Fatty acid ethyl esters in human mononuclear cells: Production by endogenous synthesis greatly exceeds the uptake of preformed ethyl esters

Khaled Alhomsi, Joanne E. Cluette-Brown, Michael Laposata

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: Fatty acid ethyl esters (FAEE) are nonoxidative metabolites of ethanol. They are esterification products of ethanol and fatty acids. Fatty acid ethyl esters have been implicated as important mediators of ethanol-induced cytotoxicity, organ damage, and disease. In addition, they serve as specific and sensitive biomarkers for ethanol intake. Following ethanol consumption, FAEE are found in circulating blood bound to albumin or/and lipoproteins. Objectives: Using a mononuclear fraction of white blood cells (WBC) exposed to ethanol, we investigated FAEE synthesis. We then determined the amount of uptake of preformed FAEE presented to the cells and compared the amounts of FAEE within the cells that were derived from endogenous synthesis with the amount derived from uptake of exposure FAEE. We also measured the persistence of FAEE within these cells and assessed the fate of the FAEE-associated fatty acid upon FAEE hydrolysis. Methods: A mononuclear fraction of human WBC was incubated with 25, 50, or 100 mM ethanol for 0.08 to 120 minutes, and FAEE synthesis was measured by gas chromatography/mass spectrometry. In other experiments, mononuclear cells were incubated with 25, 50, and/or 100 μM [3H]ethyl oleate, a representative FAEE species, for 0.08-120 minutes, and FAEE uptake and hydrolysis were measured. Results: The total FAEE formed by treating the cells with 25 mM ethanol, which represents a physiologic dose achievable with excess alcohol intake, greatly exceeded the FAEE within cells derived from uptake of 100 μM ethyl oleate, which represents a supraphysiologic dose. There was hydrolysis of FAEE by human mononuclear cells, with free fatty acids as major metabolites of FAEE hydrolysis. Unlike any other cell type or homogenate studied, the only ethyl ester formed by human mononuclear cells exposed to ethanol was ethyl oleate. Conclusions: There is significant synthesis of FAEE by human mononuclear cells within seconds of exposure to physiologic doses of ethanol. The amount of FAEE in these cells derived from endogenous synthesis greatly exceeds the amount acquired by exogenous uptake.

Original languageEnglish (US)
Pages (from-to)560-566
Number of pages7
JournalAlcoholism: Clinical and Experimental Research
Volume30
Issue number3
DOIs
StatePublished - Mar 2006
Externally publishedYes

Fingerprint

Esters
Fatty Acids
Ethanol
Hydrolysis
Blood
Metabolites
Leukocytes
Cells
Esterification
Biomarkers
Cytotoxicity
Nonesterified Fatty Acids
Gas chromatography
Gas Chromatography-Mass Spectrometry
Lipoproteins
Mass spectrometry

Keywords

  • Ethanol
  • Ethyl Oleate
  • Fatty Acid Ethyl Esters
  • Free Fatty Acids
  • Human Mononuclear Cells

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology

Cite this

Fatty acid ethyl esters in human mononuclear cells : Production by endogenous synthesis greatly exceeds the uptake of preformed ethyl esters. / Alhomsi, Khaled; Cluette-Brown, Joanne E.; Laposata, Michael.

In: Alcoholism: Clinical and Experimental Research, Vol. 30, No. 3, 03.2006, p. 560-566.

Research output: Contribution to journalArticle

@article{f1ed3e95a2b34ddebb8dea339a33fd21,
title = "Fatty acid ethyl esters in human mononuclear cells: Production by endogenous synthesis greatly exceeds the uptake of preformed ethyl esters",
abstract = "Background: Fatty acid ethyl esters (FAEE) are nonoxidative metabolites of ethanol. They are esterification products of ethanol and fatty acids. Fatty acid ethyl esters have been implicated as important mediators of ethanol-induced cytotoxicity, organ damage, and disease. In addition, they serve as specific and sensitive biomarkers for ethanol intake. Following ethanol consumption, FAEE are found in circulating blood bound to albumin or/and lipoproteins. Objectives: Using a mononuclear fraction of white blood cells (WBC) exposed to ethanol, we investigated FAEE synthesis. We then determined the amount of uptake of preformed FAEE presented to the cells and compared the amounts of FAEE within the cells that were derived from endogenous synthesis with the amount derived from uptake of exposure FAEE. We also measured the persistence of FAEE within these cells and assessed the fate of the FAEE-associated fatty acid upon FAEE hydrolysis. Methods: A mononuclear fraction of human WBC was incubated with 25, 50, or 100 mM ethanol for 0.08 to 120 minutes, and FAEE synthesis was measured by gas chromatography/mass spectrometry. In other experiments, mononuclear cells were incubated with 25, 50, and/or 100 μM [3H]ethyl oleate, a representative FAEE species, for 0.08-120 minutes, and FAEE uptake and hydrolysis were measured. Results: The total FAEE formed by treating the cells with 25 mM ethanol, which represents a physiologic dose achievable with excess alcohol intake, greatly exceeded the FAEE within cells derived from uptake of 100 μM ethyl oleate, which represents a supraphysiologic dose. There was hydrolysis of FAEE by human mononuclear cells, with free fatty acids as major metabolites of FAEE hydrolysis. Unlike any other cell type or homogenate studied, the only ethyl ester formed by human mononuclear cells exposed to ethanol was ethyl oleate. Conclusions: There is significant synthesis of FAEE by human mononuclear cells within seconds of exposure to physiologic doses of ethanol. The amount of FAEE in these cells derived from endogenous synthesis greatly exceeds the amount acquired by exogenous uptake.",
keywords = "Ethanol, Ethyl Oleate, Fatty Acid Ethyl Esters, Free Fatty Acids, Human Mononuclear Cells",
author = "Khaled Alhomsi and Cluette-Brown, {Joanne E.} and Michael Laposata",
year = "2006",
month = "3",
doi = "10.1111/j.1530-0277.2006.00062.x",
language = "English (US)",
volume = "30",
pages = "560--566",
journal = "Alcoholism: Clinical and Experimental Research",
issn = "0145-6008",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Fatty acid ethyl esters in human mononuclear cells

T2 - Production by endogenous synthesis greatly exceeds the uptake of preformed ethyl esters

AU - Alhomsi, Khaled

AU - Cluette-Brown, Joanne E.

AU - Laposata, Michael

PY - 2006/3

Y1 - 2006/3

N2 - Background: Fatty acid ethyl esters (FAEE) are nonoxidative metabolites of ethanol. They are esterification products of ethanol and fatty acids. Fatty acid ethyl esters have been implicated as important mediators of ethanol-induced cytotoxicity, organ damage, and disease. In addition, they serve as specific and sensitive biomarkers for ethanol intake. Following ethanol consumption, FAEE are found in circulating blood bound to albumin or/and lipoproteins. Objectives: Using a mononuclear fraction of white blood cells (WBC) exposed to ethanol, we investigated FAEE synthesis. We then determined the amount of uptake of preformed FAEE presented to the cells and compared the amounts of FAEE within the cells that were derived from endogenous synthesis with the amount derived from uptake of exposure FAEE. We also measured the persistence of FAEE within these cells and assessed the fate of the FAEE-associated fatty acid upon FAEE hydrolysis. Methods: A mononuclear fraction of human WBC was incubated with 25, 50, or 100 mM ethanol for 0.08 to 120 minutes, and FAEE synthesis was measured by gas chromatography/mass spectrometry. In other experiments, mononuclear cells were incubated with 25, 50, and/or 100 μM [3H]ethyl oleate, a representative FAEE species, for 0.08-120 minutes, and FAEE uptake and hydrolysis were measured. Results: The total FAEE formed by treating the cells with 25 mM ethanol, which represents a physiologic dose achievable with excess alcohol intake, greatly exceeded the FAEE within cells derived from uptake of 100 μM ethyl oleate, which represents a supraphysiologic dose. There was hydrolysis of FAEE by human mononuclear cells, with free fatty acids as major metabolites of FAEE hydrolysis. Unlike any other cell type or homogenate studied, the only ethyl ester formed by human mononuclear cells exposed to ethanol was ethyl oleate. Conclusions: There is significant synthesis of FAEE by human mononuclear cells within seconds of exposure to physiologic doses of ethanol. The amount of FAEE in these cells derived from endogenous synthesis greatly exceeds the amount acquired by exogenous uptake.

AB - Background: Fatty acid ethyl esters (FAEE) are nonoxidative metabolites of ethanol. They are esterification products of ethanol and fatty acids. Fatty acid ethyl esters have been implicated as important mediators of ethanol-induced cytotoxicity, organ damage, and disease. In addition, they serve as specific and sensitive biomarkers for ethanol intake. Following ethanol consumption, FAEE are found in circulating blood bound to albumin or/and lipoproteins. Objectives: Using a mononuclear fraction of white blood cells (WBC) exposed to ethanol, we investigated FAEE synthesis. We then determined the amount of uptake of preformed FAEE presented to the cells and compared the amounts of FAEE within the cells that were derived from endogenous synthesis with the amount derived from uptake of exposure FAEE. We also measured the persistence of FAEE within these cells and assessed the fate of the FAEE-associated fatty acid upon FAEE hydrolysis. Methods: A mononuclear fraction of human WBC was incubated with 25, 50, or 100 mM ethanol for 0.08 to 120 minutes, and FAEE synthesis was measured by gas chromatography/mass spectrometry. In other experiments, mononuclear cells were incubated with 25, 50, and/or 100 μM [3H]ethyl oleate, a representative FAEE species, for 0.08-120 minutes, and FAEE uptake and hydrolysis were measured. Results: The total FAEE formed by treating the cells with 25 mM ethanol, which represents a physiologic dose achievable with excess alcohol intake, greatly exceeded the FAEE within cells derived from uptake of 100 μM ethyl oleate, which represents a supraphysiologic dose. There was hydrolysis of FAEE by human mononuclear cells, with free fatty acids as major metabolites of FAEE hydrolysis. Unlike any other cell type or homogenate studied, the only ethyl ester formed by human mononuclear cells exposed to ethanol was ethyl oleate. Conclusions: There is significant synthesis of FAEE by human mononuclear cells within seconds of exposure to physiologic doses of ethanol. The amount of FAEE in these cells derived from endogenous synthesis greatly exceeds the amount acquired by exogenous uptake.

KW - Ethanol

KW - Ethyl Oleate

KW - Fatty Acid Ethyl Esters

KW - Free Fatty Acids

KW - Human Mononuclear Cells

UR - http://www.scopus.com/inward/record.url?scp=33644768156&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33644768156&partnerID=8YFLogxK

U2 - 10.1111/j.1530-0277.2006.00062.x

DO - 10.1111/j.1530-0277.2006.00062.x

M3 - Article

C2 - 16499498

AN - SCOPUS:33644768156

VL - 30

SP - 560

EP - 566

JO - Alcoholism: Clinical and Experimental Research

JF - Alcoholism: Clinical and Experimental Research

SN - 0145-6008

IS - 3

ER -