|Andres, Aline -|
|Shankar, Kartik -|
Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: July 2, 2012
Publication Date: N/A
Technical Abstract: Currently in the United States more than 50% of women who become pregnant are either overweight or obese. Recent evidence suggests that both overweight and obese body composition status during pregnancy can lead to higher adiposity in infants and children. In light of the current incidence of overweight and obesity in pregnant women, one in two infants born in the United States will be exposed to an obesogenic intrauterine environment, raising its risk of developing obesity later in life. However, the mechanism by which this occurs is not yet understood. In a controlled animal model of maternal obesity, offspring born to obese dams are hyper-responsive to obesogenic high-fat diets, gaining greater body weight, adiposity, and metabolic sequelae. The Glowing study is an ongoing longitudinal observational study designed to test the hypothesis developed in the animal model whereby maternal obesity leads to metabolic programming of fetal metabolism such that energy sparing and higher fat deposition occurs in the offspring. The study is also designed to control for confounder factors such as gestational weigh gain, dietary intake, or physical activity differences in order to isolate the in utero maternal programming of offspring metabolism. Longitudinal preliminary analyses demonstrate that overweight and obese pregnant women (OW/OB, BMI 25-35) have altered insulin sensitivity compared to lean women (BMI 18.5-24.9) during the course of pregnancy. OW/OB women display hyperinsulinemia and hyperleptinemia compared to lean pregnant women, despite normal oral glucose tolerance test at gestation week 30. Analyses of the villous placental samples demonstrate that maternal obesity significantly affected expression of 406 genes (+/-1.5-fold, p<0.05), which were enriched for lipid metabolic process, leukocyte migration and cell adhesion. Moreover, phosphorylation of JNK1/2 and NF-'B was increased (2- and 2.2-fold, respectively) in placental lysates from obese women. Furthermore, genome-scale analysis of DNA methylation using reduced representation bisulfite sequencing, revealed that methylation of approx. 1,900 CpG sites was altered associated with maternal obesity. Our limited preliminary data from the first infants born in the study demonstrate higher levels of adiposity in infants born to OW/OB mothers compared to infants born to lean mothers (24.4% vs. 20.9%) at age 3 mo, validating our hypothesis that infants born to overweight or obese women have higher risk of obesity during infancy. In summary, our results demonstrate that maternal programming of offspring metabolism may be mediated by epigenetic regulation developed during the in utero period, which leads to an increase in adiposity post-natally.