ESPE Abstracts

Introduction: The CCDC3 gene encodes for a protein expressed in endothelial cells and adipose tissue. Insulin increases its expression and, in turn, CCDC3 positively regulates adipogenesis and lipid accumulation. CCDC3 expression is increased in visceral adipose tissue from subjects with obesity. Gestational obesity can modify the metabolic programming in the offspring through epigenetic mechanisms. However, it is unknown whether the methylation of the CCDC3 gene can explain the relationship between gestational obesity and childhood obesity.

Objective: To study the methylation of CCDC3 in the placenta and peripheral blood in school-age children, analyze the associations with obesity and insulin resistance parameters in children and study whether maternal obesity can modulate these associations.

Methods: The study population consisted of a prenatal cohort of pregnant women and their newborns (n=125) who were followed from birth to school age (mean age 6.1 ± 0.9 years). Children were classified into two subgroups according to their mother's gestational weight gain [normal pregnancy weight gain (n=72) and gestational obesity (n=53)]. The methylation of two cytosine guanine dinucleotide sites (CpGs) of the CCDC3 gene was studied using pyrosequencing in placental and peripheral blood samples in the children. The correlation of CCDC3 methylation with parameters of obesity [weight, height, BMI, fat mass, visceral fat and serum lipids] and insulin resistance [glucose, insulin and HOMA-IR] was assessed.

Results: The methylation of CCDC3 (mean methylation of the studied CpGs) in peripheral blood was positively associated with obesity and insulin resistance parameters in school-age children: fat mass (r= 0.200; P=0.013), visceral fat (r= 0.193; P=0.034), glucose (r= 0.285; P=0.010) and HOMA-IR (r= 0.192; P=0.032). These associations were more evident in children born to mothers with gestational obesity (r between 0.277 and 0.300), in whom a negative correlation with HDL cholesterol was also evident (r= -0.344; P=0.014). In addition, in this group, peripheral blood methylation of CCDC3 was correlated with placental methylation of CCDC3 (r= 0.348; P=0.022). All these associations were independent from children’s sex, age and BMI in multivariate analyses (β between -0.325 and 0.340).

Conclusions: Our results show that CCDC3 methylation is associated with obesity and insulin resistance parameters in school-age children and is modulated by maternal gestational obesity. In addition, methylation of CCDC3 persists over time from birth (placenta) to school age (peripheral blood). We suggest that epigenetic alterations in CCDC3 can condition the development of childhood obesity and that maternal gestational obesity can aggravate such metabolic programming.