Prenatal Choline and Betaine Differentially Program Adult Hepatic One-Carbon Metabolism in Wistar Rats

Area of Science:

• Nutritional Biochemistry
• Developmental Biology
• Metabolomics

Background:

• Choline and betaine are vital methyl donors for one-carbon metabolism during development.
• Prenatal exposure effects on offspring hepatic metabolites and methyltransferase expression are not fully understood.

Purpose of the Study:

• To investigate the prenatal effects of choline and betaine supplementation on Wistar rat offspring's hepatic metabolites and methyltransferase expression.
• To elucidate the nutrient-specific programming of one-carbon metabolism.

Main Methods:

• Gestational supplementation with choline or betaine in Wistar rats.
• Analysis of offspring body weight, food intake, adipose mass, and hepatic metabolites.
• Measurement of methyltransferase gene expression (Dnmt1, PNMT).
• Kinetic modeling and Regularized Canonical Correlation Analysis (RCCA).

Main Results:

• Supplementation reduced offspring body weight, food intake, and adipose mass.
• Both nutrients increased hepatic glycerophosphocholine; betaine also elevated sphingomyelin and dimethylglycine.
• Choline and betaine increased hepatic S-adenosylmethionine (SAM), particularly in males.
• Betaine upregulated Dnmt1 and PNMT in females, while males showed broader methyltransferase responses.
• Kinetic modeling highlighted SAM availability's role; RCCA revealed sex-specific metabolic modules.

Conclusions:

• Gestational choline and betaine supplementation differentially program offspring hepatic one-carbon metabolism.
• Findings underscore the distinct metabolic roles of choline and betaine in early development.
• Sex-specific responses in methyltransferase expression and metabolic networks were observed.