Folate in a high multivitamin gestational diet causes obesogenic phenotype and epigenetic alterations in hypothalamic feeding pathways in Wistar rat offspring (271.3)

Abstract

High multivitamin (HV, 10‐fold AIN‐93G) gestational diets fed to Wistar rats produce offspring with higher food intake, obesity and characteristics of metabolic syndrome. The objective was to determine if folate within the HV diet contributes to obesogenic phenotype through epigenetic effects on hypothalamic regulatory mechanisms. Male offspring of dams fed HV diet with normal folate (NF) (HVNF) were compared with those from HV fed dams. Offspring were weaned to a high fat diet for 8 weeks. HVNF offspring had lower food intake (5%, P=0.0005), body weight (4%, P=0.03), fat preference (12%, P=0.02), adiposity index (10%, P=0.04), plasma leptin concentration (24%, P=0.03), glucose response to a glucose load (18%, P<0.05) and insulin resistance (12%, P=0.03). They had higher pro‐opiomelanocortin (POMC; 38%, P<0.05) and lower leptin receptor (Ob‐Rb; 10%, P=0.03), mammalian target of rapamycin (MTOR; 7%, P=0.01), serotonin receptor (5‐HTR) 1A (11%, P=0.03) and 5‐HTR2A (21%, P=0.03) gene expression. DNA methylation of 5‐HTR1A (P=0.0007) was lower but higher in 5‐HTR2A (P=0.01). Phosphoinositide 3‐kinase (PI3K) signaling protein expression was improved (42%, P=0.03). In conclusion, folate in the HV gestational diet contributes to the obesogenic phenotype in the offspring concurrent with alterations in gene expression, DNA methylation and energy sensing in the hypothalamus that favor increased food intake.Grant Funding Source: Supported by Canadian Institutes of Health Research, Institute of Nutrition, Metabolism and Diabetes