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Primate fetal hepatic responses to maternal obesity: epigenetic signalling pathways and lipid accumulation.

  • Puppala, Sobha1
  • Li, Cun2
  • Glenn, Jeremy P3
  • Saxena, Romil4
  • Gawrieh, Samer5
  • Quinn, Amy6
  • Palarczyk, Jennifer6
  • Dick, Edward J Jr7
  • Nathanielsz, Peter W2, 3
  • Cox, Laura A1, 7
  • 1 Department of Internal Medicine, Section of Molecular Medicine, Wake Forest Baptist, Medical Center, Winston-Salem, NC, USA.
  • 2 Department of Animal Science, University of Wyoming, Laramie, Wyoming, USA.
  • 3 Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas.
  • 4 Department of Pathology Indiana University School of Medicine Indianapolis, Indianapolis, IN. , (India)
  • 5 Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN. , (India)
  • 6 Department of Pediatrics, Division of Neonatology, University of Texas Health Science Center, San Antonio, Texas.
  • 7 Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, Texas.
Published Article
The Journal of Physiology
Wiley (Blackwell Publishing)
Publication Date
Mar 07, 2018
DOI: 10.1113/JP275422
PMID: 29516496


Maternal obesity (MO) increases offspring cardiometabolic disease risk. Altered fetal liver development in response to the challenge of MO has metabolic consequences underlying adverse offspring life-course health outcomes. Little is known about molecular pathways and potential epigenetic changes regulating primate fetal liver responses to MO. We hypothesized that MO would induce fetal baboon liver epigenetic changes resulting in dysregulation of key metabolic pathways that impact lipid metabolism. MO was induced prior to pregnancy by a high fat, high sucrose diet. Unbiased gene and microRNA (miRNA; small RNA Seq) abundance analyses were performed on fetal baboon livers at 0.9 gestation (G) and subjected to pathway analyses to identify fetal liver molecular responses to MO. Fetal baboon liver lipid and glycogen content were quantified by Computer Assisted Stereology Toolbox. In response to MO, fetal livers revealed dysregulation of TCA cycle, proteasome, oxidative phosphorylation, glycolysis and Wnt/β-catenin signalling pathways together with marked lipid accumulation supporting our hypothesis that multiple pathway dysregulation detrimentally impacts lipid management. This is the first study of MO programming of the nonhuman primate fetal liver using unbiased transcriptome analysis to detect changes in hepatic gene expression levels and identify potential miRNA epigenetic regulators of metabolic disruption. This article is protected by copyright. All rights reserved.

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