Abstract
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.
Document Type
Article
Publication Date
10-2017
Digital Object Identifier (DOI)
https://doi.org/10.1017/S2040174417000290
Funding Information
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).
Related Content
Refer to Web version on PubMed Central for supplementary material.
Repository Citation
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.
https://uknowledge.uky.edu/pharmacol_facpub/80
Supplemental Table 1. Gene list for NanoString CodeSet.
Included in
Biostatistics Commons, Congenital, Hereditary, and Neonatal Diseases and Abnormalities Commons, Genetics and Genomics Commons
Notes/Citation Information
Published in Journal of Developmental Origins of Health and Disease, v. 8, issue 5, p. 575-583.
This article has been published in a revised form in Journal of Developmental Origins of Health and Disease https://doi.org/10.1017/S2040174417000290. This version is published under a Creative Commons CC-BY-NC-ND. No commercial re-distribution or re-use allowed. Derivative works cannot be distributed. © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2017.
The document available for download is the author's post-peer-review final draft of the article.