Folic acid content of diets during pregnancy imprint early post‐partum hepatic methyl‐metabolism and insulin resistance in Wistar rat dams
Bibliographic record
Abstract
Intake recommendations for folic acid (FA, synthetic form of folate) are often exceeded by 2.5–7‐fold in North America, raising concern for its potential adverse effects on maternal and child health. In Wistar rats, high (10×) but non‐toxic FA intakes during pregnancy lead to obesity, insulin resistance and dysregulation of central and peripheral energy metabolism‐related genes in both offspring and dams later‐in‐life. Moreover, high FA fed to rat offspring post‐weaning was reported to induce inhibitory effects on hepatic methyl‐metabolism, limiting the conversion of FA to its biologically active form methyltetrahydrofolate (MTHF). This study examined the effects of dose of FA in maternal diets on early post‐partum phenotype (body weight and food intake), folate status, methyl metabolism in liver, and insulin resistance in the dams. During pregnancy, Wistar rats (n=12/group) were fed an AIN‐93G diet containing five levels of FA: 0× (deficient), 1× (recommended, 2mg FA/kg), 2.5× (moderate), 5× (high) and 10× (very high). Dams were fed the recommended diet during lactation and their first week post‐weaning and then terminated. At 1‐week post‐weaning, mRNA expression of methyl metabolism‐related genes in liver, including folate receptor ( FolR ), Mthf reductase ( Mthfr ), betaine‐homocysteine S‐methyltransferase ( Bhmt ) and methionine synthase ( Mtr ) were assessed by real‐time qPCR. Unmetabolized FA and folate metabolites were analyzed in blood and liver by high performance liquid chromatography (HPLC). Fasting plasma glucose and insulin levels were measured, and insulin resistance was evaluated via surrogate index: the homeostatic model assessment insulin resistance (HOMA‐IR). The results show a lasting effect of the diets consumed during pregnancy on the dams four weeks after giving birth. Dams fed 0X, 5× and 10X‐FA during pregnancy had lower hepatic mRNA expression of Mthfr (2.2‐fold, p<0.0001) and Mtr (3.5‐fold, p<0.001) compared to control and showed no change in folate status in liver. However, deficient and very high FA maternal diets led to higher MTHF in blood compared to control suggestive of dysregulation of one‐carbon pathways. Dams fed 5X‐FA also showed higher plasma insulin (p<0.01) and HOMA‐IR (p<0.05) then dams fed the control diet, indicative of the development of insulin resistance. Body weight, food intake and unmetabolized FA levels were not affected by maternal diets at 1‐week post‐weaning. In conclusion, deficient or excess FA in diets consumed during pregnancy imprinted methyl‐metabolism and insulin regulation in the dam to 1‐week post‐weaning, which may contribute to their long‐term adverse effects as previously found in the dams. Support or Funding Information Canadian Institute of Health Research, Institute of Nutrition, Metabolism and Diabetes (CIHR‐INMD), Reference MOP‐130286
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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".