BackgroundLFABP plays a critical role in the uptake and intracellular transport of fatty acids (FA) and other peroxisome proliferator-activated receptor alpha (PPAR) ligands. PPAR activation by PPAR 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. AimsTo 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 PPAR-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. ResultsIn hepatocyte cultures, IL-6 treatment stimulated a LFABP mRNA sustained expression. Combined treatment of IL-6 plus PPAR ligands further enhanced LFABP gene and protein expression. In contrast, pretreatment with the PPAR-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 8h after re-feeding was absent in mice lacking IL-6. ConclusionsIL-6 induces LFABP kinetics in hepatocytes and is partially dependent on PPAR. The maximum increase in LFABP expression occurs when the stimulation with IL-6 and PPAR-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.
