Metabolic effects of a high‐fat diet post‐weaning after low maternal dietary folate during pregnancy and lactation

SCOPE: Investigate the influence of low‐folate supply during pregnancy and lactation on obesity and markers of the metabolic syndrome in offspring, and how provision of a high‐fat diet post weaning may exacerbate the resultant phenotype. METHODS AND RESULTS: Female C57Bl/6 mice were randomized to low or normal folate diets (0.4 or 2 mg folic acid/kg diet) prior to and during pregnancy and lactation. At 4 wk of age, offspring were randomized to high‐ or low‐fat diets, weighed weekly and food intake assessed at 9 and 18 wk old. Adiposity was measured at 3 and 6 months. Plasma glucose and triacylglycerol (TAG) concentrations were measured at 6 months. Maternal folate supply did not influence adult offspring body weight or adiposity. High‐fat feeding post weaning increased body weight and adiposity at 3 and 6 months (p > 0.001). Maternal low folate lowered plasma glucose (p = 0.010) but increased plasma TAG (p = 0.048). High‐fat feeding post weaning increased plasma glucose and TAG (p = 0.023, p = 0.049 respectively). Offspring from folate‐depleted (but not folate‐adequate) dams had 30% higher TAG concentration when fed the high‐fat diet from weaning (p = 0.005 for interaction). CONCLUSION: Inadequate maternal folate intake has long‐term effects on offspring metabolism, manifested as increased circulating TAG, particularly in offspring with high‐fat intake post weaning.