title: Chronic intermittent hypoxia is a major trigger for non-alcoholic fatty liver disease in morbid obese.
abstract: OBJECTIVE
  Morbid obesity is frequently associated with low grade systemic inflammation, increased macrophage accumulation in adipose tissue (AT), obstructive sleep apnea (OSA), and nonalcoholic fatty liver disease (NAFLD). It has been suggested that chronic intermittent hypoxia (CIH) resulting from OSA could be an independent factor for early stage of NAFLD in addition to other well-recognized factors (dyslipidemia or insulin resistance). Moreover, macrophage accumulation in AT is associated with local hypoxia in fat tissue. We hypothesized that the association between CIH and morbid obesity could exert additional specific deleterious effects both in the liver and adipose tissues.
  
  
  METHODS
  One hundred and one morbidly obese subjects were prospectively recruited and underwent bariatric surgery during which a liver needle biopsy as well as surgical subcutaneous and omental AT biopsies were obtained. Oxygen desaturation index (ODI) quantified the severity of nocturnal CIH.
  
  
  RESULTS
  Histopathologic analysis of liver biopsies demonstrated that NAFLD lesions (ballooning of hepatocytes, lobular inflammation), NAFLD activity score (NAS), and fibrosis were significantly more severe in patients with the highest ODI tertile (p values ≤0.001 for all hepatic lesions). In multivariate analysis, after adjustment for age, obesity, and insulin resistance status, CIH remained independently associated with hepatic fibrosis, fibroinflammation, and NAS. By contrast, no association was found between CIH, macrophage accumulation, and adipocytes size in both subcutaneous and omental adipose tissue.
  
  
  CONCLUSIONS
  In morbidly obese patients, CIH was strongly associated with more severe liver injuries but did not worsen obesity induced macrophage accumulation in adipose tissue depots.
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Endocrinology and Nutrition Department, and Center of Human Nutrition (CRNH), Pitié-Salpétrière Hospital, Paris 75613, France.
authors.forename: Judith
authors.initials: J
authors.lastname: Aron-Wisnewsky
authors.forename: Caroline
authors.initials: C
authors.lastname: Minville
authors.forename: Joan
authors.initials: J
authors.lastname: Tordjman
authors.forename: Patrick
authors.initials: P
authors.lastname: Lévy
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Bouillot
authors.forename: Arnaud
authors.initials: A
authors.lastname: Basdevant
authors.forename: Pierre
authors.initials: P
authors.lastname: Bedossa
authors.forename: Karine
authors.initials: K
authors.lastname: Clément
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Pépin
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D050110:Bariatric Surgery; D002908:Chronic Disease; D015331:Cohort Studies; D005234:Fatty Liver / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D007333:Insulin Resistance; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D009767:Obesity, Morbid / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D011446:Prospective Studies; D012307:Risk Factors; D020181:Sleep Apnea, Obstructive / Q000150:complications / Q000378:metabolism