Lifestyle Intervention in Pregnant Women With Obesity Impacts Cord Blood DNA Methylation, Which Associates With Body Composition in the Offspring.
Josefine JönssonKristina M RenaultSonia García-CalzónAlexander PerfilyevAngela C EstampadorKirsten NørgaardMads Vendelbo LindAllan Arthur VaagLine HjortKim F MichaelsenEmma Malchau CarlsenPaul W FranksCharlotte LingPublished in: Diabetes (2021)
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 Treatment of Obese Pregnant women (TOP)-study, which includes pregnant women with obesity randomized to lifestyle interventions comprised of physical activity with or without dietary advice versus control subjects (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 control subjects (false discovery rate [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 with control subjects. Methylation at 17 sites, annotated to, for example, 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.
Keyphrases
- cord blood
- dna methylation
- weight loss
- metabolic syndrome
- genome wide
- high fat diet
- physical activity
- insulin resistance
- body composition
- pregnant women
- adipose tissue
- bariatric surgery
- randomized controlled trial
- gene expression
- type diabetes
- cardiovascular disease
- bone mineral density
- high fat diet induced
- weight gain
- resistance training
- copy number
- healthcare
- body mass index
- fatty acid
- depressive symptoms
- obese patients
- palliative care
- smoking cessation
- sleep quality
- postmenopausal women
- clinical trial
- mesenchymal stem cells
- cell therapy
- pain management
- health insurance
- open label
- genome wide identification
- birth weight
- preterm infants
- small molecule
- single cell