Risk factors in development of noncommunicable disease in fetal malnutrition-induced thrifty phenotype rats

Abstract

Born with a thrifty phenotype due to undernutrition during the prenatal period are thought to be at increased risk of developing diseases due to a mismatch between the acquired constitution and the nutritional environment after birth. However, the details of the thrifty phenotype are not clear. Therefore, we generated low birth weight model rats (LBW) which delivered from dams fed an energy-restricted low carbohydrate diet during the gestational period. We clarified that increased miR-322 causes the decrease in the expression of growth hormone (GH) receptors in the liver of LBW-non catchup growth rats. Furthermore, we revealed that LBW maintains the higher blood corticosterone levels after restraint stress exposure. We then found that increased expression of Gas5 lncRNA in the pituitary inhibits glucocorticoid-induced expression of miR-449a. Thus, we proposed that is one of the causes of impaired negative feedback regulation of glucocorticoids in the pituitary. Furthermore, we have shown the possibility that the skeletal muscle of LBW is easy-to-lose, and adipose tissue is hard-to-burn from the fasting-refeeding experiment. Thus, the thrifty phenotype of model rats has a body composition similar to sarcopenic obesity. It was suggested that these changes in body constitution might form the noncommunicable disease onset risk of the disease.