Association of cholesterol oxidation and abnormalities in fatty acid metabolism in cystic fibrosis

Background: Disarrangement in fatty acids and oxidative stress are features of cystic fibrosis. Cholesterol is very sensitive to oxidative stress. Objectives: The objectives were to examine whether cholesterol oxidation products are altered in cystic fibrosis and whether they are associated with fatty acids and with characteristics of the disease state. Design: 7-Ketocholesterol and 7β-hydroxycholesterol (prototype molecules of free radical-mediated cholesterol oxidation) and the fatty acid profile were assessed by mass spectrometry in patients and in sex- and age-matched control subjects. Results: In a comparison with control subjects, mean (±SD) cholesterol oxidation was higher (7-ketocholesterol: 11.31 ± 5.1 compared with 8.33 ± 5.5 ng/mL, P = 0.03; 7β-hydroxycholesterol: 14.5 ± 6.8 compared with 9.7 ± 4.1 ng/mL, P = 0.004), total saturated fatty acids were higher (31.90 ± 1.93% compared with 30.31 ± 0.98%, P < 0.001), monounsaturated fatty acids were higher (29.14 ± 3.85% compared with 25.88 ± 2.94%, P = 0.004), ω-6 (n-6) polyunsaturated fatty acids were lower (34.84 ± 4.77 compared with 39.68 6± 2.98%, P < 0.0001), and ω-3 (n23) polyunsaturated fatty acids were comparable in patients with cystic fibrosis. Oxysterols were inversely associated with 24:0 and 18:2 ω-6 fatty acids but did not correlate with the increased oleic acid or with any of the ω-3 fatty acids. Conclusions: Cystic fibrosis is characterized by relevant cholesterol oxidation that is associated with an abnormal fatty acid profile. The interplay between oxysterols and fatty acids potentially provides insight into the biological mechanisms that underlie this complex disease.