SAT-243 Investigation of Intervention Effect on Thrifty Phenotype of Low Birth Weight Rat

[OBJECTIVES] Low birthweight infants caused by fetal malnutrition acquire a thrifty phenotype, according to the development of health and disease (DOHaD) theory. When these children grow in a eutrophic environment, there is a mismatch of phenotype and environment, and it becomes a risk of various metabolic diseases. We aimed to develop an interventional method by creating a rat model exhibiting hyperinsulinemia with low birth weight due to low carbohydrate & calorie restriction during pregnancy and high fat diet (HFD) exposure after growth. Since metaborome analysis of rat blood revealed various metabolic changes, we investigated whether insulin resistance caused by mismatch is improved by methyl donor supplementation. [METHODS] Pups were obtained from mother rats fed with low carbohydrate & calorie restriction diet (LC) for the entire pregnancy period. For control, we used pups from mother rats who had fed standard diet (SC) ad libitum. We made a methyl donor diet in accordance with the previous report and fed ad libitum to mothers who were 3rd trimester of gestational period or breastfeeding. The male rats were divided into an HFD group and SC group at 4 weeks of age, and the HFD group rats were exposed to HFD for 18 weeks. Then, oral glucose tolerance test was carried out to examine blood glucose level, blood insulin concentration, and the expression analysis of mRNA in the liver after an overnight fast. [Results] HFD-exposed LC rats did not cause abrupt change in body weight or in body fat mass induce by HFD exposure even if supplementation to methyl donor was given to lactating maternal rat after giving birth. The blood insulin concentration after oral glucose loading which was high in the HFD-exposed LC rats, was reduced by methyl donor supplementation. In addition, the expression of elevated in FOXO1 and decreased in insulin receptor in the HFD-exposed liver was normalized with supplementation with methyl donor to the LC rats. [Conclusion] Supplementation of pregnant or postnatal methyl donor caused metabolic changes, normalizing abnormalities in the regulation of gene expression in the liver of low birth weight rats.