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

Authors

  • Margarita Vida,

    1. Laboratorio de Medicina Regenerativa, IBIMA, Málaga, Spain
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  • Antonia Serrano,

    1. Laboratorio de Medicina Regenerativa, IBIMA, Málaga, Spain
    2. Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III (ISCIII), Spain
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  • Miguel Romero-Cuevas,

    1. Laboratorio de Medicina Regenerativa, IBIMA, Málaga, Spain
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  • Francisco J. Pavón,

    1. Laboratorio de Medicina Regenerativa, IBIMA, Málaga, Spain
    2. Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III (ISCIII), Spain
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  • Águeda González-Rodriguez,

    1. Instituto de Investigaciones Biomédicas Alberto Sols (CSIC/UAM), Madrid, Spain
    2. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Spain
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  • Ana L. Gavito,

    1. Laboratorio de Medicina Regenerativa, IBIMA, Málaga, Spain
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  • Antonio L. Cuesta,

    1. Laboratorio de Medicina Regenerativa, IBIMA, Málaga, Spain
    2. UGC-Medicina Interna, Hospital Regional Universitario Carlos Haya, Málaga, Spain
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  • Ángela M. Valverde,

    1. Instituto de Investigaciones Biomédicas Alberto Sols (CSIC/UAM), Madrid, Spain
    2. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Spain
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  • Fernando Rodríguez de Fonseca,

    1. Laboratorio de Medicina Regenerativa, IBIMA, Málaga, Spain
    2. Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III (ISCIII), Spain
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  • Elena Baixeras

    Corresponding author
    1. UGC-Medicina Interna, Hospital Regional Universitario Carlos Haya, Málaga, Spain
    • Laboratorio de Medicina Regenerativa, IBIMA, Málaga, Spain
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Correspondence

Dr. Elena Baixeras, Laboratorio de Medicina Regenerativa, Hospital Carlos Haya, IBIMA, Avenida Carlos Haya 82, Malaga 29010, Spain

Tel: +34 951291446

Fax: +34 952614012

e-mail: elena.baixeras@fundacionimabis.org

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.

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.

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