Choline and Folic Acid in Diets Consumed during Pregnancy Interact to Program Food Intake and Metabolic Regulation of Male Wistar Rat Offspring

• Published in: The Journal of nutrition 2021-04, Vol.151 (4), p.857-865
• Main Authors: Hammoud, Rola, Pannia, Emanuela, Kubant, Ruslan, Wasek, Brandi, Bottiglieri, Teodoro, Malysheva, Olga V, Caudill, Marie A, Anderson, G Harvey
• Format: Article
• Language: English
• Subjects: Animal Nutritional Physiological Phenomena; Animals; Animals, Newborn; Appetite Regulation - physiology; Betaine; Body weight; Body Weight - physiology; Body weight gain; Brain; Brain - metabolism; Carbon; Choline; Choline - administration & dosage; Choline - blood; Diet; Eating - physiology; Energy metabolism; Female; fetal programming; Folic acid; Folic Acid - administration & dosage; Folic Acid - blood; Food; Food intake; Gene Expression; Gene sequencing; Homocysteine; Hormones; Hypothalamus; Hypothalamus - metabolism; in utero; Insulin; Insulin - blood; Intra-Abdominal Fat - anatomy & histology; Juveniles; Leptin; Leptin - blood; Male; Males; Maternal Nutritional Physiological Phenomena; Maternal-Fetal Exchange - physiology; Metabolism; Metabolites; Methionine; Models, Animal; Neonates; Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions; Nutrients; Obesity; Offspring; one-carbon cycle; Phenotypes; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Ribonucleic acid; RNA; Rodents; Vitamin B; Weaning
• ISSN: 0022-3166; 1541-6100
• DOI: 10.1093/jn/nxaa419

North American women consume high folic acid (FA), but most are not meeting the adequate intakes for choline. High-FA gestational diets induce an obesogenic phenotype in rat offspring. It is unclear if imbalances between FA and other methyl-nutrients (i.e., choline) account for these effects. This study investigated the interaction of choline and FA in gestational diets on food intake, body weight, one-carbon metabolism, and hypothalamic gene expression in male Wistar rat offspring. Pregnant Wistar rats were fed an AIN-93G diet with recommended choline and FA [RCRF; 1-fold, control] or high (5-fold) FA with choline at 0.5-fold [low choline and high folic acid (LCHF)], 1-fold [recommended choline and high folic acid (RCHF)], or 2.5-fold [high choline and high folic acid (HCHF)]. Male offspring were weaned to an RCRF diet for 20 wk. Food intake, weight gain, plasma energy-regulatory hormones, brain and plasma one-carbon metabolites, and RNA sequencing (RNA-seq) in pup hypothalamuses were assessed. Adult offspring from LCHF and RCHF, but not HCHF, gestational diets had 10% higher food intake and weight gain than controls (P < 0.01). HCHF newborn pups had lower plasma insulin and leptin compared with LCHF and RCHF pups (P < 0.05), respectively. Pup brain choline (P < 0.05) and betaine (P < 0.01) were 22–33% higher in HCHF pups compared with LCHF pups; methionine was ∼23% lower after all high FA diets compared with RCRF (P < 0.01). LCHF adult offspring had lower brain choline (P < 0.05) than all groups and lower plasma 5-methyltetrahydrofolate (P < 0.05) than RCRF and RCHF groups. HCHF adult offspring had lower plasma cystathionine (P < 0.05) than LCHF adult offspring and lower homocysteine (P < 0.01) than RCHF and RCRF adult offspring. RNA-seq identified 144 differentially expressed genes in the hypothalamus of HCHF newborns compared with controls. Increased choline in gestational diets modified the programming effects of high FA on long-term food intake regulation, plasma energy-regulatory hormones, one-carbon metabolism, and hypothalamic gene expression in male Wistar rat offspring, emphasizing a need for more attention to the choline and FA balance in maternal diets.