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IL ‐6 cooperates with peroxisome proliferator‐activated receptor‐α‐ligands to induce liver fatty acid binding protein ( LFABP ) up‐regulation
Author(s) -
Vida Margarita,
Serrano Antonia,
RomeroCuevas Miguel,
Pavón Francisco J.,
GonzálezRodriguez Águeda,
Gavito Ana L.,
Cuesta Antonio L.,
Valverde Ángela M.,
Rodríguez de Fonseca Fernando,
Baixeras Elena
Publication year - 2013
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.12156
Subject(s) - peroxisome , chemistry , peroxisome proliferator activated receptor alpha , peroxisome proliferator activated receptor , receptor , biochemistry , peroxisome proliferator activated receptor gamma , peroxisome proliferator , transcription factor , nuclear receptor , gene
Abstract Background LFABP plays a critical role in the uptake and intracellular transport of fatty acids ( FA ) and other peroxisome proliferator‐activated receptor alpha ( PPAR α) ligands. PPAR α activation by PPAR α 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 PPAR α. The maximum increase in LFABP expression occurs when the stimulation with IL ‐6 and PPAR α‐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.