the annotated TGs were increased (from ̴35 to 210%; p<0.05), a profile exacerbated upon VitB treatment. MSMS identification of TG side chains revealed a differential profile in terms of fatty acid composition according to sex and treatment. In VitB females, longer and polyunsaturated TGs (53 to 60C; 5 to 12 double bonds) were significantly increased (1.6- to 2.1-fold) while, in VitB males, the increased TGs (1.2- to 5.2-fold) were shorter (24C to 48C) and saturated (no double bonds). Conclusion: Our study pointed out a sexual dimorphism in the response to VitB treatment in HF in favor of females and implying a lipidomic remodeling promoting cardioprotective polyunsaturated TGs. European Research Area Network on Cardiovascular Diseases, Canadian Institutes of Health Research, Fonds de recherche du Québec - Santé. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
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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".