Folic Acid Supplementation of Female Mice, with or without Vitamin B-12, before and during Pregnancy and Lactation Programs Adiposity and Vascular Health in Adult Male Offspring

Abstract The developmental origins of health and disease theory suggest that disturbances in the fetal and early postnatal environment contribute to chronic adulthood diseases, such as type 2 diabetes and cardiovascular disease. Greater adiposity and insulin resistance have been reported in children of women with high erythrocyte folate but poor vitamin B-12 status during pregnancy. The mechanisms underlying this relation are not known. The objective of this study was to investigate the effects of maternal supplemental folic acid, with or without vitamin B-12, on adiposity, glucose homeostasis, and vascular health in adult male offspring mice. Female C57BL/6J mice were fed a control diet (M-CON, 2 mg folic acid/kg, 50 μg vitamin B-12/kg) or a folic acid-supplemented diet with [10 mg folic acid/kg, 50 μg vitamin B-12/kg (SFA+B12)] or without [10 mg folic acid/kg, no vitamin B-12 (SFA-B12)] vitamin B-12 for 6 wk before mating and during pregnancy and lactation. The offspring were weaned onto a control diet (16% energy from fat) or a western diet (45% energy from fat) until 23 wk of age. The effects of maternal diet on adiposity, vascular function, and glucose tolerance were assessed in 6 groups of adult male offspring: control diet-fed M-CON, SFA+B12, and SFA-B12 and western diet-fed M-CON, SFA+B12, and SFA-B12. Control and western diet-fed SFA-B12 and SFA+B12 offspring had smaller visceral and subcutaneous adipose tissue than M-CON offspring (P