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

Abstract

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.

Keywords: Alcohol; Cholesteryl ester transfer; Dietary fat; Metabolism.

Fig. 1

Changes in plasma CETA as a function of ingestion of (a) alcohol, (b) SAT, and (c) (alcohol + SAT) among NTG and HTG subjects as labeled. Curves are shown as a fit of the data to a cubic polynomial from which the peak CETA values were extracted. Points are mean ± SEM. Significant differences between NTG and HTG at various times are indicated by asterisks (p < 0.05). Significant changes from baseline for HTG are indicated by red hashtags, and for NTG by black hashtags. CETA, cholesteryl ester transfer activity; HTG, hypertriglyceridemic; NTG, normotriglyceridemic; SAT, saturated fat

Fig. 2

Effect of standard doses of (a) alcohol, (b) SAT, and (c) (alcohol + SAT) on plasma cholesterol as labeled. Curves are a fit of the data to a cubic polynomial. Points are mean ± SEM. There were no significant differences between HTG and NTG values nor between any time points compared to baseline values. HTG, hypertriglyceridemic; NTG, normotriglyceridemic; SAT, saturated fat

Fig. 3

Effect of standard doses of (a) alcohol, (b) SAT, and (c) (alcohol + SAT) on plasma NEFA as labeled. Curves are shown as a fit of the data to a cubic polynomial; points are mean ± SEM. Significant differences between NTG and HTG at various times are indicated by asterisks (p < 0.05). Significant changes from baseline for HTG are indicated by red hashtags, and for NTG by black hashtags. HTG, hypertriglyceridemic; NTG, normotriglyceridemic; SAT, saturated fat

Fig. 4

Effect of standard doses of (a) alcohol, (b) SAT, and (c) (alcohol + SAT) on plasma TAG as labeled. Curves are shown as a fit of the data to a cubic polynomial from which the peak TAG values were extracted. Points are mean ± SEM. Significant differences between NTG and HTG at various times are indicated by asterisks (p < 0.05). Significant changes from baseline for HTG are indicated by red hashtags, and for NTG by black hashtags. HTG, hypertriglyceridemic; NTG, normotriglyceridemic; SAT, saturated fat

Fig. 5

Comparison of plasma %CETA versus plasma TAG concentration. (a) Linear regression analysis of CETA (%baseline) versus plasma TAG concentration. The single line of regression (r² = 0.23) is based on data from Figs. 1 and 4 for all subjects, alcohol and/or SAT loads, and time points. (b–d) Comparison of the %CETA versus absolute plasma TAG concentration following (b) alcohol, (c) SAT, and (d) (alcohol + SAT). The linear regression slope for (alcohol + SAT) is significantly lower than that for SAT-only (p < 0.001). The slope for SAT only is close to significance vs alcohol-only (p = 0.08), while the slopes for alcohol-only and (alcohol + SAT) are not different (p = 0.371). CETA, cholesteryl ester transfer activity; SAT, saturated fat; TAG, triacylglycerol