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

J Clin Endocrinol Metab. 2006 Apr;91(4):1446-52. doi: 10.1210/jc.2005-1709. Epub 2006 Jan 31.


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.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism
  • Adult
  • Blood Glucose / metabolism
  • Chylomicrons / metabolism
  • Diet
  • Fasting / metabolism*
  • Fatty Acids / pharmacokinetics
  • Fatty Acids / pharmacology*
  • Fatty Acids, Nonesterified / blood
  • Female
  • Gas Chromatography-Mass Spectrometry
  • Humans
  • Insulin / blood
  • Lipoproteins, VLDL / blood*
  • Male
  • Middle Aged
  • Postprandial Period
  • Radiopharmaceuticals / pharmacokinetics
  • Triglycerides / blood*


  • Blood Glucose
  • Chylomicrons
  • Fatty Acids
  • Fatty Acids, Nonesterified
  • Insulin
  • Lipoproteins, VLDL
  • Radiopharmaceuticals
  • Triglycerides