title: Increased elongase 6 and Δ9-desaturase activity are associated with n-7 and n-9 fatty acid changes in cystic fibrosis.
abstract: Patients with cystic fibrosis, caused by mutations in CFTR, exhibit specific and consistent alterations in the levels of particular unsaturated fatty acids compared with healthy controls. Evidence suggests that these changes may play a role in the pathogenesis of this disease. Among these abnormalities are increases in the levels of n-7 and n-9 fatty acids, particularly palmitoleate (16:1n-7), oleate (18:1n-9), and eicosatrienoate or mead acid (20:3n-9). The underlying mechanisms of these particular changes are unknown, but similar changes in the n-3 and n-6 fatty acid families have been correlated with increased expression of fatty acid metabolic enzymes. This study demonstrated that cystic fibrosis cells in culture exhibit increased metabolism along the metabolic pathways leading to 16:1n-7, 18:1n-9, and 20:3n-9 compared with wild-type cells. Furthermore, these changes are accompanied by increased expression of the enzymes that produce these fatty acids, namely Δ5, Δ6, and Δ9 desaturases and elongases 5 and 6. Taken together, these findings suggest that fatty acid abnormalities of the n-7 and n-9 series in cystic fibrosis are as a result, at least in part, of increased expression and activity of these metabolic enzymes in CFTR-mutated cells.
authors.affiliation: Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Kelly F
authors.initials: KF
authors.lastname: Thomsen
authors.forename: Michael
authors.initials: M
authors.lastname: Laposata
authors.forename: Sarah W
authors.initials: SW
authors.lastname: Njoroge
authors.forename: Obi C
authors.initials: OC
authors.lastname: Umunakwe
authors.forename: Waddah
authors.initials: W
authors.lastname: Katrangi
authors.forename: Adam C
authors.initials: AC
authors.lastname: Seegmiller
mesh_terms: D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003550:Cystic Fibrosis / Q000378:metabolism*; D044943:Fatty Acid Desaturases / Q000235:genetics / Q000378:metabolism*; D000081031:Fatty Acid Elongases; D005231:Fatty Acids, Unsaturated / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D013230:Stearoyl-CoA Desaturase
chemical_list: D005231:Fatty Acids, Unsaturated; D007527:Isoenzymes; D044943:Fatty Acid Desaturases; D013230:Stearoyl-CoA Desaturase; C029627:delta-9 fatty acid desaturase; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases