Folic acid content of diets during pregnancy imprint early post‐partum hepatic methyl‐metabolism and insulin resistance in Wistar rat dams
Notice bibliographique
Résumé
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
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».