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

Rahul Yadav, Michael France, Reza Aghamohammadzadeh, Yifen Liu, Salam Hama, See Kwok, Jonathan Schofield, Peter Turkington, Akheel A. Syed, Rayaz Malik, Philip Pemberton, Adam Greenstein, Paul Durrington, Basil Ammori, Martin Gibson, Maria Jeziorska, Handrean Soran

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Abstract

Design and Patients: Morbidly obese patients (n = 41) were divided into those whose apneahypoapnea 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=.005andP<.05, respectively). SerumTNFα andICAM-1 levelsandTNFα 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.

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. Copyright

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.

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.

Original languageEnglish
Pages (from-to)3390-3398
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume99
Issue number9
DOIs
Publication statusPublished - 1 Sep 2014
Externally publishedYes

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ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Yadav, R., France, M., Aghamohammadzadeh, R., Liu, Y., Hama, S., Kwok, S., Schofield, J., Turkington, P., Syed, A. A., Malik, R., Pemberton, P., Greenstein, A., Durrington, P., Ammori, B., Gibson, M., Jeziorska, M., & Soran, H. (2014). Impairment of high-density lipoprotein resistance to lipid peroxidation and adipose tissue inflammation in obesity complicated by obstructive sleep apnea. Journal of Clinical Endocrinology and Metabolism, 99(9), 3390-3398. https://doi.org/10.1210/jc.2013-3939