Individual differences in hyperlipidemia and vitamin E status in response to chronic alcohol self-administration in cynomolgus monkeys.
BACKGROUND
Chronic ethanol self-administration induces oxidative stress and exacerbates lipid peroxidation. α-Tocopherol is a potent lipid antioxidant and vitamin that is dependent upon lipoprotein transport for tissue delivery.


METHODS
To evaluate the extent to which vitamin E status is deranged by excessive alcohol consumption, monkeys voluntarily drinking ethanol (1.36 to 3.98 g/kg/d for 19 months, n = 11) were compared with nondrinkers (n = 5, control).


RESULTS
Three alcohol-drinking animals developed hyperlipidemia with plasma triglyceride levels (1.8 ± 0.9 mM) double those of normolipidemic (NL) drinkers (0.6 ± 0.2) and controls (0.6 ± 0.3, p < 0.05); elevated plasma cholesterol (3.6 ± 0.5 mM) compared with NL drinkers (2.3 ± 0.2, p < 0.05) and controls (2.9 ± 0.3); and lower plasma α-tocopherol per triglycerides (14 ± 6 mmol/mol) than controls (27 ± 8) and NL drinkers (23 ± 6, p < 0.05). Hyperlipidemic monkey liver α-tocopherol (47 ± 15 nmol/g) was lower than NL drinkers (65 ± 13) and controls (70 ± 15, p = 0.080), as was adipose α-tocopherol (84 ± 37 nmol/g) compared with controls (224 ± 118) and NL drinkers (285 ± 234, p < 0.05). Plasma apolipoprotein (apo) CIII increased compared to baseline at both 12 and 19 months in the normolipidemic (p = 0.0016 and p = 0.0028, respectively) and in the hyperlipidemic drinkers (p < 0.05 and p < 0.05, respectively). Plasma apo H concentrations at 19 months were elevated hyperlipidemics (p < 0.05) relative to concentrations in control animals. C-reactive protein (CRP), a marker of inflammation, was increased compared to baseline at both the 12- and 19-month time points in the normolipidemic (p = 0.005 and p = 0.0153, respectively) and hyperlipidemic drinkers (p = 0.016 and p = 0.0201, respectively).


CONCLUSIONS
A subset of alcohol-drinking monkeys showed a predisposition to alcohol-induced hyperlipidemia. The defect in lipid metabolism resulted in lower plasma α-tocopherol per triglycerides and depleted adipose tissue α-tocopherol, and thus decreased vitamin E status.
Linus Pauling Institute, Oregon State University, Corvallis, 97331-6512, USA.
Katie M
KM
Lebold
Kathleen A
KA
Grant
Willard M
WM
Freeman
Kristine M
KM
Wiren
Galen W
GW
Miller
Caitlin
C
Kiley
Scott W
SW
Leonard
Maret G
MG
Traber
D000428:Alcohol Drinking / Q000097:blood*; D000437:Alcoholism / Q000097:blood / Q000150:complications; D000818:Animals; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D006949:Hyperlipidemias / Q000097:blood* / Q000209:etiology; D007206:Individuality; D008252:Macaca fascicularis; D012646:Self Administration; D014810:Vitamin E / Q000097:blood*; D024502:alpha-Tocopherol / Q000097:blood
D014810:Vitamin E; D000431:Ethanol; D024502:alpha-Tocopherol