IL-6 cooperates with peroxisome proliferator-activated receptor-α-ligands to induce liver fatty acid binding protein (LFABP) up-regulation

Liver Int. 2013 Aug;33(7):1019-28. doi: 10.1111/liv.12156. Epub 2013 Mar 28.


Background: LFABP plays a critical role in the uptake and intracellular transport of fatty acids (FA) and other peroxisome proliferator-activated receptor alpha (PPARα) ligands. PPARα activation by PPARα ligands bound to LFABP results in gene expression of FA oxidation enzymes and de novo LFABP. The cytokine IL-6 is involved in regulating liver lipid oxidation.

Aims: To study the ability of IL-6 to modulate the expression of the LFABP in hepatocytes.

Methods: HepG2 and mouse primary hepatocytes were used to test LFABP mRNA and protein expression after IL-6 and PPARα-ligand treatments. Mice lacking IL-6 and wild-type C57Bl/6 were subjected to a fasting/re-feeding cycle to monitor hepatic LFABP mRNA kinetics after food intake.

Results: In hepatocyte cultures, IL-6 treatment stimulated a LFABP mRNA sustained expression. Combined treatment of IL-6 plus PPARα ligands further enhanced LFABP gene and protein expression. In contrast, pretreatment with the PPARα-antagonist GW-6471 prevented the up-regulation of LFABP mRNA induced by IL-6 in the late phase of LFABP kinetics. Furthermore, the up-regulation of LFABP mRNA observed in the liver of wild-type mice 8 h after re-feeding was absent in mice lacking IL-6.

Conclusions: IL-6 induces LFABP kinetics in hepatocytes and is partially dependent on PPARα. The maximum increase in LFABP expression occurs when the stimulation with IL-6 and PPARα-ligands takes place simultaneously. The in vivo results indicate a postprandial regulation of LFABP that correlates with the presence of IL-6. These effects may have important implications in the postprandial increase in FA uptake and intracellular trafficking in the liver.

Keywords: GW-6471; LFABP; PPARα; WY-14,643; hepatocyte; interleukin 6; oleoylethanolamide (OEA).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Blotting, Western
  • DNA Primers / genetics
  • Fatty Acid-Binding Proteins / metabolism*
  • Fatty Acids / metabolism
  • Gene Expression Regulation / physiology*
  • Hep G2 Cells
  • Hepatocytes / metabolism*
  • Humans
  • Interleukin-6 / metabolism*
  • Interleukin-6 / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • PPAR alpha / drug effects
  • PPAR alpha / metabolism*
  • Real-Time Polymerase Chain Reaction


  • DNA Primers
  • Fatty Acid-Binding Proteins
  • Fatty Acids
  • Interleukin-6
  • PPAR alpha