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Increased Elongase 6 and Δ9‐Desaturase Activity are Associated with n‐7 and n‐9 Fatty Acid Changes in Cystic Fibrosis
Author(s) -
Thomsen Kelly F.,
Laposata Michael,
Njoroge Sarah W.,
Umunakwe Obi C.,
Katrangi Waddah,
Seegmiller Adam C.
Publication year - 2011
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/s11745-011-3563-z
Subject(s) - clinical chemistry , cystic fibrosis , enzyme , pathogenesis , lipidology , fatty acid , fatty acid metabolism , fatty acid desaturase , lipid metabolism , metabolism , biochemistry , biology , medicine , endocrinology , stearoyl coa desaturase , chemistry , gene , gene expression , polyunsaturated fatty acid
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.