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-(13)C(4)-palmitatic acid and 1-(13)C(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.