title: Sleep fragmentation promotes NADPH oxidase 2-mediated adipose tissue inflammation leading to insulin resistance in mice.
abstract: BACKGROUND
  Short sleep has been implicated in higher risk of obesity in humans, and is associated with insulin resistance. However, the effects of fragmented sleep (SF) rather than curtailed sleep on glucose homeostasis are unknown.
  
  
  METHODS
  Wild-type and NADPH oxidase 2 (Nox2) null male mice were subjected to SF or sleep control conditions for 3 days to 3 weeks. Systemic and visceral adipose tissue (VAT) insulin sensitivity tests, glucose tolerance test, fluorescence-activated cell sorting and immunohistochemistry for macrophages and its sub-types (M1 and M2), and Nox expression and activity were examined.
  
  
  RESULTS
  Here we show that SF in the absence of sleep curtailment induces time-dependent insulin resistance, in vivo and also in vitro in VAT. Oxidative stress pathways were upregulated by SF in VAT, and were accompanied by M1 macrophage polarization. SF-induced oxidative stress, inflammation and insulin resistance in VAT were completely abrogated in genetically altered mice lacking Nox2 activity.
  
  
  CONCLUSIONS
  These studies imply that SF, a frequent occurrence in many disorders and more specifically in sleep apnea, is a potent inducer of insulin resistance via activation of oxidative stress and inflammatory pathways, thereby opening the way for therapeutic strategies.
authors.affiliation: Section of Pediatric Sleep Medicine, Department of Pediatrics, The University of Chicago, Chicago, IL, USA.
authors.forename: S X L
authors.initials: SX
authors.lastname: Zhang
authors.affiliation: Section of Pediatric Sleep Medicine, Department of Pediatrics, The University of Chicago, Chicago, IL, USA.
authors.forename: A
authors.initials: A
authors.lastname: Khalyfa
authors.affiliation: Section of Pediatric Sleep Medicine, Department of Pediatrics, The University of Chicago, Chicago, IL, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Section of Pediatric Sleep Medicine, Department of Pediatrics, The University of Chicago, Chicago, IL, USA.
authors.forename: A
authors.initials: A
authors.lastname: Carreras
authors.affiliation: Section of Pediatric Sleep Medicine, Department of Pediatrics, The University of Chicago, Chicago, IL, USA.
authors.forename: F
authors.initials: F
authors.lastname: Hakim
authors.affiliation: Section of Endocrinology, Department of Medicine, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL, USA.
authors.forename: B A
authors.initials: BA
authors.lastname: Neel
authors.affiliation: Section of Endocrinology, Department of Medicine, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Brady
authors.affiliation: Section of Pediatric Sleep Medicine, Department of Pediatrics, The University of Chicago, Chicago, IL, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Qiao
authors.affiliation: Section of Pediatric Sleep Medicine, Department of Pediatrics, The University of Chicago, Chicago, IL, USA.
authors.forename: C
authors.initials: C
authors.lastname: Hirotsu
authors.affiliation: Section of Pediatric Sleep Medicine, Department of Pediatrics, The University of Chicago, Chicago, IL, USA.
authors.forename: D
authors.initials: D
authors.lastname: Gozal
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D005951:Glucose Tolerance Test; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000209:etiology / Q000378:metabolism*; D007333:Insulin Resistance; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000378:metabolism*; D018384:Oxidative Stress; D015398:Signal Transduction; D012892:Sleep Deprivation / Q000150:complications / Q000378:metabolism*
chemical_list: D019255:NADPH Oxidases
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