High 5-Methyletetrahydrofolate and Folic Acid Gestational Diets Differ on Leptin-Dependent Hypothalamic Genes Regulating Food Intake in Female Offspring
Bibliographic record
Abstract
While the replacement of folic acid (FA) with the bioactive folate form 5-methyltetrahydrofolate (MTHF) is gaining popularity, a comparison of their effects during pregnancy is limited. In a comparison of maternal intakes of FA and MTHF at recommended or high (5X) doses in Wistar rat dams, we found that dams fed 5X MTHF gained > 70% more weight and ate 8% more food to 19-weeks post weaning (PW) than those fed the high FA diet (Nutrients. 2021;13:48). However, both high dose diets resulted in dysregulation of leptin and central energy regulatory systems. The objective of this study was to compare the effect of gestational FA and MTHF diets on metabolic response and leptin-dependent hypothalamic energy-regulatory genes in the brain of their female offspring. Pregnant Wistar rats were fed an AIN-93G diet with 1X recommended (2mg/kg diet) or 5X FA or equimolar MTHF. At weaning, female offspring were fed a high-fat diet until 19-weeks PW. Body weight, food intake, adiposity, plasma leptin, and gene expression of leptin signaling and related candidate genes in the hypothalamus were measured. Similar to the mothers, the 5X-MTHF gestational diet resulted in offspring with higher weight (>15%, P < 0.01) independent of visceral adiposity, and higher food intake (8% P < 0.01) compared to those born to dams fed the 5X-FA, but not from the 1X folate diets. Both 5X diets led to higher plasma leptin at birth (60%, P < 0.05) and at 19-weeks PW (40%, P < 0.01) and up-regulated hypothalamic mRNA of the downstream leptin signalling gene, signal transducer and activator of transcription-3 (Stat3). However, only 5X-MTHF offspring had lower expression of leptin receptor (Ob-rB) and higher expression of suppressor of cytokine signaling-3 (Socs-3), an inhibitor of leptin signalling and indicator of central leptin resistance. In contrast, 5X-FA offspring had higher expression (>1.5-fold, P < 0.01) of dopamine and GABA- receptors which are targets of leptin and associated with feeding inhibition and hyperactivity. Folate form and dose during pregnancy affects long-term programming of leptin dependent hypothalamic regulatory pathways in female offspring. Unfavorable differences in response to FA and MTHF were seen at the higher doses, thus neither should be consumed at high intakes. CIHR-INMD; EP by NSERC-CGS.
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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".