Obesogenic phenotype of offspring of dams fed a high multivitamin diet is prevented by a post-weaning high multivitamin or high folate diet

• Published in: International Journal of Obesity 2013-09, Vol.37 (9), p.1177-1182
• Main Authors: Cho, C E, Sánchez-Hernández, D, Reza-López, S A, Huot, P S P, Kim, Y-I, Anderson, G H
• Format: Article
• Language: English
• Subjects: 631/208/199; 631/443/319/1488/1562; 692/699/2743/393; 692/700/459/1994; Animals; Animals, Newborn; Biological and medical sciences; Biomarkers - metabolism; Body Weight; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - metabolism; Chronic illnesses; Deoxyribonucleic acid; Diet; DNA; DNA methylation; Eating - genetics; Epidemiology; Epigenetics; Feeding Behavior; Female; Folic acid; Folic Acid - administration & dosage; Folic Acid - metabolism; Folic Acid - pharmacology; Food; Gene expression; Gene Expression Regulation, Developmental; Genotype & phenotype; Glucose; Health Promotion and Disease Prevention; Hypothalamus; Hypothalamus - metabolism; Hypotheses; Internal Medicine; Male; Maternal Nutritional Physiological Phenomena - genetics; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Metabolic disorders; Metabolic syndrome; Metabolic Syndrome - etiology; Metabolic Syndrome - genetics; Metabolic Syndrome - metabolism; Multivitamins; Neuropeptides; Obesity; Obesity - etiology; Obesity - genetics; Obesity - metabolism; Offspring; original-article; Phenotype; Physiological aspects; Pregnancy; Prevention and actions; Pro-Opiomelanocortin - metabolism; Public Health; Public health. Hygiene; Public health. Hygiene-occupational medicine; Rats; Rats, Wistar; Receptor, Insulin - metabolism; Receptors, Dopamine - metabolism; Receptors, Leptin - metabolism; Receptors, Serotonin; Sucrose; Vitamin B; Vitamins - administration & dosage; Vitamins - pharmacology; Weaning
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/ijo.2012.210

Background: High multivitamin (10-fold AIN-93G, HV) diets fed during pregnancy to Wistar rats increase characteristics of metabolic syndrome in offspring when weaned to the recommended vitamin (RV) diet. Objective: To determine whether the effects of HV gestational diets on obesogenic phenotypes in the offspring arise as a consequence of altered hypothalamic control of feeding behavior and if their increased food intake could be prevented by feeding them HV or high folate (10-fold folate, HFol) diets. Methods: Male offspring of dams fed HV diet during pregnancy weaned to RV, HV or HFol diets were compared with those born to RV dams and weaned to RV diet for 29 weeks. Food intake over 72 h and body weight were measured bi-weekly and weekly, respectively. Glucose response to a glucose load was measured at 18 weeks post weaning. Hypothalamic gene expression of feeding-related neuropeptides including neuropeptide Y, pro-opiomelanocortin (POMC), insulin receptor, leptin receptor, brain-derived neurotrophic factor (BDNF), receptors for dopamine (DopaR1/2/5) and serotonin (SeroR1A/2A/2C), as well as global DNA methylation and brain and plasma folate concentrations were measured at 29 weeks post weaning. Results: HV or HFol pup diets increased brain and plasma folate concentrations and prevented the increase in food intake (5%, P =0.03), body weight (8%, P =0.0006) and glucose response to a glucose load (36%, P =0.02) found in those fed the RV diet. Expression of anorexigenic POMC ( P =0.004) and BDNF ( P =0.02) was higher, and DopaR1 was lower ( P =0.06) in pups fed the HV diet. The HFol pup diet partially brought BDNF to the control level ( P =0.02) and lowered SeroR2A ( P =0.008). Expression of other genes was unaffected. Global DNA methylation was similar among the diet groups. Conclusion: The obesogenic phenotype in offspring from HV-fed dams is prevented by feeding HV or HFol pup diets, possibly due to post-weaning modulation of food intake regulatory mechanisms. Editor's Note: This paper reports that the offspring of pregnant rats given excess multivitamins (10 times normal requirements) become more obese later in life than control animals whose mothers were given normal vitamin doses. Although this is an animal study, it is worth considering the implications for humans. A tendency to take more of a medication than is prescribed is common. Some pregnant women consume higher than usual doses of vitamins during their pregnancy and the possibility exists that