Sleep Fragmentation During Late Gestation Induces Metabolic Perturbations and Epigenetic Changes in Adiponectin Gene Expression in Male Adult Offspring Mice

  1. David Gozal*
  1. Section of Pediatric Sleep Medicine, Department of Pediatrics, Comer Children’s Hospital, Biological Sciences Division, The University of Chicago, Chicago, IL
  1. *Corresponding Author: David Gozal, E-mail: dgozal{at}uchicago.edu

Abstract

Sleep fragmentation (SF) is a common condition among pregnant women, particularly during late gestation. Gestational perturbations promote the emergence of adiposity and metabolic disease risk in offspring, most likely via epigenetic modifications. Adiponectin (AdipoQ) expression inversely correlates with obesity and insulin-resistance. The effects of SF during late gestation on metabolic function and AdipoQ expression in visceral white adipose tissue (VWAT) of offspring mice are unknown. Male offspring mice were assessed at 24 weeks after dams were exposed to SF or control sleep (CS) during late gestation. Increased food intake, body weight, VWAT mass, and insulin resistance, with reductions in AdipoQ expression in VWAT emerged in SF offspring. Increased DNMT3a and b and global DNA methylation, and reduced HAT activity and TET1-2-and-3 expression were detected in VWAT of SF offspring. Reductions in 5-hydroxymethylcytosine and H3K4m3, and an increase in DNA 5-methylcytosine and H3K9m2 in the promoter and enhancer regions of AdipoQ emerged in adipocytes from VWAT, and correlated with AdipoQ expression. SF during late gestation induces epigenetic modifications in AdipoQ in male offspring VWAT adipocytes, along with a metabolic syndrome-like phenotype. Thus, altered gestational environments elicited by sleep fragmentation impose the emergence of adverse long-lasting metabolic consequences in the next generation.

  • Received February 8, 2014.
  • Accepted April 27, 2014.

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