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Journal of Lipid Research, Vol. 50, 154-161, January 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Patient-Oriented and Epidemiological Research

Compartmental analysis of plasma and liver n-3 essential fatty acids in alcohol-dependent men during withdrawal

Robert J. Pawlosky^1,*, Joseph R. Hibbeln, David Herion, David E. Kleiner^** and Norman Salem, Jr.

^* Laboratory of Metabolic Control, National Cancer Institute NIH, Bethesda, MD
Laboratory of Membrane Biochemistry & Biophysics, National Cancer Institute NIH, Bethesda, MD
Laboratory of Clinical and Translational Studies National Institutes on Alcohol Abuse & Alcoholism, National Cancer Institute NIH, Bethesda, MD
^** Laboratory of Pathology, National Cancer Institute NIH, Bethesda, MD

Published, JLR Papers in Press, August 22, 2008.

¹ To whom correspondence should be addressed. e-mail: bpawl{at}niaaa.nih.gov

The mechanism by which chronic ethanol consumption reduces concentrations of long chain polyunsaturated (LCP) fatty acids (FA) in tissues of humans was investigated in alcohol-dependent (AD) men during early withdrawal and to a well-matched control group by fitting the concentration-time curves of d₅-labeled n-3 FA from plasma and liver, which originated from an oral dose of d₅-linolenic acid (d₅-18:3n-3) ethyl ester to a compartmental model. Blood sampled over 168 h and a liver specimen obtained 96 h after isotope administration were analyzed for d₅-18:3n-3, d₅-20:5n-3, d₅-22:5n-3, and d₅-22:6n-3. Plasma 20:5n-3 and 22:5n-3 were lower in AD subjects, compared with controls (20:5n-3: -50%, 22:5n-3: -34%). Increased amounts of d₅-18:3n-3 were directed toward synthesis of d₅-20:5n-3 in AD subjects (P < .05). However, this effect was offset by larger amounts of 20:5n-3 lost from plasma (control: 2.0 vs. AD: 4.2 mg d^–1). In livers of AD subjects, more d₅-18:3n-3 and d₅-22:5n-3 were utilized for synthesis of d₅-20:5n-3 (+200%) and d₅-22:6n-3 (+210%), respectively, than was predicted from plasma kinetics. Although, the potential to utilize linolenic acid for synthesis of LCP FA was greater in AD subjects compared with controls, heightened disappearance rates of 20:5n-3 reduced overall plasma concentrations of several endogenous n-3 LCP FA.

Supplementary key words ethanol • -linolenic acid • docosahexaenoic acid • isotope tracer • compartmental modeling • d₅-fatty acids • eicosapentaenoic acid • cigarette smoking

Abbreviations: AD, alcohol-dependent; CRN, Clinical Research Network; LCP, long chain polyunsaturated; MAST, Michigan Alcoholism Screening Test; NASH, nonalcoholic steatohepatitis; PFB, pentafluorobenzyl; SCID, Structured Clinical Interview for Diagnosis

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