Vida, MargaritaGavito, Ana LuisaPavón, Francisco JavierBautista, DoloresSerrano, AntoniaSuarez, JuanArrabal, SergioDecara, JuanRomero-Cuevas, MiguelRodríguez de Fonseca, FernandoBaixeras, Elena2016-06-282016-06-282015-07-01Vida M, Gavito AL, Pavón FJ, Bautista D, Serrano A, Suarez J, et al. Chronic administration of recombinant IL-6 upregulates lipogenic enzyme expression and aggravates high-fat-diet-induced steatosis in IL-6-deficient mice. Dis Model Mech. 2015 ; 8(7):721-311754-8403http://hdl.handle.net/10668/2233Journal Article; Research Support, Non-U.S. Gov't;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.enLiverLipogenesisSteatosisInterleukin-6Modelos de enfermedad en animalesÁcido graso sintasa tipo ICélulas Hep G2Interleucina-6LipogénesisHígadoRatonesRatones consanguíneos C57BLRatones noqueadosEsteatosis hepática no alcohólicaFosforilaciónProteínas recombinantesFactor de transcripción STAT3Estearoil-CoA desaturasaSupresor de proteínas señalizadoras de citocinasCitoquinesisCarnitina O-palmitoiltransferasaAcetil-CoA carboxilasaAlimentación rica en grasaMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Ligases::Carbon-Carbon Ligases::Acetyl-CoA CarboxylaseMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Acyltransferases::Carnitine Acyltransferases::Carnitine O-PalmitoyltransferaseMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Cycle::Cell Division::CytokinesisMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet::Diet, High-FatMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Animal::Disease Models, AnimalMedical Subject Headings::Anatomy::Cells::Epithelial Cells::Hepatocytes::Hep G2 CellsMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines::Interleukins::Interleukin-6Medical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::Lipid Metabolism::LipogenesisMedical Subject Headings::Anatomy::Digestive System::LiverMedical Subject Headings::Check Tags::MaleMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::MiceMedical Subject Headings::Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Laboratory::Animals, Inbred Strains::Mice, Inbred Strains::Mice, Inbred C57BLMedical Subject Headings::Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Genetically Modified::Mice, Transgenic::Mice, KnockoutMedical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::PhosphorylationMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Recombinant ProteinsMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Transcription Factors::STAT Transcription Factors::STAT3 Transcription FactorMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Oxidoreductases::Oxygenases::Mixed Function Oxygenases::Fatty Acid Desaturases::Stearoyl-CoA DesaturaseMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Intracellular Signaling Peptides and Proteins::Adaptor Proteins, Signal Transducing::Suppressor of Cytokine Signaling ProteinsMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Serine-Threonine Kinases::AMP-Activated Protein KinasesMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Multifunctional Enzymes::Fatty Acid Synthase, Type IMedical Subject Headings::Diseases::Digestive System Diseases::Liver Diseases::Fatty Liver::Non-alcoholic Fatty Liver Diseaseresearch article26035386open access10.1242/dmm.0191661754-8411PMC4486858