The effects of EPA, DHA, and aspirin ingestion on plasma lysophospholipids and autotaxin.
Lysophophatidylcholine (LPC) and lysophosphatidic acid (LPA) are potent lysolipid mediators increasingly linked with atherosclerosis and inflammation. A current model proposing that plasma LPA is produced when LPC is hydrolyzed by the enzyme autotaxin has not been rigorously investigated in human subjects. We conducted a clinical trial of eicosapentaenoic acid/docosahexaenoic acid (EPA/DHA) and aspirin ingestion in normal volunteers. Fasting blood samples were drawn at baseline and after 4-week supplementation with EPA/DHA (3.4 g/d) with and without aspirin (650 mg). Plasma LPC and LPA species and autotaxin activity were measured. EPA-LPC and DHA-LPC concentrations increased significantly with EPA/DHA supplementation whereas EPA- and DHA-LPA did not. Autotaxin activity was unaffected by any treatment, and aspirin had no effect on any endpoint. Taken together, our data demonstrate that plasma LPC, but not LPA, species can be dynamically regulated by dietary supplementation, and argue against a simple model of LPA generation via LPC hydrolysis.
Block
R C
RC
Department of Community and Preventive Medicine, University of Rochester School of Medicine and Dentistry, Box 644, 601 Elmwood Avenue, Rochester, New York 14642, USA. robert_block@urmc.rochester.edu
Duff
R
R
Lawrence
P
P
Kakinami
L
L
Brenna
J T
JT
Shearer
G C
GC
Meednu
N
N
Mousa
S
S
Friedman
A
A
Harris
W S
WS
Larson
Mark
M
Georas
S
S
D000328:Adult; D001241:Aspirin / Q000494:pharmacology*; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D008244:Lysophosphatidylcholines / Q000097:blood; D008246:Lysophospholipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009097:Multienzyme Complexes / Q000097:blood*; D043264:Phosphodiesterase I / Q000097:blood*; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases / Q000097:blood*; D055815:Young Adult; D000099189:Lysophospholipase D
D001241:Aspirin; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; D008244:Lysophosphatidylcholines; D008246:Lysophospholipids; D009097:Multienzyme Complexes; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases; D000099189:Lysophospholipase D; C032881:lysophosphatidic acid