title: Visfatin induces oxidative stress in differentiated C2C12 myotubes in an Akt- and MAPK-independent, NFkB-dependent manner.
abstract: Adipose tissue is an important endocrine and metabolic tissue that is actively involved in cross-talk with peripheral organs such as skeletal muscle. It is likely that adipose-derived factors may underlie the development of insulin resistance in muscle. Thus, the cross-talk between adipose and muscle may be important for the propagation of obesity-related diseases. Visfatin (Pre-B-cell colony-enhancing factor 1 homolog/Nampt) is a recently discovered adipokine with pleiotropic functions. The aim of this study was to examine the effect of visfatin on cellular stress responses and signalling pathways in skeletal muscle. Visfatin treatment of differentiated C2C12 myotubes generated reactive oxygen species (ROS) comprising both superoxide and hydrogen peroxide that was dependent on de novo transcription and translation. In differentiated C2C12 myoblasts, visfatin had no effects on insulin-stimulated Akt phosphorylation nor on activation of the Akt signalling pathway. Additionally, visfatin-induced oxidative stress occurred independent of activation of the stress-activated protein kinases (MAPKs) ERK and p38. In contrast, phosphorylation of NFkB was associated with visfatin-mediated generation of ROS and blockade of this pathway via selective IKK inhibition led to a partial reduction in oxidative stress. Furthermore, the generation of ROS following visfatin treatment was highly dependent on both de novo transcription and translation. Taken together, these findings provide novel insights for the unique pathophysiological role of visfatin in skeletal muscle.
authors.affiliation: Unilever Discover, Colworth Science Park, Sharnbrook, Bedfordshire, MK44 1LQ, UK.
authors.forename: Radu C
authors.initials: RC
authors.lastname: Oita
authors.forename: Dudley
authors.initials: D
authors.lastname: Ferdinando
authors.forename: Steve
authors.initials: S
authors.lastname: Wilson
authors.forename: Christopher
authors.initials: C
authors.lastname: Bunce
authors.forename: Dawn J
authors.initials: DJ
authors.lastname: Mazzatti
mesh_terms: D000818:Animals; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D054409:Nicotinamide Phosphoribosyltransferase / Q000494:pharmacology / Q000502:physiology*; D018384:Oxidative Stress; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D054409:Nicotinamide Phosphoribosyltransferase; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases