High Choline During Pregnancy Reduces Characteristics of the Metabolic Syndrome in Male Wistar Rat Offspring Fed a High Fat Post-Weaning Diet

Abstract

ObjectivesThe prenatal period is a critical time for fetal development, programming the offspring’s later-life health in response to the postnatal environment. We have shown that a high maternal choline diet programs long-term energy regulation leading to higher food intake and weight-gain in mature rat offspring fed a normal fat diet. However, the offspring’s response to an obesogenic post-weaning diet has not been described. We aim to elucidate the interaction between the choline content of the gestational diet (GD) and fat content of the post-weaning diet (PWD) on male Wistar rat offspring’s long-term metabolic phenotype. MethodsPregnant Wistar rats were fed an AIN-93G diet with either recommended choline (RC, 1g/kg diet choline bitartrate) or high choline (HC, 2.5-fold). Male pups were weaned to either a normal (10%) fat (RC-NF and HC-NF) or a high (45%) fat (RC-HF and HC-HF) diet for 17 weeks. Dependent measures were body weight, food intake, visceral adiposity, plasma glucoregulatory hormones and triglycerides, and plasma and hepatic free fatty acids (FFAs). Data were analyzed with 2-way ANOVA for main effects of GD and PWD and their interaction. Measures with significant interaction effects were followed by a Student’s T-test comparing groups stratified by PWD. ResultsHC-HF offspring had lower body weight (7%, P < 0.05), and visceral adiposity (15%, P < 0.05), but no difference in food intake compared to RC-HF. HC-HF offspring had lower insulin (18%, P < 0.05), HOMA-IR (24%, P < 0.01), and plasma triglycerides (30%, P < 0.05) but no difference in leptin. Total hepatic ω-3 FFAs (30%, P < 0.05) were higher and ω-6/ω-3 (P < 0.01) was lower in HC-HF compared to RC-HF, indicating an ameliorated metabolic phenotype in HC-HF offspring. In contrast, HC-NF offspring had higher food intake (8%, P < 0.01) and body weight (6%, P < 0.05) and no difference in adiposity compared to RC-NF. They also had higher plasma leptin adjusted for adiposity (22%, P < 0.05) but not insulin or HOMA-IR compared to RC-NF. Hepatic C16:1n-7/C16:0 ratio was higher in HC-NF compared to RC-NF, suggestive of dysregulated lipid metabolism. ConclusionsGestational choline supplementation is associated with improved long-term metabolic regulation in male Wistar rat offspring fed a high fat post-weaning diet. Funding SourcesCIHR-Institute of Nutrition, Metabolism, and Diabetes.