The Effects of EPA, DHA, and Aspirin Ingestion on Plasma Lysophospholipids and Autotaxin

Block, R.C.; Duff, R.; Lawrence, P.; Kakinami, L.; Brenna, J.T.; Shearer, G.C.; Meednu, N.; Mousa, S.; Friedman, A.; Harris, W.S.; Larson, Mark; Georas, S.

doi:10.1016/j.plefa.2009.12.005

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Volume 82, Issue 2 , Pages 87-95, February 2010

The Effects of EPA, DHA, and Aspirin Ingestion on Plasma Lysophospholipids and Autotaxin

R.C. Block
- Department of Community and Preventive Medicine and the Cardiology Division, Department of Medicine, the University of Rochester School of Medicine and Dentistry, Box 644, 601 Elmwood Avenue, Rochester, New York 14642
- Corresponding author. Tel.: +15852753356.
R. Duff
- Pulmonary and Critical Care Division, Department of Medicine, the University of Rochester School of Medicine and Dentistry, Rochester, New York
P. Lawrence
- Division of Human Nutrition, Cornell University, Ithaca, New York
L. Kakinami
- Department of Community and Preventive Medicine and the Cardiology Division, Department of Medicine, the University of Rochester School of Medicine and Dentistry, Box 644, 601 Elmwood Avenue, Rochester, New York 14642
J.T. Brenna
- Division of Human Nutrition, Cornell University, Ithaca, New York
G.C. Shearer
- Cardiovascular Health Research Center, Sanford Research/USD, Sioux Falls, SD
N. Meednu
- Pulmonary and Critical Care Division, Department of Medicine, the University of Rochester School of Medicine and Dentistry, Rochester, New York
S. Mousa
- Pharmaceutical Research Institute, Albany College of Pharmacy, Albany, New York
A. Friedman
- Department of Environmental Medicine, the University of Rochester School of Medicine and Dentistry, Rochester, New York
W.S. Harris
- Cardiovascular Health Research Center, Sanford Research/USD, Sioux Falls, SD
Mark Larson
- Augustana College, Sioux Falls, SD
S. Georas
- Pulmonary and Critical Care Division, Department of Medicine, the University of Rochester School of Medicine and Dentistry, Rochester, New York

Received 19 October 2009; received in revised form 18 December 2009; accepted 22 December 2009. published online 27 January 2010.

Abstract

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 (3.4g/d) with and without aspirin (650mg). 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.

Keywords: Eicosapentaenoic acid, Docosahexaenoic acid, Lysophosphatidylcholine, Lysophosphatidic acid, Autotaxin, Lysophospholipase D