Meal composition and postprandial lipoprotein lipid sources: Effect of rate of nutrient delivery

Epidemiological and clinical studies have demonstrated that elevated postprandial (fed-state) lipemia poses an increased risk for coronary artery disease. To date, no studies have quantitated the contribution of various sources (non-esterified fatty acids (NEFA) dietary, and newly-made (de novo) fatty acids), to fed-state lipoprotein particles. The present study was designed to quantify the contributions of these fatty acid sources to very low-density lipoprotein (VLDL) triacylglycerol (TAG) following two successive liquid meals consumed by mouth (meal-feeding regimen) in healthy subjects. Comparison of these data to those obtained via tube-feeding (continuous-feeding regimen) was performed to determine if rate of substrate delivery would alter fatty acid usage by the liver. Contributions of NEFA, dietary fatty acids, and de novo lipogenesis to VLDL-TAG were quantified using stable isotopes, GC/MS, and MIDA. Contribution of NEFA to VLDL-TAG was similar under both feeding regimens although the insulin area-under-the-curve (AUC) was greater with meal-feeding (1597 +/- 455 vs. 471 +/- 484 pmol·h·L -1, P < 0.004). Under both feeding regimens, serum NEFA contributed the majority of fatty acids used for lipoprotein-TAG synthesis in both the fasted and fed states. The contribution of dietary fatty acids provided the second most abundant source of lipid for fed-state VLDL-TAG. The contribution of dietary fatty acids to VLDL-TAG increased to a significantly greater extent with meal-feeding from hours 1--5 ( P < 0.028) and 7--11 (P < 0.020). Analysis of these data as the average over the postprandial period (12.9 +/- 3.4 vs. 5.9 +/- 1.9 mumol/L, P = 0.03, meal-feeding and continuous-feeding, respectively) or by AUC (137 +/- 42 vs. 65 +/- 24 mumol·h·L-1, P = 0.05), documented the absolute amount of VLDL-TAG derived from dietary fatty acids remained significantly greater with meal-feeding. Lastly, the percentage of VLDL-TAG derived from newly-made fatty acids supported a physiologic stimulation of fatty acid synthesis more pronounced with meal-feeding. Overall, lipogenesis achieved a higher AUC with meal-feeding vs. continuous-feeding (88.7 +/- 84.4 vs. 1.9 +/- 19.3 mumol·h·L -1, P = 0.03), suggesting greater stimulation of newly-made fatty acids from increased glucose delivery rate. These data demonstrate for the first time in humans the well-coordinated use of fatty acids by the liver from the fasted to fed states, and highlight the dominant role of NEFA for VLDL-TAG synthesis in both states.