IL-6 cooperates with peroxisome proliferator-activated receptor-α-ligands to induce liver fatty acid binding protein (LFABP) up-regulation
| Autor: | Fernando Rodríguez de Fonseca, Águeda González-Rodríguez, Ana Luisa Gavito, Ángela M. Valverde, Antonia Serrano, Francisco Javier Pavón, Margarita Vida, Elena Baixeras, Antonio Luis Cuesta, Miguel Romero-Cuevas |
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| Přispěvatelé: | Junta de Andalucía, Ministerio de Ciencia e Innovación (España), Instituto de Salud Carlos III, European Commission |
| Rok vydání: | 2013 |
| Předmět: |
medicine.medical_specialty
Blotting Western Peroxisome proliferator-activated receptor Interleukin 6 Biology WY-14 643 Fatty Acid-Binding Proteins Real-Time Polymerase Chain Reaction PPARα 03 medical and health sciences Mice LFABP 0302 clinical medicine Downregulation and upregulation Internal medicine Gene expression medicine Animals Humans PPAR alpha Hepatocyte GW-6471 Receptor 030304 developmental biology DNA Primers chemistry.chemical_classification 0303 health sciences Messenger RNA Analysis of Variance Hepatology Interleukin-6 Fatty Acids Hep G2 Cells Peroxisome 3. Good health Mice Inbred C57BL Endocrinology medicine.anatomical_structure chemistry Gene Expression Regulation Hepatocytes Oleoylethanolamide (OEA) 030217 neurology & neurosurgery Intracellular |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname Liver International; Vol 33 |
| Popis: | et al. [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. © 2013 John Wiley & Sons A/S. This work was supported by Grants PI061109, from the Spanish Institute of Health ‘Carlos III’; TCMR0019, PI0552, PI0236/08, PI0608/10 from the Andalusian Ministry of Health; SAF2012-33283, SAF2010-22113, SAF2010-20521 and CTS-6747/2010; from the Spanish Ministry of Science and Innovation and ‘Centro de Investigacion Biomédica en Red de Diabetes y Enfermedades Metabolicas Asociadas’ (CIBER-DEM), and CIBERobn EU-ERDF(CB06/03/1008). Grants from the European Union’s 7th Framework Programme (Health-F2-2008-223713, REPROBESITY). Elena Baixeras is a tenured investigator through the I3SNS Program of the ‘Andalusian Progreso y Salud Foundation’, Spain. |
| Databáze: | OpenAIRE |
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