Individual Differences in Hyperlipidemia and Vitamin E Status in Response to Chronic Alcohol Self-Administration in Cynomolgus Monkeys

Abstract

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/day for 19 months, n=11) were compared with non-drinkers (n=5, control) Results Three alcohol drinking animals developed hyperlipidemia with plasma triglyceride levels (1.8 ± 0.9 mmol/L) 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 mmol/L) 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 ± 37nmol/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). Conclusion 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.

Reversal of alcohol induced testicular hyperlipidemia by supplementation of ascorbic acid and its comparison with abstention in male guinea pigs

“…This may be due to the increased activity of HMG CoA reductase, an enzyme involved in the rate-limiting step of cholesterol biosynthesis during alcohol ingestion. This is in line with previous studies [1,34,35]. Cholesterol is a known precursor of the male hormone, testosterone, which is utilized by germ cells and is required mainly to organize the lipid bilayer of the sperm plasma membrane [36].…”

“…Testicular lipids consist of glycerides, which form the energy source of germ cells, and sterols and phospholipids, which are the primary structural components of membranes and cholesterol, which serve as the precursor for testicular steroidogenesis [31]. Chronic alcohol intake is known to cause hyperlipidemia both in man and animals [1]. Consistent with this observation, our study also showed that excessive alcohol et al [42] and Awano et al [43] reported that phospholipids serve as substrates for spermatozoa during their development and maturation; therefore, the rise in total testicular phospholipids in alcohol-treated animals observed in this study could be due to a decreased rate of utilization of these compounds as a result of germinal cell depletion.…”

“…Prolonged exposure to alcohol is known to increase the levels of lipids, leading to hyperlipidemia [1]. Ethanol is metabolized via alcohol dehydrogenase (ADH) as well as by cytochrome P450 enzymes that are part of the microsomal ethanol-oxidizing system [2].…”

Synaptic and Morphological Neuroadaptations in the Putamen Associated with Long-Term, Relapsing Alcohol Drinking in Primates

“…Chronic alcohol intakes also result in adverse physiological consequences to the liver, heart, blood, and brain (Carden et al , 2006; Hemby et al , 2006; Walker and Grant, 2006; Freeman et al , 2006; Ivester et al , 2007; Acosta et al , 2010; Cheng et al , 2010; Freeman et al , 2010; Lebold et al , 2011). However, the effects of a multi-year protocol of EtOH self-administration with repeated abstinence have not been reported, and we hypothesized that adaptations in aspects of striatal function likely contributes to stereotyped heavy drinking behavior.…”

Plasma proteomic alterations in non-human primates and humans after chronic alcohol self-administration

“…While there is growing evidence for a role of RBP4 expression in obesity-induced diabetes (Yang et al, 2005), no previous data regarding circulating levels of RBP4 with excessive alcohol intake is present in the literature. However, a relationship between vitamin homeostasis and regulation of lipid levels with excessive alcohol intake has been observed in this non-human primate model and may integrate the roles of vitamin status, lipoprotein levels, and inflammatory processes in alcohol related pathology (Lebold et al, 2010). Like ITIH4, the changes in RBP4 levels observed in monkeys were not evident in the human subjects examined.…”