title: Inflammation mediates the association between visceral adiposity and obstructive sleep apnea in adolescents.
abstract: Only a handful of studies, primarily in clinical samples, have reported an association between obesity, inflammation, and obstructive sleep apnea (OSA) in children and adolescents. No studies, however, have examined the pathogenetic link between visceral adiposity, systemic inflammation, and incident OSA in a large general population sample using objective measures of sleep and body fat. Adolescents (n = 392; mean age 17.0 ± 2.2 yr, 54.0% male) from the Penn State Child Cohort (PSCC) underwent 9-h overnight polysomnography; a DXA scan to assess body fat distribution; and a single fasting blood draw for the assessment of plasma interleukin-6 (IL-6), IL-6 soluble receptor (IL-6 sR), tumor necrosis factor alpha (TNFα), tumor necrosis factor receptor 1A (TNFR1), C-reactive protein (CRP), leptin, and adiponectin levels via ELISA. Visceral fat area was significantly elevated in moderate OSA (AHI ≥ 5), especially in boys. IL-6, CRP, and leptin were highest in adolescents with moderate OSA, even after adjusting for BMI percentile. Mediation analysis revealed that 42% of the association between visceral fat and OSA in adolescents was mediated by IL-6 (p = 0.03), while 82% of the association was mediated by CRP (p = 0.01). These data are consistent with the model of a feed-forward, vicious cycle, in which the release of proinflammatory cytokines by visceral adipocytes largely explains the association between central obesity and OSA; in turn, inflammation is also elevated in OSA independent of BMI. These findings, in a large, representative, non-clinical sample of young people, add to our understanding of the developmental pathogenesis of sleep apnea.
authors.affiliation: Sleep Research and Treatment Center, Department of Psychiatry, Pennsylvania State University College of Medicine, Hershey, Pennsylvania; and.
authors.forename: Jordan
authors.initials: J
authors.lastname: Gaines
authors.affiliation: Sleep Research and Treatment Center, Department of Psychiatry, Pennsylvania State University College of Medicine, Hershey, Pennsylvania; and avgontzas@psu.edu.
authors.forename: Alexandros N
authors.initials: AN
authors.lastname: Vgontzas
authors.affiliation: Sleep Research and Treatment Center, Department of Psychiatry, Pennsylvania State University College of Medicine, Hershey, Pennsylvania; and.
authors.forename: Julio
authors.initials: J
authors.lastname: Fernandez-Mendoza
authors.affiliation: Sleep Research and Treatment Center, Department of Psychiatry, Pennsylvania State University College of Medicine, Hershey, Pennsylvania; and.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Calhoun
authors.affiliation: Department of Public Health Sciences, Pennsylvania State University College of Medicine, Hershey, Pennsylvania.
authors.forename: Fan
authors.initials: F
authors.lastname: He
authors.affiliation: Department of Public Health Sciences, Pennsylvania State University College of Medicine, Hershey, Pennsylvania.
authors.forename: Duanping
authors.initials: D
authors.lastname: Liao
authors.affiliation: Department of Public Health Sciences, Pennsylvania State University College of Medicine, Hershey, Pennsylvania.
authors.forename: Marjorie D
authors.initials: MD
authors.lastname: Sawyer
authors.affiliation: Sleep Research and Treatment Center, Department of Psychiatry, Pennsylvania State University College of Medicine, Hershey, Pennsylvania; and.
authors.forename: Edward O
authors.initials: EO
authors.lastname: Bixler
mesh_terms: D015502:Absorptiometry, Photon; D054392:Adipokines / Q000276:immunology*; D052242:Adiponectin / Q000276:immunology; D000293:Adolescent; D050218:Body Fat Distribution; D002097:C-Reactive Protein / Q000276:immunology*; D015897:Comorbidity; D016207:Cytokines / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007249:Inflammation; D015850:Interleukin-6 / Q000276:immunology; D020738:Leptin / Q000276:immunology; D008297:Male; D056128:Obesity, Abdominal / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000276:immunology*; D017286:Polysomnography; D018121:Receptors, Cytokine / Q000276:immunology*; D019947:Receptors, Interleukin-6 / Q000276:immunology; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000276:immunology; D012737:Sex Factors; D020181:Sleep Apnea, Obstructive / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D055815:Young Adult
chemical_list: C499918:ADIPOQ protein, human; D054392:Adipokines; D052242:Adiponectin; D016207:Cytokines; C508600:IL6 protein, human; C508603:IL6R protein, human; D015850:Interleukin-6; D020738:Leptin; D018121:Receptors, Cytokine; D019947:Receptors, Interleukin-6; D047888:Receptors, Tumor Necrosis Factor, Type I; C439524:TNF protein, human; C506235:TNFRSF1A protein, human; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein
keywords: adolescents; inflammation; obesity; obstructive sleep apnea; sleep-disordered breathing