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.