TY - JOUR

T1 - Lifestyle intervention in pregnant women with obesity impacts cord blood DNA methylation which associates with body composition in the offspring

AU - Jönsson, Josefine

AU - Renault, Kristina Martha

AU - García-Calzón, Sonia

AU - Perfilyev, Alexander

AU - Estampador, Angela C

AU - Nørgaard, Kirsten

AU - Lind, Mads Vendelbo

AU - Vaag, Allan

AU - Hjort, Line

AU - Michaelsen, Kim F.

AU - Carlsen, Emma Malchau

AU - Franks, Paul W

AU - Ling, Charlotte

N1 - © 2021 by the American Diabetes Association.

PY - 2021

Y1 - 2021

N2 - Maternal obesity may lead to epigenetic alterations in the offspring and might thereby contribute to disease later in life. We investigated whether a lifestyle intervention in pregnant women with obesity is associated with epigenetic variation in cord blood and body composition in the offspring. Genome-wide DNA methylation was analyzed in cord blood from 208 offspring from the TOP-study, which includes pregnant women with obesity randomized to lifestyle interventions comprised of physical activity with or without dietary advice versus controls (standard of care). DNA methylation was altered at 379 sites, annotated to 370 genes, in cord blood from offspring of mothers following a lifestyle intervention versus controls (FDR<5%) when using the Houseman reference-free method to correct for cell composition and three of these sites were significant based on Bonferroni correction. These 370 genes are overrepresented in gene ontology terms including response to fatty acids and adipose tissue development. Offspring of mothers included in a lifestyle intervention were born with more lean mass compared to controls. Methylation at 17 sites, annotated to e.g. DISC1, GBX2, HERC2 and HUWE1, partially mediates the effect of the lifestyle intervention on lean mass in the offspring (FDR<5%). Moreover, 22 methylation sites were associated with offspring BMI z-scores during the first 3 years of life (p<0.05). Overall, lifestyle interventions in pregnant women with obesity are associated with epigenetic changes in offspring, potentially influencing the offspring's lean mass and early growth.

AB - Maternal obesity may lead to epigenetic alterations in the offspring and might thereby contribute to disease later in life. We investigated whether a lifestyle intervention in pregnant women with obesity is associated with epigenetic variation in cord blood and body composition in the offspring. Genome-wide DNA methylation was analyzed in cord blood from 208 offspring from the TOP-study, which includes pregnant women with obesity randomized to lifestyle interventions comprised of physical activity with or without dietary advice versus controls (standard of care). DNA methylation was altered at 379 sites, annotated to 370 genes, in cord blood from offspring of mothers following a lifestyle intervention versus controls (FDR<5%) when using the Houseman reference-free method to correct for cell composition and three of these sites were significant based on Bonferroni correction. These 370 genes are overrepresented in gene ontology terms including response to fatty acids and adipose tissue development. Offspring of mothers included in a lifestyle intervention were born with more lean mass compared to controls. Methylation at 17 sites, annotated to e.g. DISC1, GBX2, HERC2 and HUWE1, partially mediates the effect of the lifestyle intervention on lean mass in the offspring (FDR<5%). Moreover, 22 methylation sites were associated with offspring BMI z-scores during the first 3 years of life (p<0.05). Overall, lifestyle interventions in pregnant women with obesity are associated with epigenetic changes in offspring, potentially influencing the offspring's lean mass and early growth.

U2 - 10.2337/db20-0487

DO - 10.2337/db20-0487

M3 - Journal article

C2 - 33431374

VL - 70

SP - 854

EP - 866

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 4

ER -