Abstract

Excess vitamin intake during pregnancy leads to obesogenic phenotypes, and folic acid accounts for many of these effects in male, but not in female, offspring. These outcomes may be modulated by another methyl nutrient choline and attributed to the gut microbiota. Pregnant Wistar rats were fed an AIN-93G diet with recommended vitamin (RV), high 10-fold multivitamin (HV), high 10-fold folic acid with recommended choline (HFol) or high 10-fold folic acid without choline (HFol-C) content. Male and female offspring were weaned to a high-fat RV diet for 12 weeks post-weaning. Removing choline from the HFol gestational diet resulted in obesogenic phenotypes that resembled more closely to HV in male and female offspring with higher body weight, food intake, glucose response to a glucose load and body fat percentage with altered activity, concentrations of short-chain fatty acids and gut microbiota composition. Gestational diet and sex of the offspring predicted the gut microbiota differences. Differentially abundant microbes may be important contributors to obesogenic outcomes across diet and sex. In conclusion, a gestational diet high in vitamins or imbalanced folic acid and choline content contributes to the gut microbiota alterations consistent with the obesogenic phenotypes of in male and female offspring.

Highlights

  • Inadequate or excess nutrient intake during pregnancy predisposes offspring to a greater risk of chronic diseases including obesity, type 2 diabetes, metabolic syndrome, cardiovascular disease and non-alcoholic fatty liver disease [1,2,3]

  • We have previously shown that feeding a high, non-toxic multivitamin (10-fold the recommended amount of multivitamins) AIN-93G diet during pregnancy produces obesogenic phenotypes in male [8] and female

  • The high multivitamin (HV), high 10-fold folic acid with recommended choline (HFol) and high folic acid without choline (HFol-C) groups had 12% higher body weight than the recommended vitamin (RV) group (Diet: p = 0.0002, Time: p < 0.0001, Diet ∗ Time Interaction: p < 0.0001; Figure 2A)

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Summary

Introduction

Inadequate or excess nutrient intake during pregnancy predisposes offspring to a greater risk of chronic diseases including obesity, type 2 diabetes, metabolic syndrome, cardiovascular disease and non-alcoholic fatty liver disease [1,2,3]. In the current pattern of over-consumption of nutrients, 77% of pregnant women are reported to use one or more dietary supplements contributing to vitamin intake levels above the recommendation [4]. We have previously shown that feeding a high, non-toxic multivitamin (10-fold the recommended amount of multivitamins) AIN-93G diet during pregnancy produces obesogenic phenotypes in male [8] and female [9] Wistar rat offspring. We identified folic acid as a vitamin candidate responsible for greater food intake, body weight, characteristics of metabolic syndrome and changes in hypothalamic feeding-related neuropeptide expression through. Female offspring born to dams fed a high folic acid diet had lower body weight [11], making unclear whether another nutrient factor modifies the effect of excess folic acid on metabolic disease risk

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