Elevated birth weight is linked to glucose intolerance and obesity health-related complications later in life. No studies have examined if infant birth weight is associated with gene expression markers of obesity and inflammation in a tissue that comes directly from the infant following birth. We evaluated the association between birth weight and gene expression on fetal programming of obesity. Foreskin samples were collected following circumcision, and gene expression analyzed comparing the 15% greatest birth weight infants (n = 7) v. the remainder of the cohort (n = 40). Multivariate linear regression models were fit to relate expression levels on differentially expressed genes to birth weight group with adjustment for variables selected from a list of maternal and infant characteristics. Glucose transporter type 4 (GLUT4), insulin receptor substrate 2 (IRS2), leptin receptor (LEPR), lipoprotein lipase (LPL), low-density lipoprotein receptor-related protein 1 (LRP1), matrix metalloproteinase 2 (MMP2), plasminogen activator inhibitor-1 (PAI-1) and transcription factor 7-like 2 (TCF7L2) were significantly upregulated and histone deacetylase 1 (HDAC1) and thioredoxin (TXN) downregulated in the larger birth weight neonates v. controls. Multivariate modeling revealed that the estimated adjusted birth weight group difference exceeded one standard deviation of the expression level for eight of the 10 genes. Between 25 and 50% of variation in expression level was explained by multivariate modeling for eight of the 10 genes. Gene expression related to glycemic control, appetite/energy balance, obesity and inflammation were altered in tissue from babies with elevated birth weight, and these genes may provide important information regarding fetal programming in macrosomic babies.
Digital Object Identifier (DOI)
Funding for the study was generously provided by the Graduate Center for Nutritional Sciences at the University of Kentucky. A.J.S and S.S. were supported by the National Institutes of Health (NIH) (P20GM103436–15). Additionally, A.J.S. was supported by NIH CTSA Award (UL1TR000117). R.J.C. was supported, in part, by the NIH (P20GM103527–08). L.J.R. was supported by an American Heart Association Post-Doctoral Fellowship (15POST25110002). C.S.R. was supported by NIH training grants (T32DK07778 and T32HD060556).
Refer to Web version on PubMed Central for supplementary material.
Reynolds, Leryn J.; Pollack, Rebecca I.; Charnigo, Richard J.; Rashid, Cetewayo S.; Stromberg, Arnold J.; Shen, Shu; O'Brien, John; and Pearson, Kevin J., "Increased Birth Weight is Associated with Altered Gene Expression in Neonatal Foreskin" (2017). Pharmacology and Nutritional Sciences Faculty Publications. 80.