Abstract
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. 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). 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.
Highlights
The developmental origins of health and disease (DOHaD) hypothesis proposes that exposures during early life mod-Abbreviations: DOHaD, Developmental origins of health and disease; MS, metabolic syndrome; SI, small intestine; TAG, triacylglycerol ulate the risk of developing noncommunicable diseases in adulthood
There was no significant difference between groups for total number of pregnancies/dam (Pearson Chi-square p value = 0.435) and the mean number of days spent on maternal diet for dams with successful pregnancies did not differ between low and normal folate groups (p = 0.415)
There were no significant differences in body weight of offspring on day of randomization to the postweaning diets for those mice derived from low vs. normal folate dams or for those mice randomized to low- or high-fat diets post-weaning (p = 0.828 and p = 0.542 respectively, Fig. 2)
Summary
The developmental origins of health and disease (DOHaD) hypothesis proposes that exposures during early life mod-. The “predictive adaptive response” hypothesis proposes that mismatch between the environment anticipated by the fetus, based on early (in utero) environmental exposures,. Molecular Nutrition & Food Research published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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