Impairment of high-density lipoprotein resistance to lipid peroxidation and adipose tissue inflammation in obesity complicated by obstructive sleep apnea

J Clin Endocrinol Metab. 2014 Sep;99(9):3390-8. doi: 10.1210/jc.2013-3939. Epub 2014 May 13.


Context: Obstructive sleep apnea (OSA) complicates morbid obesity and is associated with increased cardiovascular disease incidence. An increase in the circulating markers of chronic inflammation and dysfunctional high-density lipoprotein (HDL) occur in severe obesity.

Objective: The objective of the study was to establish whether the effects of obesity on inflammation and HDL dysfunction are more marked when complicated by OSA.

Design and patients: Morbidly obese patients (n = 41) were divided into those whose apnea-hypoapnea index (AHI) was more or less than the median value and on the presence of OSA [OSA and no OSA (nOSA) groups]. We studied the antioxidant function of HDL and measured serum paraoxonase 1 (PON1) activity, TNFα, and intercellular adhesion molecule 1 (ICAM-1) levels in these patients. In a subset of 19 patients, we immunostained gluteal sc adipose tissue (SAT) for TNFα, macrophages, and measured adipocyte size.

Results: HDL lipid peroxide levels were higher and serum PON1 activity was lower in the high AHI group vs the low AHI group (P < .05 and P < .0001, respectively) and in the OSA group vs the nOSA group (P = .005 and P < .05, respectively). Serum TNFα and ICAM-1 levels and TNFα immunostaining in SAT increased with the severity of OSA. Serum PON1 activity was inversely correlated with AHI (r = -0.41, P < .03) in the OSA group. TNFα expression in SAT directly correlated with AHI (r = 0.53, P < .03) in the subset of 19 patients from whom a biopsy was obtained.

Conclusion: Increased serum TNFα, ICAM-1, and TNFα expression in SAT provide a mechanistic basis for enhanced inflammation in patients with OSA. Decreased serum PON1 activity, impaired HDL antioxidant function, and increased adipose tissue inflammation in these patients could be a mechanism for HDL and endothelial dysfunction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / immunology
  • Adipose Tissue / metabolism*
  • Adult
  • Antioxidants / metabolism
  • Aryldialkylphosphatase / immunology
  • Aryldialkylphosphatase / metabolism
  • Buttocks
  • Female
  • Humans
  • Intercellular Adhesion Molecule-1 / immunology
  • Intercellular Adhesion Molecule-1 / metabolism
  • Lipid Metabolism / immunology
  • Lipid Peroxidation / physiology*
  • Lipoproteins, HDL / metabolism*
  • Male
  • Middle Aged
  • Obesity, Morbid / complications
  • Obesity, Morbid / immunology
  • Obesity, Morbid / metabolism*
  • Panniculitis / complications
  • Panniculitis / immunology
  • Panniculitis / metabolism*
  • Sleep Apnea, Obstructive / complications
  • Sleep Apnea, Obstructive / immunology
  • Sleep Apnea, Obstructive / metabolism*
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism
  • Vasculitis / complications
  • Vasculitis / immunology
  • Vasculitis / metabolism


  • Antioxidants
  • Lipoproteins, HDL
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1
  • Aryldialkylphosphatase
  • PON1 protein, human