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

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.

Maternal Choline Supplementation and High-Fat Feeding Interact to Influence DNA Methylation in Offspring in a Time-Specific Manner

“…In this study, we examined liver histopathology after the 6-week post-weaning HF feeding, but did not find any sign of steatosis or inflammation in the samples from different groups (Supplementary Figure 3). Post-weaning HF feeding for 6 weeks increased VAT adipocyte size, yet this increase was prevented in the prenatal HFCS group (Figure 1), consistent with the lower leptin secretion implicated with CS compared to other post-weaning HF groups as we previously reported (17).…”

“…We earlier described that maternal HF feeding led to higher fetal whole body adiposity and hepatic triglycerides while maternal CS mitigated these adverse alterations at E17.5 (16). In male offspring who received CS during prenatal HF feeding (i.e., the HFCS group), there was no difference in weight gain yet improved blood glucose control compared to the control group after 6-week post-weaning HF feeding (17). In this study, we examined liver histopathology after the 6-week post-weaning HF feeding, but did not find any sign of steatosis or inflammation in the samples from different groups (Supplementary Figure 3).…”

“…Moreover, when the offspring are also exposed to a postnatal obesogenic environment, their risks of adverse metabolic outcomes such as glucose intolerance and hepatic steatosis are further exacerbated (9)(10)(11)(12)(13)(14). We have previously found that maternal CS reduced the negative effects of maternal HF-induced obesity and gestational diabetes, normalizing fetal growth, preventing excess in fetal adiposity, and reducing glucose intolerance of offspring when they were exposed to an obesogenic diet after birth (15)(16)(17). It remains to be determined whether these observed phenotypic benefits were mediated in part by the influence of maternal CS on epigenetic programming.…”

High Choline Intake during Pregnancy Reduces Characteristics of the Metabolic Syndrome in Male Wistar Rat Offspring Fed a High Fat But Not a Normal Fat Post-Weaning Diet

“…These results are consistent with those showing a protective effect of choline supplementation (4.5-fold) to a HF diet prior to conception and throughout gestation in mice on the offspring’s metabolic phenotype [ 9 , 15 ]. However, they contrast with our previous studies exploring other methyl vitamins, showing that a diet containing 10-fold vitamins B6, B12, and folic acid during pregnancy associated with higher food intake and body weight in male offspring fed a HF PWD diet [ 16 ].…”

“…Because the North American diet averages around 36% fat [ 8 ], investigating the effect of choline supplementation during pregnancy on the offspring’s long-term metabolic response to a HF diet is timely and relevant. One recent report in mice identified a protective effect of choline when increased 4.5-fold in a 60% fat diet fed to mice 4 weeks before mating and throughout pregnancy on the development of obesity in the offspring maintained on a 60% fat diet [ 9 ]. However, the potential protective effect of moderate physiologically relevant choline intakes (2.5-fold) only during pregnancy on the offspring’s long-term metabolic response to a HF PWD has not been fully explored.…”