Choline Supplementation Normalizes Fetal Adiposity and Reduces Lipogenic Gene Expression in a Mouse Model of Maternal Obesity

Abstract

Maternal obesity increases fetal adiposity which may adversely affect metabolic health of the offspring. Choline regulates lipid metabolism and thus may influence adiposity. This study investigates the effect of maternal choline supplementation on fetal adiposity in a mouse model of maternal obesity. C57BL/6J mice were fed either a high-fat (HF) diet or a control (NF) diet and received either 25 mM choline supplemented (CS) or control untreated (CO) drinking water for 6 weeks before timed-mating and throughout gestation. At embryonic day 17.5, HF feeding led to higher (p < 0.05) percent total body fat in fetuses from the HFCO group, while the choline supplemented HFCS group did not show significant difference versus the NFCO group. Similarly, HF feeding led to higher (p < 0.05) hepatic triglyceride accumulation in the HFCO but not the HFCS fetuses. mRNA levels of lipogenic genes such as Acc1, Fads1, and Elovl5, as well as the transcription factor Srebp1c that favors lipogenesis were downregulated (p < 0.05) by maternal choline supplementation in the HFCS group, which may serve as a mechanism to reduce fat accumulation in the fetal liver during maternal HF feeding. In summary, maternal choline supplementation improves indices of fetal adiposity in obese dams at late gestation.

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

“…However, neither HF feeding nor choline supplementation during the prenatal period alone modified blood glucose control in the postnatal life. This observation was consistent with our previous studies of fetuses exposed to the same maternal feeding model, where HFCS dams prevented fetal overgrowth in mid-gestation [4] and reduced fetal adiposity in late-gestation [5], while HF alone led to fetal overgrowth and excess adiposity, and that choline supplementation in the normal fat (control) environment had no impact on growth or adiposity. Our findings demonstrate for the first time that the metabolism-modifying effect of choline supplementation under the maternal HF condition seems to be maintained throughout the prenatal and postnatal period in male offspring.…”

“…As mentioned in Materials and Methods, we chose the 60% kcal fat diet since it can stably induce the obesity and GDM phenotypes in dams and offspring. In our previous studies using the same 60% kcal HF diet to examine its influence on fetal growth, we found higher fetal weight in mid-gestation and greater fetal whole-body adiposity in late gestation [4,5]. These observations suggest that the faltering in the growth of HFCO offspring likely occurred during lactation.…”

“…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 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]. Specifically, choline supplemented fetuses had lower hepatic mRNA expression of acetyl-CoA carboxylase 1 (Acc1), fatty acid desaturase 1 (Fads1), and ELOVL fatty acid elongase 5 (Elovl5), as well as sterol regulatory element-binding transcription factor 1 (Srebf1), which activates the transcription of lipogenic genes, when compared to unsupplemented HF fetuses [5].…”

“…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]. Specifically, choline supplemented fetuses had lower hepatic mRNA expression of acetyl-CoA carboxylase 1 (Acc1), fatty acid desaturase 1 (Fads1), and ELOVL fatty acid elongase 5 (Elovl5), as well as sterol regulatory element-binding transcription factor 1 (Srebf1), which activates the transcription of lipogenic genes, when compared to unsupplemented HF fetuses [5]. It is unclear whether these alterations in fetal liver gene expression by maternal choline supplementation can be maintained into adulthood and influence long-term metabolic health of the offspring.…”