Differential methylation in glucoregulatory genes of offspring born before vs. after maternal gastrointestinal bypass

Frédéric Guénard1, Yves Deshaies, Katherine Cianflone

  • 1Institute of Nutrition and Functional Foods and Department of Food Science and Nutrition, Laval University, Quebec City, QC G1V 0A6, Canada.

Insights

Maternal weight loss surgery significantly impacts offspring cardiometabolic health. Children born after surgery show improved metabolic profiles due to lasting changes in their gene methylation and expression.

Area of Science:

  • Epigenetics
  • Metabolic Health
  • Pregnancy Research

Background:

  • Maternal obesity and overnutrition during pregnancy can program adult disease risk in offspring.
  • Children born after maternal bariatric surgery (AMS) have lower obesity rates and better cardiometabolic profiles than siblings born before surgery (BMS).

Purpose of the Study:

  • To investigate the impact of maternal weight loss surgery on gene methylation in offspring.
  • To identify biological pathways associated with improved cardiometabolic health in children born after maternal bariatric surgery.

Main Methods:

  • Differential methylation analysis was performed on a sibling cohort of 25 BMS and 25 AMS offspring (ages 2-25) from 20 mothers.
  • Gene methylation and expression levels were correlated with plasma markers of insulin resistance (fasting insulin, homeostasis model of insulin resistance).

Main Results:

  • 5,698 genes showed differential methylation between BMS and AMS siblings, particularly those involved in glucose regulation, inflammation, and vascular disease.
  • Correlations between gene methylation, expression, and insulin resistance markers supported metabolic improvements in AMS offspring.
  • Findings indicate durable epigenetic and transcriptomic changes in offspring following maternal weight loss surgery.

Conclusions:

  • Maternal weight loss surgery leads to lasting, detectable changes in the offspring's methylome and transcriptome.
  • These epigenetic modifications are linked to improved cardiometabolic health and reduced insulin resistance in children born after maternal bariatric surgery.