%0 Journal Article
%A Vida, Margarita
%A Gavito, Ana Luisa
%A Pavón, Francisco Javier
%A Bautista, Dolores
%A Serrano, Antonia
%A Suarez, Juan
%A Arrabal, Sergio
%A Decara, Juan
%A Romero-Cuevas, Miguel
%A Rodríguez de Fonseca, Fernando
%A Baixeras, Elena
%T Chronic administration of recombinant IL-6 upregulates lipogenic enzyme expression and aggravates high-fat-diet-induced steatosis in IL-6-deficient mice.
%D 2015
%@ 1754-8403
%U http://hdl.handle.net/10668/2233
%X Interleukin-6 (IL-6) has emerged as an important mediator of fatty acid metabolism with paradoxical effects in the liver. Administration of IL-6 has been reported to confer protection against steatosis, but plasma and tissue IL-6 concentrations are elevated in chronic liver diseases, including fatty liver diseases associated with obesity and alcoholic ingestion. In this study, we further investigated the role of IL-6 on steatosis induced through a high-fat diet (HFD) in wild-type (WT) and IL-6-deficient (IL-6(-/-)) mice. Additionally, HFD-fed IL-6(-/-) mice were also chronically treated with recombinant IL-6 (rIL-6). Obesity in WT mice fed a HFD associated with elevated serum IL-6 levels, fatty liver, upregulation of carnitine palmitoyltransferase 1 (CPT1) and signal transducer and activator of transcription-3 (STAT3), increased AMP kinase phosphorylation (p-AMPK), and downregulation of the hepatic lipogenic enzymes fatty acid synthase (FAS) and stearoyl-CoA desaturase 1 (SCD1). The HFD-fed IL-6(-/-) mice showed severe steatosis, no changes in CPT1 levels or AMPK activity, no increase in STAT3 amounts, inactivated STAT3, and marked downregulation of the expression of acetyl-CoA carboxylase (ACCα/β), FAS and SCD1. The IL-6 chronic replacement in HFD-fed IL-6 -/-: mice restored hepatic STAT3 and AMPK activation but also increased the expression of the lipogenic enzymes ACCα/β, FAS and SCD1. Furthermore, rIL-6 administration was associated with aggravated steatosis and elevated fat content in the liver. We conclude that, in the context of HFD-induced obesity, the administration of rIL-6 might contribute to the aggravation of fatty liver disease through increasing lipogenesis.
%K Liver
%K Lipogenesis
%K Steatosis
%K Interleukin-6
%K Modelos de enfermedad en animales
%K Ácido graso sintasa tipo I
%K Células Hep G2
%K Interleucina-6
%K Lipogénesis
%K Hígado
%K Ratones
%K Ratones consanguíneos C57BL
%K Ratones noqueados
%K Esteatosis hepática no alcohólica
%K Fosforilación
%K Proteínas recombinantes
%K Factor de transcripción STAT3
%K Estearoil-CoA desaturasa
%K Supresor de proteínas señalizadoras de citocinas
%K Citoquinesis
%K Carnitina O-palmitoiltransferasa
%K Acetil-CoA carboxilasa
%K Alimentación rica en grasa
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