Spexin Promotes the Proliferation and Differentiation of C2C12 Cells In Vitro-The Effect of Exercise on SPX and SPX Receptor Expression in Skeletal Muscle In Vivo

Genes (Basel). 2021 Dec 28;13(1):81. doi: 10.3390/genes13010081.


SPX (spexin) and its receptors GalR2 and GalR3 (galanin receptor subtype 2 and galanin receptor subtype 3) play an important role in the regulation of lipid and carbohydrate metabolism in human and animal fat tissue. However, little is still known about the role of this peptide in the metabolism of muscle. The aim of this study was to determine the impact of SPX on the metabolism, proliferation and differentiation of the skeletal muscle cell line C2C12. Moreover, we determined the effect of exercise on the SPX transduction pathway in mice skeletal muscle. We found that increased SPX, acting via GalR2 and GalR3 receptors, and ERK1/2 phosphorylation stimulated the proliferation of C2C12 cells (p < 0.01). We also noted that SPX stimulated the differentiation of C2C12 by increasing mRNA and protein levels of differentiation markers Myh, myogenin and MyoD (p < 0.01). SPX consequently promoted myoblast fusion into the myotubule (p < 0.01). Moreover, we found that, in the first stage (after 2 days) of myocyte differentiation, GalR2 and GalR3 were involved, whereas in the last stage (day six), the effect of SPX was mediated by the GalR3 isoform. We also noted that exercise stimulated SPX and GalR2 expression in mice skeletal muscle as well as an increase in SPX concentration in blood serum. These new insights may contribute to a better understanding of the role of SPX in the metabolism of skeletal muscle.

Keywords: C2C12 cells; differentiation; skeletal muscle; spexin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation*
  • Cell Proliferation*
  • Cells, Cultured
  • Gene Expression Regulation
  • In Vitro Techniques
  • Mice
  • Mice, Inbred C57BL
  • Muscle, Skeletal / cytology*
  • Muscle, Skeletal / metabolism
  • Peptide Hormones / genetics
  • Peptide Hormones / metabolism*
  • Phosphorylation
  • Physical Conditioning, Animal*
  • Receptor, Galanin, Type 1 / genetics
  • Receptor, Galanin, Type 1 / metabolism*
  • Receptor, Galanin, Type 2 / genetics
  • Receptor, Galanin, Type 2 / metabolism*


  • Peptide Hormones
  • Receptor, Galanin, Type 1
  • Receptor, Galanin, Type 2
  • Spx protein, mouse