Choline and betaine alter fetal brain expression of genes related to docosahexaenoic acid availability in a mouse model of gestational diabetes

Abstract

Gestational diabetes mellitus (GDM) is associated with lower cord blood docosahexaenoic acid (DHA) concentrations, which can potentially delay brain development of affected infants. Phosphatidylcholine synthesized via the de novo pathway is enriched with DHA, thereby providing an available source of DHA. Using a mouse model of GDM, we assessed whether supplementation of dams with choline or its oxidative derivative, betaine, modified the expression of genes related to DHA availability in fetal brains. C57BL/6J female mice were fed a high‐fat diet (60% kcal from fat) six weeks before and throughout gestation to induce GDM‐like symptoms. The animals received 25 mM choline chloride, 1% betaine, or control drinking water until embryonic day 17.5. Fetal brain samples were collected for gene expression analysis. Betaine supplementation in the high‐fat fed dams increased the expression of fatty acid binding protein 7 (Fabp7), which transports DHA, and Fabp5, which transports saturated fatty acids in fetal brains. Choline supplementation did not alter the expression of Fabp genes. However, choline upregulated expression of phospholipase A2 (Pla2g6), which releases DHA from the middle position of the glycerol backbone of phospholipids such as phosphatidylcholine, enhancing availability of free DHA in the brain. Expression of arachidonate 15‐lipoxygenase, cyclooxygenase‐2, and brain‐derived neurotrophic factor were not altered by choline or betaine supplementation. Our results support a role for maternal choline or betaine supplementation in modifying DHA availability in fetal brain by altering gene expression in the offspring of GDM dams.Support or Funding InformationNIH, New York Academy of Sciences, PSC‐CUNY