Abstract
Background: Adiponectin (Adn), released by adipocytes and other cell types such as skeletal muscle, has insulin-sensitizing and anti-inflammatory properties. Sphingosine 1-phosphate (S1P) is reported to act as effector of diverse biological actions of Adn in different tissues. S1P is a bioactive sphingolipid synthesized by the phosphorylation of sphingosine catalyzed by sphingosine kinase (SK) 1 and 2. Consolidated findings support the key role of S1P in the biology of skeletal muscle. Methods and Results: Here we provide experimental evidence that S1P signalling is modulated by globular Adn treatment being able to increase the phosphorylation of SK1/2 as well as the mRNA expression levels of S1P4 in C2C12 myotubes. These findings were confirmed by LC-MS/MS that showed an increase of S1P levels after Adn treatment. Notably, the involvement of S1P axis in Adn action was highlighted since, when SK1 and 2 were inhibited by PF543 and ABC294640 inhibitors, respectively, not only the electrophysiological changes but also the increase of oxygen consumption and of aminoacid levels induced by the hormone, were significantly inhibited. Conclusion: Altogether, these findings show that S1P biosynthesis is necessary for the electrophysiological properties and oxidative metabolism of Adn in skeletal muscle cells.
Highlights
Skeletal muscle plays crucial functions in human metabolism and homeostasis, beyond the known contractile properties and the mechanical and structural functions of the organ
Treatment with globular Adn significantly increased the expression of S1P4 while the mRNA content of the other S1P receptors (S1PR) or the specific Sphingosine 1-phosphate (S1P) transporter spinster homolog2 (Spns2) (Figure 1a, lower panel) were unaffected by the treatment
Skeletal muscle is necessary for many fundamental biological processes in the human body such as movement, posture and energy homeostasis
Summary
Skeletal muscle plays crucial functions in human metabolism and homeostasis, beyond the known contractile properties and the mechanical and structural functions of the organ. Methods and Results: Here we provide experimental evidence that S1P signalling is modulated by globular Adn treatment being able to increase the phosphorylation of SK1/2 as well as the mRNA expression levels of S1P4 in C2C12 myotubes. These findings were confirmed by LC-MS/MS that showed an increase of S1P levels after Adn treatment. The involvement of S1P axis in Adn action was highlighted since, when SK1 and 2 were inhibited by PF543 and ABC294640 inhibitors, respectively, the electrophysiological changes and the increase of oxygen consumption and of aminoacid levels induced by the hormone, were significantly inhibited. Conclusion: Altogether, these findings show that S1P biosynthesis is necessary for the electrophysiological properties and oxidative metabolism of Adn in skeletal muscle cells
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