Association of postalimentary lipemia with atherosclerotic manifestations

Abstract

We identified different lipemic and metabolic responses after the ingestion of a standardized meal by healthy adults and related them to atherosclerotic markers. Samples from 60 normolipidemic adults were collected before and after a liquid meal (40 g fat/m² body surface) at 0, 2, 4, 6, and 8 h for measurements of lipids, free fatty acids (FFA), insulin, cholesteryl ester transfer protein (CETP), autoantibodies to epitopes of oxidized LDL (oxLDL Ab), lipolytic activities, and apolipoprotein E polymorphism. Mean carotid intima-media thickness (cIMT) was determined by Doppler ultrasound. The volunteers were classified into early (N = 39) and late (N = 31) triacylglycerol (TAG) responders to the test meal. Late responders showed lower HDL cholesterol concentration at fasting and in the TAG peak, lower insulin and higher FFA concentrations compared to early responders. Multivariate regression analyses showed that mean cIMT was associated with gender (male) and age in early responders and by cholesterol levels at the 6th hour in late responders. oxLDL Ab were explained by lipoprotein lipase and negatively by hepatic lipase and oxLDL Ab (fasting period) by CETP (negative) and FFA (positive). This study is the first to identify a postalimentary insulin resistance state, combined with a reduced CETP response exclusively among late responders, and the identification of the regulators of postalimentary atherogenicity. Further research is required to determine the metabolic mechanisms described in the different postalimentary phenotypes observed in this study, as well as in different pathological states, as currently investigated in our laboratory.

Figure 1.. Plasma triacylglycerol (TAG) response groups and triacylglycerol areas under the curves (AUC) and areas under the incremental curves (AUIC) after a standardized fat meal. Data are reported as means ± SEM. Number of subjects per group: early responders = 39; late responders = 21; biphasic responders = 10. Wilcoxon test. A, TAG response groups: during the fasting period (FP, 0 h), 2, 4, 6, and 8 h by group; all individuals (N = 60): ¹P ≤ 0.0002, TAG increased from FP to 2, 4, 6, and 8 h; early responders: ²P ≤ 0.00001, TAG increased from fasting to 2, to 4 and to 6 h; late responders: ³P ≤ 0.0033, TAG increased from FP to 2, 4, 6, and 8 h; biphasic responders: ⁴P ≤ 0.017, TAG increased from FP to 2, 4, 6, and 8 h. TAG during fasting, at 2 h and at peaks among groups were not significant; ⁵P ≤ 0.0169, TAG at 4 h, higher in early than in late and biphasic responders; ⁶P ≤ 0.045, TAG at 6 h, lower in early than in late responders; ⁷P ≤ 0.0022, TAG at 8 h, lower in early than in late and biphasic responders (ANOVA followed by the post hoc Duncan test). B, TAG AUC and AUIC by group (mg·dL⁻¹·h⁻¹). Results not significant among groups.

Figure 2.. Postalimentary plasma free fatty acids (FFA), insulin and cholesteryl ester transfer protein (CETP) after a standardized meal. Data are reported as means ± SEM. N = minimum to maximum number of subjects with parameters determined. Wilcoxon and ANOVA with post hoc Duncan tests. A, FFA: all individuals [N = 54 subjects in the fasting period (FP), 4th and 8th hours; N = 52 at the 2nd hour and N = 51 at the 6th hour], ¹P ≤ 0.008, FFA decreased from baseline to the 2nd and 4th hours, and increased to the 8th hour; early responders (N = 37 subjects in the FP and at the 4th and 8th hours; N = 35 at 2nd hour and N = 34 at 6th hour), ²P ≤ 0.045, FFA increased from baseline to the 8th hour; late responders (N = 17, all times), ³P ≤ 0.04, FFA decreased from baseline to the 2nd hour, ⁴P ≤ 0.005 to the 4th hour, and ⁵P ≤ 0.012 FFA increased to the 8th hour; early responders: ⁶P ≤ 0.00001 at the 4th hour higher than late and biphasic responders (N = 7, all times). B, Insulin: ¹P ≤ 0.00001, ²P ≤ 0.00001, ³P ≤ 0.0009, ⁴P ≤ 0.018, respectively, in all individuals (N = 47 in FP and N = 45 in TAG peak), early responders (N = 31 in FP and N = 29 in TAG peak), late responders (N = 16 in FP and TAG peak), and biphasic responders (N = 7 in FP and TAG peak), insulin increased from baseline to the 4th hour; early responders: ⁵P ≤ 0.00001, higher peak than in late and biphasic responders. C, CETP: in all individuals (N = 54 subjects in FP and N = 48 in TAG peak), early responders (N = 37 in FP and N = 33 in TAG peak) and late responders (N = 17 in FP and N = 15 in TAG peak), CETP increased from baseline to the 4th hour: ¹P ≤ 0.0003, ²P ≤ 0.002, ³P ≤ 0.044, respectively (Wilcoxon test). Biphasic (N = 7 subjects in FP and TAG peak): results not significant at 4th hour.