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UBC Theses and Dissertations

Programming of adult metabolic phenotype by maternal dietary folic acid and vitamin B12 imbalance in mice Aleliunas, Rika


Prenatal and early postnatal nutrient status influences metabolic health in adulthood. A study from India reported that children born to women with high folate and low vitamin B12 status during pregnancy had increased adiposity and insulin resistance. Many countries, including Canada, fortify their grain products with folic acid. In Canada, women have adequate folate status but 1 in 20 may be vitamin B12 deficient. Currently, the metabolic consequences of developmental exposure to high folic acid, with or without vitamin B12 deficiency, are unknown. Female C57BL/6J mice were fed diets high in folic acid, with (HFA+B12) and without (HFA-B12) adequate vitamin B12, or a control diet throughout breeding, pregnancy and lactation. Offspring were weaned onto a control or western-type diet (WTD) for 30 weeks. Maternal and post-weaning diets affected visceral (P<0.01) and subcutaneous fat accumulation (P<0.05) at 20 weeks post-weaning. An interaction between maternal and post-weaning diet was observed in the retroperitoneal fat depot; WTD-fed mice with developmental exposure to HFA-B12 and HFA+B12 diets had decreased retroperitoneal fat accumulation relative to those exposed to maternal control diet. Maternal and post-weaning diets interacted at 30 weeks post-weaning to modify fasting insulin concentrations; in control-fed mice, those with developmental exposure to HFA-B12 had increased fasting insulin concentrations (P<0.05) relative to those with exposure to maternal control and HFA+B12 diets. Maternal and post-weaning diets interacted to affect vascular function of the mesenteric artery at 20 weeks post-weaning. Endothelium-mediated smooth muscle relaxation was decreased in WTD-fed mice with developmental exposure to HFA-B12 diet relative maternal control and HFA+B12 diet-exposed groups (P<0.05). Control-fed mice with developmental exposure to HFA-B12 and HFA+B12 diet had decreased mesenteric artery basal nitric oxide production relative to maternal controls (P<0.05). Developmental exposure to high folic acid (with and without vitamin B12) was associated with decreased NADPH oxidase subunit expression in the aorta (P<0.05). These findings demonstrate that developmental exposure to folic acid and vitamin B12 imbalance interacts with post-weaning diet to program the metabolic response in adult mice. Further studies are warranted to determine the mechanisms behind such effects and to determine the need for vitamin B12 supplementation during pregnancy.

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