title: IL-6 cooperates with peroxisome proliferator-activated receptor-α-ligands to induce liver fatty acid binding protein (LFABP) up-regulation.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Laboratorio de Medicina Regenerativa, IBIMA, Málaga, Spain.
authors.forename: Margarita
authors.initials: M
authors.lastname: Vida
authors.forename: Antonia
authors.initials: A
authors.lastname: Serrano
authors.forename: Miguel
authors.initials: M
authors.lastname: Romero-Cuevas
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Pavón
authors.forename: Agueda
authors.initials: A
authors.lastname: González-Rodriguez
authors.forename: Ana L
authors.initials: AL
authors.lastname: Gavito
authors.forename: Antonio L
authors.initials: AL
authors.lastname: Cuesta
authors.forename: Angela M
authors.initials: AM
authors.lastname: Valverde
authors.forename: Fernando
authors.initials: F
authors.lastname: Rodríguez de Fonseca
authors.forename: Elena
authors.initials: E
authors.lastname: Baixeras
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D017931:DNA Primers / Q000235:genetics; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D047493:PPAR alpha / Q000187:drug effects / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D015850:Interleukin-6; D047493:PPAR alpha
keywords: GW-6471; LFABP; PPARα; WY-14,643; hepatocyte; interleukin 6; oleoylethanolamide (OEA)