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Prenatal Choline Supplementation during High-Fat Feeding Improves Long-Term Blood Glucose Control in Male Mouse
Hunter W Korsmo1,2, Kaydine Edwards2, Bhoomi Dave2
1PhD Program in Biochemistry, The Graduate Center CUNY (City University of New York), New York, NY 10016, USA.
Insights
Maternal choline supplementation in mice fed a high-fat diet improves blood glucose control in male offspring. This prenatal intervention protected against metabolic dysfunction when pups were later exposed to an obesogenic diet.
Area of Science:
- Metabolic health
- Developmental programming
- Nutritional science
Background:
- Maternal obesity is linked to offspring metabolic dysregulation, particularly with postnatal high-fat (HF) diet exposure.
- Previous research showed maternal choline supplementation (MCS) in HF-fed dams prevents fetal overgrowth and adiposity.
- The long-term metabolic effects of MCS require further investigation.
Purpose of the Study:
- To examine the long-term metabolic impact of maternal choline supplementation (MCS) on offspring.
- To investigate the sexually dimorphic effects of prenatal diet and postnatal diet on metabolic health.
- To determine if MCS can mitigate metabolic dysfunction in offspring exposed to a high-fat diet.
Main Methods:
- Mice dams were fed a high-fat (HF) diet with or without choline supplementation (MCS) during gestation.
- Offspring were weaned and exposed to either a HF or control diet for 6 weeks.
- Metabolic parameters including fasting glucose, glucose tolerance, and adipose tissue gene expression were measured.
Main Results:
- Postnatal HF diet impaired fasting glucose and glucose tolerance in male offspring.
- MCS in HF dams (HFCS) attenuated these negative metabolic changes in males.
- HFCS improved visceral adipose tissue function in males, preventing leptin elevation and increasing insulin receptor substrate 1 (Irs1) mRNA expression.
- MCS had minimal impact on metabolic outcomes in female offspring.
Conclusions:
- Maternal choline supplementation during high-fat feeding in mice improves long-term blood glucose homeostasis in male offspring.
- The benefits of MCS appear specific to males when facing a postnatal obesogenic environment.
- This study highlights the potential of prenatal nutrition to influence offspring metabolic health in a sex-specific manner.
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.
