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Visfatin induces oxidative stress in differentiated C2C12 myotubes in an Akt- and MAPK-independent, NFĸB-dependent manner

  • Muscle Physiology
  • Published:
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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 NFĸB 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.

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Acknowledgements

RCO is supported by the NUCSYS Marie Curie Research Training Network funded by the European Union (contract number: MRTN-CT-019496).

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Authors and Affiliations

  1. Unilever Discover, Colworth Science Park, Sharnbrook, Bedfordshire, MK44 1LQ, UK

    Radu C. Oita, Dudley Ferdinando, Steve Wilson & Dawn J. Mazzatti

  2. University of Birmingham, Birmingham, UK

    Radu C. Oita & Christopher Bunce

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  1. Radu C. Oita
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  2. Dudley Ferdinando
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Correspondence to Dawn J. Mazzatti.

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Oita, R.C., Ferdinando, D., Wilson, S. et al. Visfatin induces oxidative stress in differentiated C2C12 myotubes in an Akt- and MAPK-independent, NFĸB-dependent manner. Pflugers Arch - Eur J Physiol 459, 619–630 (2010). https://doi.org/10.1007/s00424-009-0752-1

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