Abstract
Maternal obesity increases the risk of metabolic dysregulation in rodent offspring, especially when offspring are exposed to a high-fat (HF), obesogenic diet later in life. We previously demonstrated that maternal choline supplementation (MCS) in HF-fed mouse dams during gestation prevents fetal overgrowth and excess adiposity. In this study, we examined the long-term metabolic influence of MCS. C57BL/6J mice were fed a HF diet with or without choline supplementation prior to and during gestation. After weaning, their pups were exposed to either a HF or control diet for 6 weeks before measurements. Prenatal and post-weaning dietary treatments led to sexually dimorphic responses. In male offspring, while post-weaning HF led to impaired fasting glucose and worse glucose tolerance (p < 0.05), MCS in HF dams (HFCS) attenuated these changes. HFCS (versus maternal normal fat control) appeared to improve metabolic functioning of visceral adipose tissue during post-weaning HF feeding, preventing the elevation in leptin and increasing (p < 0.05) mRNA expression of insulin receptor substrate 1 (Irs1) that promotes peripheral insulin signaling in male offspring. In contrast, MCS had minimal effects on metabolic outcomes of female offspring. In conclusion, MCS during HF feeding in mice improves long-term blood glucose homeostasis in male offspring when they are faced with a postnatal obesogenic environment.
Highlights
In the US, over 60% of women in their reproductive age are overweight or obese [1]
Maternal and post-weaning diets interacted to affect food and calorie intakes during the 6-week post-weaning feeding in both male and female offspring (p < 0.05). For both male and female offspring, post-weaning HF (PWHF) feeding decreased food intake compared to PWNF (p < 0.001)
We further investigated differential gene expression in the visceral adipose tissue in these offspring, including the expression of Lep, Pparg and insulin receptor substrate 1 (Irs1) which enhance insulin signaling in white adipose tissue (WAT), Retn which enhances liver glucose output and is elevated during obesity, retinol binding protein 4 (Rbp4) which inhibits liver insulin action, and Glut4 which is the transporter that mediates blood glucose uptake into adipocytes in response to insulin
Summary
In the US, over 60% of women in their reproductive age are overweight or obese [1]. Maternal obesity increases the risk of metabolic abnormalities during pregnancy, such as gestational diabetes mellitus (GDM), resulting in fetal overgrowth or macrosomia at birth, and exerts long-lasting impacts on the offspring, increasing their risks for obesity, diabetes, and other cardio-metabolic diseases in adulthood [1,2].Nutrients 2020, 12, 144; doi:10.3390/nu12010144 www.mdpi.com/journal/nutrientsMaternal dietary intakes provide an opportunity to overcome the negative influence of maternal obesity and a postnatal obesogenic environment on offspring health. Choline is a versatile semi-essential nutrient contained in eggs, meat, beans, and other foods. It participates in lipid metabolism, membrane structure maintenance, methyl group donation, and cellular signaling [3]. We previously reported that choline supplementation during pregnancy prevented fetal overgrowth and alleviated excess adiposity in high-fat (HF) fed mouse dams that were obese and glucose intolerant [4,5]. We proposed a mechanism where choline supplementation during maternal obesity and GDM reduced macronutrient anabolism and glucose/fat transport to the fetus by mitigating the mTOR (mechanistic target of rapamycin) signaling pathway in the placenta, leading to reduced fetal overgrowth [4]. Choline supplemented fetuses had lower hepatic mRNA expression of acetyl-CoA carboxylase 1 (Acc1), fatty acid desaturase
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