Dietary Alcohol and Fat Differentially Affect Plasma Cholesteryl Ester Transfer Activity and Triglycerides in Normo- and Hypertriglyceridemic Subjects

Moderate alcohol consumption is associated with increased plasma high-density lipoprotein (HDL)-cholesterol concentrations and reduced risk for cardiovascular disease. Plasma cholesteryl ester transfer activity (CETA) mediates the exchange of HDL-cholesteryl ester (CE) for the triacylglycerol (TAG) of very-low-density lipoproteins. We compared the effects of oral challenges of Alcohol, saturated fat (SAT), and (Alcohol + SAT) on plasma CETA, cholesterol, nonesterified fatty acids (NEFA), and TAG among normo-triglyceridemic (NTG) and mildly hypertriglyceridemic (HTG) volunteers having a range of plasma TAG concentrations. The major changes were (1) CETA increased more after ingestion of SAT and (Alcohol + SAT) in the HTG group versus the NTG group; (2) after all three challenges, elevation of plasma TAG concentration persisted longer in the HTG versus NTG group. Plasma cholesterol was not affected by the three dietary challenges, while Alcohol increased NEFA more in the HTG group than the NTG group. Plasma TAG best predicted plasma CETA, suggesting that intestinally derived lipoproteins are acceptors of HDL-CE. Unexpectedly, ingestion of (Alcohol + SAT) reduced the strength of the correlation between plasma TAG and CETA, that is the effects of (SAT and Alcohol) on plasma CETA are not synergistic nor additive but rather mutually suppressive. The alcohol-mediated inhibition of CE-transfer to chylomicrons maintains a higher plasma HDL-cholesterol concentration, which is athero-protective, although the suppressive metabolite underlying this correlation could be acetate, the terminal alcohol metabolite, other factors, including CETA inhibitors, are also likely important.