Alcohol produces dose-dependent antiatherogenic and atherogenic plasma lipoprotein responses.
A comprehensive assessment of lipoprotein compositional/metabolic response to incremental caloric ethanol (EtOH) doses ranging from low to moderate to high was undertaken using male squirrel monkeys. Control monkeys were maintained on a chemically defined, isocaloric liquid diet, while experimental primates wee fed increasing doses of alcohol (6, 12, 18, 24, 30, and 36% of energy) substituted isocalorically for carbohydrate at 3-month intervals. Liver function tests and plasma triglyceride were normal for all animals. Plasma cholesterol showed a transient increase at the 12% caloric dose that was attributed solely to an increase in high density lipoprotein (HDL). A more pronounced increase in plasma sterol, beginning at 24% and continuing to 36% EtOH, was the result of increments in both HDL and low density lipoprotein (LDL) cholesterol, although the contribution by the latter was substantial primarily at the 36% dose. Plasma apolipoprotein elevations (HDL apolipoprotein A-I, LDL apolipoprotein B) generally accompanied the lipoprotein lipid increases, although the first atherogenic response for LDL became manifest as a significant increase in apolipoprotein B at 18% EtOH calories. Postheparin plasma lipoprotein lipase was not affected by dietary alcohol, whereas hepatic triglyceride lipase activity showed significant increases at higher (24 and 36%) EtOH doses. Plasma lecithin-cholesterol acyltransferase activity was normal at the 6 and 12% EtOH doses, but exhibited a significant reduction beginning at 18% and continuing to 36% EtOH. Alterations in these key lipoprotein regulatory enzymes may represent the underlying metabolic basis for the observed changes in lipoprotein levels and our earlier findings of HDL2/HDL3 subfraction modifications. Results from our study indicate that in squirrel monkeys, moderate (12%) EtOH caloric intake favors an antiatherogenic lipoprotein profile (increases HDL, normal LDL levels, and lecithin-cholesterol acyltransferase activity), whereas higher doses (24-36%) produce both coronary-protective (increases HDL) and atherogenic (increases LDL) responses. Moreover, the 18% EtOH level represents an important transition dose which signals early adverse alterations in lipoprotein composition (increases apolipoprotein B) and metabolism (decreases lecithin-cholesterol acyltransferase).
Hojnacki
J L
JL
Department of Biological Sciences, University of Lowell, Massachusetts 01854.
Cluette-Brown
J E
JE
Deschenes
R N
RN
Mulligan
J J
JJ
Osmolski
T V
TV
Rencricca
N J
NJ
Barboriak
J J
JJ
D000818:Animals; D001053:Apolipoproteins / Q000097:blood; D001161:Arteriosclerosis / Q000097:blood*; D002784:Cholesterol / Q000097:blood; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D008071:Lipoprotein Lipase / Q000097:blood; D008075:Lipoproteins, HDL / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000097:blood; D012453:Saimiri
D001053:Apolipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D000431:Ethanol; D002784:Cholesterol; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D008071:Lipoprotein Lipase