title: Direct involvement of tumor necrosis factor-&alpha; in the regulation of glucose uptake in rainbow trout muscle cells.
abstract: The proinflammatory cytokine TNF-α is known to have a direct action on skeletal muscle in mammals. However, little is known regarding the potential effects of cytokines on nonimmune tissues, particularly in skeletal muscle, in fish. The aim of this study was to investigate the effects of recombinant trout TNF-α (rtTNF-α) on skeletal muscle carbohydrate metabolism in rainbow trout (Oncorhynchus mykiss). We used a primary cell culture of muscle cells from rainbow trout to show that rtTNF-α stimulates glucose uptake in myoblasts and myotubes at concentrations that do not affect the viability of the cells, requiring de novo protein synthesis as shown by the impairment of rtTNF-α-stimulated glucose uptake by cycloheximide. With the use of specific inhibitors, we show that rtTNF-α-stimulated glucose uptake is mediated by the p38MAPK, NF-κB, and JNK pathways. Additionally, we provide evidence that the stimulatory effects of rtTNF-α on glucose uptake in trout skeletal muscle cells may be caused, at least in part, by an increase in the amount of GLUT4 at the plasma membrane. Incubation of trout muscle cells with conditioned medium from LPS-stimulated trout macrophages, enriched in TNF-α, increased glucose uptake. Our results indicate that recombinant, as well as native trout TNF-α, directly stimulates glucose uptake in trout muscle cells and provide evidence, for the first time in nonmammalian vertebrates, for a potential regulatory role of TNF-α in skeletal muscle metabolism.
authors.affiliation: Departament de Fisiologia, Facultat de Biologia, Universitat de Barcelona, Institut de Biomedicina de la Universitat de Barcelona, Spain.
authors.forename: Yoryia
authors.initials: Y
authors.lastname: Vraskou
authors.forename: Nerea
authors.initials: N
authors.lastname: Roher
authors.forename: Monica
authors.initials: M
authors.lastname: Díaz
authors.forename: Costin N
authors.initials: CN
authors.lastname: Antonescu
authors.forename: Simon A
authors.initials: SA
authors.lastname: MacKenzie
authors.forename: Josep V
authors.initials: JV
authors.lastname: Planas
mesh_terms: D000818:Animals; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000378:metabolism; D003847:Deoxyglucose / Q000378:metabolism*; D029941:Fish Proteins / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D017686:Oncorhynchus mykiss / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D019899:Paracrine Communication; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D032496:Satellite Cells, Skeletal Muscle / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D029941:Fish Proteins; D051275:Glucose Transporter Type 4; D007328:Insulin; D008070:Lipopolysaccharides; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D011500:Protein Synthesis Inhibitors; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D003847:Deoxyglucose; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases