Maternal Folic Acid/Vitamin B12 Imbalance Programs Hepatic Gene Expression In Female Offspring

Epidemiological studies reported an association between gestational exposure to high maternal folate and low vitamin B12 (B12) status and greater adiposity and insulin resistance in children. The objective of this study is to examine the effect of developmental exposure to maternal folic acid (FA)/B12 imbalance on programming of adiposity, liver gene expression, and methyl metabolites in adult female offspring. Female C57BL/6 mice were fed a high FA/adequate B12 (HFA+B12), high FA/no B12 (HFA-B12), or control diet 6 weeks prior to mating and through pregnancy and lactation. Female offspring mice were weaned onto the control diet or a Western diet, and fed for 35 weeks (n=6 mice/group). Independent of post weaning diet, female offspring from dams fed the HFA-B12 diet had lower Mtr mRNA. Further, offspring from dams fed the HFA-B12 diet had higher Mthfr and lower Ppara mRNA when they were fed the Western diet, compared to offspring from dams fed the HFA+B12 diet. Western diet-fed offspring from dams fed the HFA-B12 diet also had lower hepatic S-adenosylmethionine concentrations, compared to those from control-fed dams. Unlike the Western diet-fed, control-fed offspring from dams fed the HFA diet (independent of maternal B12) had greater abdominal fat mass. Offspring serum B12 concentrations were positively associated with abdominal fat mass. These findings suggest that developmental exposure to maternal high FA/low B12 programs expression of genes in the liver of adult offspring mice, and that serum B12 concentrations are related to visceral adiposity. Supported by NSERC