title: Obesity accentuates circadian variability in breathing during sleep in mice but does not predispose to apnea.
abstract: Obesity is a primary risk factor for the development of obstructive sleep apnea in humans, but the impact of obesity on central sleep apnea is less clear. Given the comorbidities associated with obesity in humans, we developed techniques for long-term recording of diaphragmatic EMG activity and polysomnography in obese mice to assess breathing patterns during sleep and to determine the effect of obesity on apnea generation. We hypothesized that genetically obese ob/ob mice would exhibit less variability in breathing across the 24-h circadian cycle, be more prone to central apneas, and be more likely to exhibit patterns of increased diaphragm muscle activity consistent with obstructive apneas compared with lean mice. Unexpectedly, we found that obese mice exhibited a greater circadian impact on respiratory rate and diaphragmatic burst amplitude than lean mice, particularly during rapid eye movement (REM) sleep. Central apneas were more common in REM sleep (42 ± 17 h(-1)) than non-REM (NREM) sleep (14 ± 5 h(-1)) in obese mice (P < 0.05), but rates were not different between lean and obese mice in either sleep state. Even after experimentally enhancing central apnea generation by acute withdrawal of hypoxic chemoreceptor activation during sleep, central apnea rates remained comparable between lean and obese mice. Last, we were unable to detect patterns of diaphragmatic burst activity suggestive of obstructive apnea events in obese mice. In summary, obesity does not predispose mice to increased occurrence of central or obstructive apneas during sleep, but does lead to a more pronounced circadian variability in respiration.
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. davisem2@upmc.edu
authors.forename: Eric M
authors.initials: EM
authors.lastname: Davis
authors.forename: Landon W
authors.initials: LW
authors.lastname: Locke
authors.forename: Angela L
authors.initials: AL
authors.lastname: McDowell
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Strollo
authors.forename: Christopher P
authors.initials: CP
authors.lastname: O'Donnell
mesh_terms: D000818:Animals; D057906:Circadian Clocks / Q000502:physiology*; D003964:Diaphragm / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000503:physiopathology*; D017286:Polysomnography / Q000379:methods; D012119:Respiration; D012890:Sleep / Q000502:physiology*; D020182:Sleep Apnea, Central / Q000503:physiopathology*; D020181:Sleep Apnea, Obstructive / Q000503:physiopathology*; D012895:Sleep, REM / Q000502:physiology
keywords: central sleep apnea; circadian variability; control of breathing; obesity; obstructive sleep apnea