Effect of maternal diet on offspring metabolic programming: changes induced by carbohydrate quality

Abstract

Background Maternal diet and gestational diabetes have important implications for offspring health and disease. The fat mass and obesity associated gene (FTO) has the strongest relationship to increased body fat mass in humans, potentially via its effect on appetite and insulin sensitivity. Leptin plays a key role in regulating energy intake and expenditure, including appetite and hunger. Our hypothesis was that the expression of the Fto and leptin gene is influenced by the quality of carbohydrate in the maternal diet. Aim To compare glucose metabolism and mRNA expression of the Fto, leptin and other appetite-regulating genes in hypothalamic, adipose and/or other tissues of offspring of female mice fed high vs. low GI starch diets throughout pregnancy. Female C57BL/6 mice were randomly assigned to a low GI, high GI diet, or standard chow from 4 weeks of age and then mated with males who were fed the standard chow. In Study 1, male pups were weaned at the end of postnatal week 4 and divided into 2 subgroups, one following the chow diet and one their mother’s diet until 20 weeks of age. At week 20, the pups were sacrificed for tissue collection. In Study 2, female mice were sacrificed at gestation day 16-18 and placentas recovered. Tissues were analysed for gene expression and histological findings. Results Fto gene expression in the hypothalamus of offspring fed high GI starch from conception to postnatal week 20 was 2.5-fold higher than those fed low GI starch for the same time period (p = 0.01). Placental Fto gene expression was 3.8-fold higher in mothers fed the high GI starch diet vs. the low GI diet (p = 0.0003). By contrast, both early life and life-long exposure to a high GI diet were associated with lower Fto gene expression in white muscle. In the visceral adipose tissue, leptin gene expression was 3.3-fold higher in offspring exposed to the low GI diet from conception to week 20 and 4.4-fold higher in the offspring exposed to the low GI diet in early life. Plasma levels of the ‘hunger’ hormone ghrelin were significantly lower in offspring who received the low GI diet throughout life, while levels of the ‘satiety’ hormone leptin were higher. The co-expression of hypothalamic appetite genes AGRP/NPY and POMC/CART was also differentially regulated by the nature of the dietary carbohydrates. In this study, differences in diet, gene expression and hormone levels were not accompanied by differences in phenotype. Conclusion Carbohydrate quality, specifically the GI and/or rate of starch digestion in maternal diets, can differentially regulate the expression of the Fto and leptin gene in offspring tissues even in the absence of phenotypic differences. The nature of the dietary carbohydrates can regulate the co-expression of AGRP/NPY and POMC/CART in the hypothalamus. The findings imply that epigenetic changes induced in early life underlie observed differences in fat mass and insulin resistance in previous studies of high vs. low GI feeding. It is possible that changes in the nature of the carbohydrate in human diets may explain in part the current epidemic of obesity in children and adults.