Long-term effects of pro-opiomelanocortin methylation induced in food-restricted dams on metabolic phenotypes in male rat offspring

Abstract

Objective Maternal malnutrition affects the growth and metabolic health of the offspring. Little is known about the longterm effect on metabolic indices of epigenetic changes in the brain caused by maternal diet. Thus, we explored the effect of maternal food restriction during pregnancy on metabolic profiles of the offspring, by evaluating the DNA methylation of hypothalamic appetite regulators at 3 weeks of age. Methods Sprague-Dawley rats were divided into 2 groups: a control group and a group with a 50% food-restricted (FR) diet during pregnancy. Methylation and expression of appetite regulator genes were measured in 3-week-old offspring using pyrosequencing, real-time polymerase chain reaction, and western blotting analyses. We analyzed the relationship between DNA methylation and metabolic profiles by Pearson's correlation analysis. Results The expression of pro-opiomelanocortin (POMC) decreased, whereas DNA methylation significantly increased in male offspring of the FR dams, compared to the male offspring of control dams. Hypermethylation of POMC was positively correlated with the levels of high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol in 3-week-old male offspring. In addition, there were significant positive correlations between hypermethylation of POMC and the levels of triglycerides, HDL-C, and leptin in 6-month-old male offspring. Conclusion Our findings suggest that maternal food restriction during pregnancy influences the expression of hypothalamic appetite regulators via epigenetic changes, leading to the development of metabolic disorders in the offspring. © 2020 Korean Society of Obstetrics and Gynecology.