Association of Cystic Fibrosis with Abnormalities in Fatty Acid Metabolism

• Published in: The New England journal of medicine Vol. 350; no. 6; pp. 560 - 569
• Main Authors: Freedman, Steven D, Blanco, Paola G, Zaman, Munir M, Shea, Julie C, Ollero, Mario, Hopper, Isabel K, Weed, Deborah A, Gelrud, Andres, Regan, Meredith M, Laposata, Michael, Alvarez, Juan G, O'Sullivan, Brian P
• Format: Journal Article
• Language: English
• Published: Boston, MA Massachusetts Medical Society 05.02.2004
• Subjects: Arachidonic Acid - metabolism; Asthma; Asthma - metabolism; Biological and medical sciences; Biopsy; Case-Control Studies; Cystic fibrosis; Cystic Fibrosis - metabolism; Cystic Fibrosis Transmembrane Conductance Regulator - genetics; Cystic Fibrosis Transmembrane Conductance Regulator - metabolism; Docosahexaenoic Acids - metabolism; Errors of metabolism; Family medical history; Fatty acids; Fatty Acids - blood; Fatty Acids - metabolism; Heterozygote; Humans; Inflammatory Bowel Diseases - metabolism; Medical sciences; Metabolic diseases; Miscellaneous hereditary metabolic disorders; Mutation; Nose - metabolism; Rectum - metabolism; Reference Values; Respiratory Tract Infections - metabolism; Human; Pathophysiology; Respiratory disease; Metabolic diseases; Lipids; Cystic fibrosis; Metabolism; Fatty acids; Genetic disease; Concomitant disease; Metabolic disorder; Association; Digestive diseases; Pancreatic disease
• ISSN: 0028-4793; 1533-4406; 1533-4406
• DOI: 10.1056/NEJMoa021218

Patients with cystic fibrosis have altered levels of plasma fatty acids, but whether these abnormalities reflect inflammation or a primary defect in fatty acid metabolism is not known. In this study, investigators profiled fatty acids in subjects with cystic fibrosis, healthy controls, subjects with inflammatory bowel disease, and subjects with asthma. The ratio of arachidonic to docosahexaenoic acid was increased in subjects with cystic fibrosis, as compared with healthy controls. Genetic abnormalities of the transmembrane conductance regulator and abnormal profiles of fatty acids. The mechanisms by which mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein lead to the expression of cystic fibrosis are unclear. Explanations must take into account the increased viscosity of ductal fluids as well as the excessive host inflammatory response. 1 – 6 Alterations in the metabolism of fatty acids may have an important role. 7 A deficiency of essential fatty acids has been described in patients with cystic fibrosis 8 that is characterized by a decrease in the plasma levels of linoleic acid (18:2n–6) and docosahexaenoic acid (22:6n–3) with a compensatory increase in the levels of eicosatrienoic acid . . .