Evidence of increased flux to n-6 docosapentaenoic acid in phospholipids of pancreas from cftr-/- knockout mice.
An association has been reported between alterations in fatty acid metabolism and cystic fibrosis (CF). We hypothesized that these alterations are specific for a particular lipid component(s) and are the result of a specific metabolic defect. The different lipid classes were examined for fatty acid changes by using pancreatic homogenates and primary cultures of pancreatic acini from cftr(-/-) (CF) and wild-type mice. Lipid classes and phospholipids were separated by aminopropyl column chromatography and high-performance liquid chromatography, and fatty acid methyl esters were analyzed. The results indicate that in CF mice (1) linoleate was decreased in phospholipids but not in neutral lipids; (2) there was an increase in dihomo-gamma-linolenate and in docosapentaenoate, the terminal fatty acid of the n-6 pathway, in total lipids and total phospholipids, but not in the neutral lipid class; and (3) the docosapentaenoate (n-6)/docosahexaenoate (n-3) ratio was significantly elevated in neutral phospholipids. This suggests an enhanced flux through the n-6 pathway beyond arachidonate. This study provides a more in-depth understanding of the fatty acid alterations found in CF, as reflected by the cftr(-/-) mouse model.
Ollero
Mario
M
Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA.
Laposata
Michael
M
Zaman
Munir M
MM
Blanco
Paola G
PG
Andersson
Charlotte
C
Zeind
John
J
Urman
Yana
Y
Kent
Geraldine
G
Alvarez
Juan G
JG
Freedman
Steven D
SD
D000818:Animals; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003550:Cystic Fibrosis / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000172:deficiency; D043371:Fatty Acids, Omega-6 / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D019787:Linoleic Acid / Q000032:analysis; D008055:Lipids / Q000032:analysis; D051379:Mice; D018181:Mice, Inbred CFTR; D010179:Pancreas / Q000378:metabolism*; D010743:Phospholipids / Q000032:analysis* / Q000737:chemistry
D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D008055:Lipids; D010743:Phospholipids; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D019787:Linoleic Acid; C026219:docosapentaenoic acid