title: Differential methylation in glucoregulatory genes of offspring born before vs. after maternal gastrointestinal bypass surgery.
abstract: Obesity and overnutrition during pregnancy affect fetal programming of adult disease. Children born after maternal bariatric gastrointestinal bypass surgery (AMS) are less obese and exhibit improved cardiometabolic risk profiles carried into adulthood compared with siblings born before maternal surgery (BMS). This study was designed to analyze the impact of maternal weight loss surgery on methylation levels of genes involved in cardiometabolic pathways in BMS and AMS offspring. Differential methylation analysis between a sibling cohort of 25 BMS and 25 AMS (2-25 y-old) offspring from 20 mothers was conducted to identify biological functions and pathways potentially involved in the improved cardiometabolic profile found in AMS compared with BMS offspring. Links between gene methylation and expression levels were assessed by correlating genomic findings with plasma markers of insulin resistance (fasting insulin and homeostatic model of insulin resistance). A total of 5,698 genes were differentially methylated between BMS and AMS siblings, exhibiting a preponderance of glucoregulatory, inflammatory, and vascular disease genes. Statistically significant correlations between gene methylation levels and gene expression and plasma markers of insulin resistance were consistent with metabolic improvements in AMS offspring, reflected in genes involved in diabetes-related cardiometabolic pathways. This unique clinical study demonstrates that effective treatment of a maternal phenotype is durably detectable in the methylome and transcriptome of subsequent offspring.
authors.affiliation: Institute of Nutrition and Functional Foods and Department of Food Science and Nutrition, Laval University, Quebec City, QC G1V 0A6, Canada.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Guénard
authors.forename: Yves
authors.initials: Y
authors.lastname: Deshaies
authors.forename: Katherine
authors.initials: K
authors.lastname: Cianflone
authors.forename: John G
authors.initials: JG
authors.lastname: Kral
authors.forename: Picard
authors.initials: P
authors.lastname: Marceau
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Vohl
mesh_terms: D000328:Adult; D002648:Child; D015331:Cohort Studies; D019175:DNA Methylation; D005260:Female; D015390:Gastric Bypass; D020869:Gene Expression Profiling; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D009765:Obesity / Q000150:complications / Q000235:genetics / Q000601:surgery*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics / Q000601:surgery*
chemical_list: D005947:Glucose
keywords: adiposity; developmental origins; epigenetics; glucose metabolism; intrauterine environment