SUN-077 In Utero Growth Restriction Induces an Early Metabolic Shift in Fetal Rat Heart
Bibliographic record
Abstract
Adverse uterine environment may expose newborns to develop metabolic diseases later in their life. The in-utero growth restriction (IUGR) is an immediate outcome of a sub-optimal womb environment, where the fetus cannot reach its full growth potential. We have developed an animal model of IUGR based on a low-sodium diet given to dams during the last week of gestation. We showed that the isocaloric low-sodium diet reduces maternal blood volume expansion, causing poor placental perfusion, low placental weight and subsequent IUGR in offspring. Redistribution of blood flow in the fetus was observed, causing a preferential perfusion to major organs, such as the heart. Consistent with this, adult offspring showed an increase in blood pressure and remodeling of cardiomyocytes occurs in adult female, suggesting metabolic changes in cardiac function. In this study, we address whether the IUGR induced-stress leads to metabolic changes in fetal cardiomyocytes to adapt their energy-production process and lipid utilization. At 22 days of gestation, hearts were collected from IUGR and control fetuses, and homogenized. Gene expression profile as well as protein levels were analyzed. We observed an increased expression of critical genes involved in lipid metabolism, such as long chain fatty acid receptor CD36, carnitine palmitoyltransferase CPT1a, and also key enzymes of long chain fatty acid beta-oxidation in IUGR heart. In addition, our results indicate an increase in mitochondrial biogenesis. To address whether changes in lipid metabolite profile might prevail, we performed lipidomic MS analysis in heart homogenates. Lipidomics showed significant accumulation of very long and long-chain fatty acids in the context of IUGR and when comparing males and females. These changes could be reminiscent of an adaptation in the use of fatty acids for energy production. Altogether, these findings suggest that fetal IUGR cardiac cells may rely more on the use of lipids as an energy source, compared to same age control cells. Such alterations in energy metabolism in fetal IUGR cardiomyocytes are consistent with an early metabolic shift to favor lipids as the main energy source. This shift normally occurs in the neonatal life to adapt to an extra-uterine environment. Therefore, our findings suggest that adaptation to an altered placental perfusion results in an early cardiac metabolic remodeling that might predispose individuals to metabolic disorders later in their life. Sources of Research Support: Fond de Recherche Québécois en Santé (FRQS) and Canadian Institutes of Health Research (CIHR).
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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 | 0.001 | 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) | 0.000 | 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".