Author
THAKALI, KESHARI - Arkansas Children'S Nutrition Research Center (ACNC) | |
SABEN, JESSICA - Arkansas Children'S Nutrition Research Center (ACNC) | |
FASKE, JENNIFER - Arkansas Children'S Nutrition Research Center (ACNC) | |
LINDSEY, FORREST - Arkansas Children'S Nutrition Research Center (ACNC) | |
GOMEZ-ACEVEDO, HORACIO - Arkansas Children'S Nutrition Research Center (ACNC) | |
LOWERY, CURTIS - University Arkansas For Medical Sciences (UAMS) | |
Badger, Thomas - Arkansas Children'S Nutrition Research Center (ACNC) | |
ANDRES, ALINE - Arkansas Children'S Nutrition Research Center (ACNC) | |
SHANKAR, KARTIK - Arkansas Children'S Nutrition Research Center (ACNC) |
Submitted to: Pediatric Research
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 2/6/2014 Publication Date: 8/20/2014 Citation: Thakali, K.M., Saben, J., Faske, J.B., Lindsey, F., Gomez-Acevedo, H., Lowery, C.L., Badger, T.M., Andres, A., Shankar, K. 2014. Maternal pregravid obesity changes gene expression profiles toward greater inflammation and reduced insulin sensitivity in umbilical cord. Pediatric Research. 76(2):202-210. Interpretive Summary: Increasing rates of adult and childhood obesity are occurring in both the United States and world-wide. While improper diet and lack of exercise contribute to the increasing incidence of obesity, there is also likely a genetic component to obesity that can be passed down from parents to children. The goal of our research is to determine if and how mom’s weight can affect their baby’s gene expression profile and their likelihood of becoming overweight or obese later on in life. We collected umbilical cords from lean and obese moms to compare their baby’s gene expression profile at birth. We observed that maternal obesity per se caused changes in umbilical cord gene expression favoring inflammation and insulin resistance, pathways that important in the development of obesity, suggesting that infants of overweight moms may be predisposed to become overweight later on in life. Technical Abstract: Background: Maternal obesity is associated with unfavorable outcomes, which may be reflected in the as yet undiscovered gene expression profiles of the umbilical cord (UC). Methods: UCs from 12 lean (pre-gravid BMI < 24.9) and 10 overweight/obese (OW/OB, pre-gravid BMI =25) women without gestational diabetes were collected for gene expression analysis using Human Primeview microarrays (Affymetrix). Metabolic parameters were assayed in mother’s plasma and cord blood. Results: Although offspring birth weight and adiposity (at 2-wk) did not differ between groups, expression of 232 transcripts was affected in UC from OW/OB compared to those of lean mothers. GSEA analysis revealed an up-regulation of genes related to metabolism, stimulus and defense response and inhibitory to insulin signaling in the OW/OB group. We confirmed that EGR1, periostin, and FOSB mRNA expression was induced in UCs from OW/OB moms, while endothelin receptor B, KFL10, PEG3 and EGLN3 expression was decreased. Messenger RNA expression of EGR1, FOSB, MEST and SOCS1 were positively correlated (p<0.05) with mother’s first trimester body fat mass (%). Conclusions: Our data suggest a positive association between maternal obesity and changes in UC gene expression profiles favoring inflammation and insulin resistance, potentially predisposing infants to develop metabolic dysfunction later on in life. |