Long-term ethanol consumption impairs reverse cholesterol transport function of high-density lipoproteins by depleting high-density lipoprotein sphingomyelin both in rats and in humans.
Moderate alcohol consumption has been linked to lower incidence of coronary artery disease due to increased plasma high-density lipoprotein (HDL), whereas heavy drinking has the opposite effect. Because of the crucial role of HDL in reverse cholesterol transport and positive correlation of HDL sphingomyelin (SM) content with cholesterol efflux, we have compared HDL SM content with its reverse cholesterol transport capacity both in rats fed ethanol on long-term basis and alcoholic individuals. In rats, SM HDL content was decreased in the ethanol group (-15.4%, P < .01) with a concomitant efflux decrease (-21.0%, P < .01) compared to that in controls. Similarly, HDL from the ethanol group, when compared with HDL from the control group, exhibited 13.8% (P < .05) less cholesterol uptake with control-group hepatocytes and 35.0% (P < .05) less cholesterol uptake with ethanol-group hepatocytes. Conversely, hepatocytes from the ethanol group, when compared with hepatocytes from the control group, exhibited 31.0% (P < .01) less cholesterol uptake with control-group HDL and 48.0% (P < .01) less with ethanol-group HDL. In humans, SM content in plasma HDL was also decreased in chronically alcoholic individuals without liver disease (-51.5%, P < .01) and in chronically alcoholic individuals with liver disease (-51.3%, P < .01), compared with nondrinkers. Concomitantly, in alcoholic individuals without liver disease, both efflux and uptake were decreased by 83.0% and 54.0% (P < .01), respectively, and in chronically alcoholic individuals with liver disease by 84.0% and 61.0% (P < .01), respectively, compared with nondrinkers. Based on these findings, we conclude that long-term ethanol consumption significantly impairs not only cholesterol efflux function of HDL by decreasing its SM content but also cholesterol uptake by affecting presumably hepatocyte receptors for HDL.
Marmillot
Philippe
P
Lipid Research Laboratory, Veterans Affairs Medical Center, The George Washington University, Washington, DC 20422, USA.
Munoz
Jennifer
J
Patel
Sanket
S
Garige
Mamatha
M
Rosse
Richard B
RB
Lakshman
M Raj
MR
D000328:Adult; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism*; D000431:Ethanol / Q000633:toxicity*; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D008075:Lipoproteins, HDL / Q000032:analysis / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D051381:Rats; D011920:Rats, Inbred WF; D013109:Sphingomyelins / Q000032:analysis*
D008075:Lipoproteins, HDL; D013109:Sphingomyelins; D000431:Ethanol; D002784:Cholesterol