Abstract
Maternal diet and gestational hyperglycaemia have implications for offspring health. Leptin (LEP) and fat mass and obesity-associated (FTO) alleles are known to influence body fat mass in humans, potentially via effects on appetite. We hypothesized that expression of Fto, Lep, and other appetite-related genes (Argp, Npy, Pomc, Cart, Lepr) in the offspring of female mice are influenced by the glycaemic index (GI) of carbohydrates in the maternal diet. C57BL/6 mice were randomly assigned to low or high GI diets and mated with chow-fed males at eight weeks of age. Male pups were weaned at four weeks and randomly divided into two groups, one group following their mother’s diet (LL and HH), and one following the standard chow diet (LC and HC) to 20 weeks. Fto expression was 3.8-fold higher in the placenta of mothers fed the high GI diet (p = 0.0001) and 2.5-fold higher in the hypothalamus of 20-week old offspring fed the high GI (HH vs. LL, p < 0.0001). By contrast, leptin gene (Lep) expression in visceral adipose tissue was 4.4-fold higher in four-week old offspring of low GI mothers (LC vs. HC, p < 0.0001) and 3.3-fold higher in visceral adipose tissue of 20-week old animals (LL vs. HH, p < 0.0001). Plasma ghrelin and leptin levels, and hypothalamic appetite genes were also differentially regulated by maternal and offspring diet. These findings provide the first evidence in an animal model that maternal high GI dietary carbohydrates that are digested and absorbed faster may contribute to programming of appetite in offspring.
Highlights
Obesity and type 2 diabetes have increased globally over recent decades and appear at increasingly younger ages [1]
Maternal glucose levels that are in the high-normal range but below the diagnostic values of gestational diabetes are associated with increased birth weight and high foetal insulin levels [4,5]
Using the rate of digestion in vitro as a surrogate, we confirmed that the custom high glycaemic index (GI) diet contained more rapidly digestible starch than the low GI diet
Summary
Obesity and type 2 diabetes have increased globally over recent decades and appear at increasingly younger ages [1]. Maternal obesity and gestational diabetes are associated with higher birthweight and foetal adiposity [2]. Foetal metabolism is largely based on the principal energy substrate, glucose [3], which is transported across the placenta at the same glucose concentration as the maternal circulation. Maternal glucose levels that are in the high-normal range but below the diagnostic values of gestational diabetes are associated with increased birth weight and high foetal insulin levels [4,5]. In normal pregnancy and those affected by gestational diabetes, dietary interventions that reduce postprandial glycaemia, including low glycaemic index (GI) diets, have been associated with improved pregnancy outcomes [6,7,8,9,10].
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