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Type: Artigo
Title: The role of proliferator-activated receptor γ coactivator–1α in the fatty-acid–dependent transcriptional control of interleukin-10 in hepatic cells of rodents
Author: Morari, Joseane
Torsoni, Adrian S.
Anhê, Gabriel F.
Roman, Erika A.
Cintra, Dennys E.
Ward, Laura S.
Bordin, Silvana
Velloso, Lício A.
Abstract: Interleukin-10 (IL-10) is an endogenous factor that restrains hepatic insulin resistance in diet-induced steatosis. Reducing IL-10 expression increases proinflammatory activity in the steatotic liver and worsens insulin resistance. As the transcriptional coactivator proliferator-activated receptor γ coactivator–1 α (PGC-1 α) plays a central role in dysfunctional hepatocytic activity in diet-induced steatosis, we hypothesized that at least part of the action of PGC-1 α could be mediated by reducing the transcription of the IL-10 gene. Here, we used immunoblotting, real-time polymerase chain reaction, immunocytochemistry, and chromatin immunoprecipitation assay to investigate the role of PGC-1 α in the control of IL-10 expression in hepatic cells. First, we show that, in the intact steatotic liver, the expressions of IL-10 and PGC-1 α are increased. Inhibiting PGC-1 α expression by antisense oligonucleotide increases IL-10 expression and reduces the steatotic phenotype. In cultured hepatocytes, the treatment with saturated and unsaturated fatty acids increased IL-10 expression. This was accompanied by increased association of PGC-1 α with c-Maf and p50–nuclear factor (NF) κB, 2 transcription factors known to modulate IL-10 expression. In addition, after fatty acid treatment, PGC-1 α, c-Maf, and p50-NF κB migrate from the cytosol to the nuclei of hepatocytes and bind to the IL-10 promoter region. Inhibiting NF κB activation with salicylate reduces IL-10 expression and the association of PGC-1 α with p50-NF κB. Thus, PGC-1 α emerges as a potential transcriptional regulator of the inflammatory phenomenon taking place in the steatotic liver
Subject: Hepatócitos
Country: Estados Unidos
Editor: Elsevier
Rights: Fechado
Identifier DOI: 10.1016/j.metabol.2009.07.020
Date Issue: 2010
Appears in Collections:FCM - Artigos e Outros Documentos

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