Fetal glucose availability: a key regulator of the metabolic, hormonal and contractility profiles of the fetal sheep heart
Bibliographic record
Abstract
Abstract There is an association between fetal growth restriction (FGR) and a poor lifetime cardiac health trajectory. Defining the underlying mechanisms will aid in developing interventions to decrease the contribution of FGR‐born offspring to the global burden of cardiovascular disease. One cause of FGR is maternal undernutrition. In late‐gestation undernutrition (LGUN) fetal glucose supply, a main energy source for the fetal heart, is reduced. This may be a key contributor to altered fetal cardiac development; thus restoration of fetal glucose availability in the LGUN setting may be a viable target for intervention. To investigate the role of glucose availability in fetal heart development, we utilized an established pregnant sheep model of LGUN (50% global nutrient restriction) with or without a continuous intrafetal glucose infusion. LGUN reduced fetal plasma glucose concentrations, resulting in brain sparing that was normalized by intrafetal glucose infusion. LGUN decreased the protein abundance of oxidative phosphorylation complexes 1 and 3; however glucose infusion returned complex 3 abundance to that of controls. LGUN increased the phosphorylation of contractility and hypertrophy marker CAMKII, which was associated with increased left ventricular cardiac output; however intrafetal glucose infusion normalized CAMKII. Our findings demonstrate that glucose plays a specific role in regulating cardiac development in utero , highlighting the importance of adequate maternal nutrition in late gestation. image Key points Maternal late‐gestation undernutrition (LGUN) reduces fetal plasma glucose concentrations. To investigate the role of glucose availability in fetal left ventricle (LV) development, we assessed whether LGUN‐induced alterations in the contractility, metabolic and hormonal profiles can be ameliorated in LGUN fetuses receiving glucose infusion (LGUN+G). Relative brain weight was increased in LGUN compared to controls and restored in LGUN+G despite fetal glucose infusion only partially normalizing fetal plasma glucose concentrations to that of controls. LGUN decreased cardiac oxidative phosphorylation (OXPHOS)complex 1 and 3 abundance, and LGUN+G restored complex 3 to that of controls. LGUN increased the activation of the contractility marker, Ca 2+ /calmodulin‐dependent protein kinase II (p‐CAMKII), but restored in LGUN+G. The magnetic resonance imaging measure of the LV cardiac output was positively correlated with p‐CAMKII expression in LGUN. This study highlights the role of in utero glucose availability in regulating the abundance of fetal LV OXPHOS complex 3 and CAMKII activation in utero .
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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) | 0.001 | 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".