Poster Topical Area: Maternal, Perinatal and Pediatric Nutrition

Location: Hall D

Poster Board Number: 353

P13-095 - Gestational Folic Acid and 5-Methyltetrahydrofolate Differentially Affect Hepatic DNMTs in Wistar Rat Female Offspring at Birth and Later Life Phenotype.

Sunday, Jun 10
8:00 AM – 6:00 PM

Folic acid (FA, synthetic folate) intakes above requirements during pregnancy lead to an increased risk of obesity in Wistar rat offspring post-weaning (PW). High FA also associates with high unmetabolized FA in the circulation indicating it is not easily converted in the liver to its bioactive form. Folates are key components of the 1-carbon cycle which produce the substrate required by DNA methyltransferases (DNMTs) for methylation reactions, and thus perturbations in its metabolism may alter methylation of key regulatory genes involved in energy homeostasis. 5-methyltetrahydrofolate (MTHF), the more bioactive form of folate, has recently become available as a dietary supplement. However, the long-term metabolic consequences of different folate forms on offspring health have not been reported.

Objective: This study investigated the effects of gestational folate form and dose on hepatic DNMT activity and expression in female offspring at birth and long-term body weight and food intake.

Methods: Pregnant Wistar rats were fed an AIN-93G diet with recommended FA (1X, control, 2mg/kg), 5X-FA, or equimolar levels of MTHF and then the control diet during lactation. Upon weaning, female offspring were fed a high-fat (45% fat) diet until 19 weeks. Hepatic DNMT activity and mRNA expression of maintenance methyltransferase (Dnmt1) and de novo methyltransferases (Dnmt3a/b) were measured at birth in female pups as an index of methylation potential and PW body weight and food intake were measured.

Results: A lasting and differential effect of gestational folate dose and form on female offspring phenotype was observed. PW body weight was lower in 5X-FA female offspring compared to all other diet groups (~12%, p<0.001) but food intake was only lower compared to 1X-MTHF offspring (p<0.05). Offspring from 1X-MTHF dams also had higher hepatic Dnmt3a (p<0.05) mRNA expression at birth compared to other diet groups, but Dnmt1/3­b expression and total DNMT enzyme activity were not affected by gestational diet.

Conclusion: Gestational folate dose and form differentially affect long-term body weight and food intake of the female offspring, but this is not fully explained through DNMT activity and expression at birth. Other epigenetic mechanisms are currently being investigated to help explain these findings.





Funding Source: Canadian Institute of Health Research, Institute of Nutrition, Metabolism and Diabetes (CIHR-INMD), Reference MOP-130286.

CoAuthors: Terry Sa – University of Toronto; Rola Hammoud, MSc – University of Toronto; Neil Yang, MSc – University of Toronto; Mandy Ho, HBSc – University of Toronto; Diptendu Chatterjee, PhD – University of Toronto; Ruslan Kubant, PhD – University of Toronto; G. Harvey Anderson , PhD – University of Toronto

Emanuela Pannia

PhD
University of Toronto
Toronto, Ontario, Canada