Contributions of different fatty acid sources to very low-density lipoprotein-triacylglycerol in the fasted and fed states

Context: The liver's regulation of fatty acids (FAs) postprandially may contribute to risk of metabolic diseases. Objective: Measurements of steady-state metabolism were used to investigate sources of FAs used for very low-density lipoprotein ( VLDL)-triacylglycerol (TG) synthesis during fasting and feeding in vivo. Design/Intervention: Subjects were duodenally fed a formula labeled with the stable isotope glyceryl tri-palmitate-d(31) and iv infused with [1,2,3,4-C-13(4)]-palmitatic acid and [1-C-13(1)]-acetate to quantitate the liver's use of FAs originating from adipose tissue and de novo lipogenesis. Setting/Participants: This study of healthy men ( n = 12; body mass index, 24.4 +/- 2.7 kg/m(2)) was conducted at a General Clinical Research Center. Main Outcome Measures: Concentrations of metabolites during fasting and feeding, sources of FAs used for lipoprotein synthesis, rate of appearance of serum nonesterified FA (NEFA), and VLDL-TG were measured. Results: During fasting, 77.2 +/- 14.0% of VLDL-TG was derived from adipose FA recycling and 4.0 +/- 3.6% from lipogenesis; with feeding, 43.6 +/- 18.6% came from adipose FAs ( P < 0.001), 8.2 +/- 5.1% from lipogenesis ( P < 0.001), 15.2 +/- 13.7% from uptake of chylomicron-remnant TG, and 10.3 +/- 6.9% from dietary FA spillover into the serum NEFA pool. Fed-state VLDL-TG from NEFA reesterification decreased in proportion to the reduction in adipose NEFA appearance. Conclusion: These data: 1) quantify the extent to which the healthy liver manages its use of different sources of FAs that flow to it, 2) demonstrate how the postprandial reduction in adipose-NEFA flux may be partially replaced by other sources, and 3) highlight the potential for dietary FA spillover to support the continued dominance of NEFA as a substrate for VLDL-TG synthesis.