Choline prevents fetal overgrowth and normalizes placental fatty acid and glucose metabolism in a mouse model of maternal obesity

Abstract

Maternal obesity increases placental transport of macronutrients, resulting in fetal overgrowth and obesity later in life. Choline participates in fatty acid metabolism, serves as a methyl donor, and influences growth signaling, which may modify placental macronutrient homeostasis and affect fetal growth. Using a mouse model of maternal obesity, we assessed the effect of maternal choline supplementation on preventing fetal overgrowth and restoring placental macronutrient homeostasis. C57BL/6J mice were fed either a high-fat (HF, 60% kcal from fat) diet or a normal (NF, 10% kcal from fat) diet with a drinking supply of either 25 mM choline chloride or control purified water, respectively, beginning 4 weeks prior to mating until gestational day 12.5. Fetal and placental weight, metabolites, and gene expression were measured. HF feeding significantly (P < 0.05) increased placental and fetal weight in the HF-control (HFCO) versus NF-control (NFCO) animals, whereas the HF choline-supplemented (HFCS) group effectively normalized placental and fetal weight to the levels of the NFCO group. Compared to HFCO, the HFCS group had lower (P < 0.05) glucose transporter 1 (GLUT1) and fatty acid transport protein 1 (FATP1) expression as well as lower accumulation of glycogen in the placenta. The HFCS group also had lower (P < 0.05) placental 4E-binding protein 1 and ribosomal protein s6 phosphorylation, which are indicators of mechanistic target of rapamycin complex 1 (mTORC1) activation favoring macronutrient anabolism. In summary, our results suggest that maternal choline supplementation prevented fetal overgrowth in obese mice at mid-gestation and improved biomarkers of placental macronutrient homeostasis.

Exercise prevents the adverse effects of maternal obesity on placental vascularization and fetal growth

“…In the present study, we found that the expression of glutamine and amino acid transporters was down‐regulated, although fatty acid transporters were increased in HFD mice, consistent with a previous study (Nam et al . ). Nonetheless, the overall changes in the contents of nutrient transporters were quite small, suggesting that changes in nutrient transporter abundance might not explain the observed changes in placental function.…”

Prenatal Choline Supplementation during High-Fat Feeding Improves Long-Term Blood Glucose Control in Male Mouse Offspring

“…Male mice for mating received the NFCO diet. The composition of experimental diets was previously described by others [20,21] and we reported the total choline contents in these diets (11.7 mmol/kg in the HF diet and 7.6 mmol/kg in the NF diet) previously [4]. The 60% kcal HF diet was chosen based on our prior studies demonstrating stable phenotypes of obesity and glucose intolerance in dams [4].…”

“…Research has shown that choline supplementation during pregnancy alters fetal epigenetic programming, improves offspring cognitive development, and modifies placental vasculature and macronutrient transport in rodents or humans [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].…”

“…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]. Maternal choline supplementation (MCS) also appeared to downregulate the expression of lipogenic genes in the liver of fetuses from HF dams, serving as a plausible mechanism to reduce liver triglyceride accumulation in these fetuses [5].…”

Maternal Choline Intake Programs Hypothalamic Energy Regulation and Later‐Life Phenotype of Male Wistar Rat Offspring

“…Similarly, our previous studies found that high intakes (5–10 folds) of folic acid during pregnancy led to higher food intake, body weight gain, and other biomarkers of obesity in the adult offspring. [ 8,16 ] Although the potential protective effects of choline supplementation against obesity in the offspring has been reported by one study, [ 17 ] the effects were only explored in the offspring mid‐gestation, and long‐term postnatal effects of choline were not explored. Furthermore, obese female mice in that study were maintained on fourfold choline intakes for 4 weeks prior to mating and throughout gestation.…”