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This Article Full Text Full Text (PDF) All Versions of this Article: 90/3/477    most recent ajcn.2009.27757v1 Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Iuliano, L. Articles by Quattrucci, S. PubMed PubMed Citation Articles by Iuliano, L. Articles by Quattrucci, S. Agricola Articles by Iuliano, L. Articles by Quattrucci, S.

Association of cholesterol oxidation and abnormalities in fatty acid metabolism in cystic fibrosis^1,2,3

¹ From the Department of Experimental Medicine, Unit of Vascular Medicine & Mass Spectrometry Laboratory (LI, RM, and GS); the Department of Pediatrics, Cystic Fibrosis Center, Sapienza University of Rome, Rome, Italy (SZ and SQ); the Department of Internal Medicine, Unit of Biochemistry & Nutrition, University of Perugia, Perugia, Italy (FG); and the E Wolfson Medical Center and Tel Aviv University, Unit of Epidemiology and Statistics, Holon, Israel (MB).

² Supported by grants from the Ministero dell' Università, Ricerca Scientifica e Tecnologica (PRIN 2007L7BHK8), Sapienza University of Rome, and the Italian Cystic Fibrosis Foundation.

³ Address correspondence to L Iuliano, Sapienza University of Rome, Department of Experimental Medicine, Unit of Vascular Medicine & Mass Spectrometry Laboratory, Corso della Republica 79, 04100 Latina, Italy. E-mail: luigi.iuliano{at}uniroma1.it.

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), -6 (n–6) polyunsaturated fatty acids were lower (34.84 ± 4.77 compared with 39.68 ± 2.98%, P < 0.0001), and -3 (n–3) polyunsaturated fatty acids were comparable in patients with cystic fibrosis. Oxysterols were inversely associated with 24:0 and 18:2 -6 fatty acids but did not correlate with the increased oleic acid or with any of the -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.