Maternal high fat diet and offspring CNS gene expression

Abstract

The goal of our research is to understand the molecular mechanisms that link maternal high fat diet consumption during pregnancy with altered CNS gene expression in the offspring. In our model, pregnant and lactating mouse dams are fed a high fat (HF) diet, and large for gestational age (LGA) offspring demonstrate significant dysfunction in the dopaminergic, and opioid systems. Prenatal diet can impact DNA methylation, and we have documented both global and gene‐specific methylation differences in LGA mice. Dietary methionine is essential for proper DNA methylation, and we hypothesized that methyl supplementation of the HF diet would prevent some of the aberrant DNA methylation/gene expression in the LGA offspring. Offspring from dams fed a HF diet show increased dopamine transporter expression in the brain. However, when both control and HF diet were supplemented with methyl donors, this effect is blocked. The pattern of responses is also affected by offspring sex. These data show that methyl donor supplementation can reverse aberrant gene expression changes in LGA offspring, and support the examination of this intervention on methylation and gene expression changes in the CNS of LGA animals.