TY - JOUR
T1 - Increased elongase 6 and Δ9-desaturase activity are associated with n-7 and n-9 fatty acid changes in cystic fibrosis
AU - Thomsen, Kelly F.
AU - Laposata, Michael
AU - Njoroge, Sarah W.
AU - Umunakwe, Obi C.
AU - Katrangi, Waddah
AU - Seegmiller, Adam C.
N1 - Funding Information:
Acknowledgments The authors thank Jesse Gilliam for technical assistance and Eva Henderson and the Vanderbilt Molecular Cell Biology Core Laboratory for primer design and testing and qRT-PCR support. This work was funded in part by Clinical Translational Science Award 1UL-1RR024975 from the National Center for Research Resources and Training Grant in Gastroenterology 5T32DK007673-18 from the National Institutes of Health to K.F.T., the Edward and Nancy Fody Endowed Chair in Pathology (M.L.), and the Vanderbilt Physician Scientist Training Program (A.C.S.).
PY - 2011/8
Y1 - 2011/8
N2 - 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.
AB - 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.
KW - Cystic fibrosis
KW - Desaturases
KW - Elongases
KW - Fatty acid metabolism
KW - Gene expression
KW - Monounsaturated fatty acids
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U2 - 10.1007/s11745-011-3563-z
DO - 10.1007/s11745-011-3563-z
M3 - Article
C2 - 21544602
AN - SCOPUS:79961209660
SN - 0024-4201
VL - 46
SP - 669
EP - 677
JO - Lipids
JF - Lipids
IS - 8
ER -