Affordable Access

deepdyve-link
Publisher Website

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

Authors
  • 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, WY, USA.
  • 3 Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
  • 4 Department of Pathology, Indiana University School of Medicine, Indianapolis, IN, USA. , (India)
  • 5 Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN, USA. , (India)
  • 6 Department of Pediatrics, Division of Neonatology, University of Texas Health Science Center, San Antonio, TX, USA.
  • 7 Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, USA.
Type
Published Article
Journal
The Journal of Physiology
Publisher
Wiley (Blackwell Publishing)
Publication Date
Dec 01, 2018
Volume
596
Issue
23
Pages
5823–5837
Identifiers
DOI: 10.1113/JP275422
PMID: 29516496
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Maternal obesity (MO) and exposure to a high-fat, high-simple-carbohydrate diet during pregnancy predisposes offspring to obesity, metabolic and cardiovascular disorders in later life. Underlying molecular pathways and potential epigenetic factors that are dysregulated in MO were identified using unbiased transcriptomic methods. There was increased lipid accumulation and severe steatosis in the MO baboon fetal liver suggesting that these offspring are on an early trajectory of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. 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 the 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-fructose diet. Unbiased gene and microRNA (small RNA Seq) abundance analyses were performed on fetal baboon livers at 0.9 gestation and subjected to pathway analyses to identify fetal liver molecular responses to MO. Fetal baboon liver lipid and glycogen content were quantified by the 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 non-human primate fetal liver using unbiased transcriptome analysis to detect changes in hepatic gene expression levels and identify potential microRNA epigenetic regulators of metabolic disruption. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

Report this publication

Statistics

Seen <100 times