S1P Signalling Axis Is Necessary for Adiponectin-Directed Regulation of Electrophysiological Properties and Oxidative Metabolism in C2C12 Myotubes
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 sph...
| Main Authors: | , , , , , , , , , , , , , |
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MDPI AG
2022-02-01
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| Online Access: | https://www.mdpi.com/2073-4409/11/4/713 |
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| author | Caterina Bernacchioni Roberta Squecco Tania Gamberi Veronica Ghini Fabian Schumacher Michele Mannelli Rachele Garella Eglantina Idrizaj Francesca Cencetti Elisa Puliti Paola Bruni Paola Turano Tania Fiaschi Chiara Donati |
| author_facet | Caterina Bernacchioni Roberta Squecco Tania Gamberi Veronica Ghini Fabian Schumacher Michele Mannelli Rachele Garella Eglantina Idrizaj Francesca Cencetti Elisa Puliti Paola Bruni Paola Turano Tania Fiaschi Chiara Donati |
| author_sort | Caterina Bernacchioni |
| collection | DOAJ |
| description | 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 S1P<sub>4</sub> 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. |
| first_indexed | 2024-03-09T22:19:56Z |
| format | Article |
| id | doaj.art-2a3a1af638c04939b38607600df84873 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T22:19:56Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-2a3a1af638c04939b38607600df848732023-11-23T19:15:50ZengMDPI AGCells2073-44092022-02-0111471310.3390/cells11040713S1P Signalling Axis Is Necessary for Adiponectin-Directed Regulation of Electrophysiological Properties and Oxidative Metabolism in C2C12 MyotubesCaterina Bernacchioni0Roberta Squecco1Tania Gamberi2Veronica Ghini3Fabian Schumacher4Michele Mannelli5Rachele Garella6Eglantina Idrizaj7Francesca Cencetti8Elisa Puliti9Paola Bruni10Paola Turano11Tania Fiaschi12Chiara Donati13Department of Experimental and Clinical Biomedical Sciences “M. Serio”, University of Florence, 50134 Florence, ItalySection of Physiological Sciences, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, ItalyDepartment of Experimental and Clinical Biomedical Sciences “M. Serio”, University of Florence, 50134 Florence, ItalyMagnetic Resonance Center (CERM), University of Florence, 50019 Florence, ItalyInstitute of Pharmacy, Freie Universität Berlin, Königin-Luise-Str. 2+4, 14195 Berlin, GermanyDepartment of Experimental and Clinical Biomedical Sciences “M. Serio”, University of Florence, 50134 Florence, ItalySection of Physiological Sciences, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, ItalySection of Physiological Sciences, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, ItalyDepartment of Experimental and Clinical Biomedical Sciences “M. Serio”, University of Florence, 50134 Florence, ItalyDepartment of Experimental and Clinical Biomedical Sciences “M. Serio”, University of Florence, 50134 Florence, ItalyDepartment of Experimental and Clinical Biomedical Sciences “M. Serio”, University of Florence, 50134 Florence, ItalyMagnetic Resonance Center (CERM), University of Florence, 50019 Florence, ItalyDepartment of Experimental and Clinical Biomedical Sciences “M. Serio”, University of Florence, 50134 Florence, ItalyDepartment of Experimental and Clinical Biomedical Sciences “M. Serio”, University of Florence, 50134 Florence, ItalyBackground: 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 S1P<sub>4</sub> 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.https://www.mdpi.com/2073-4409/11/4/713adiponectinsphingosine kinaseskeletal musclesphingosine 1-phosphateelectrophysiological propertiesNMR metabolomics |
| spellingShingle | Caterina Bernacchioni Roberta Squecco Tania Gamberi Veronica Ghini Fabian Schumacher Michele Mannelli Rachele Garella Eglantina Idrizaj Francesca Cencetti Elisa Puliti Paola Bruni Paola Turano Tania Fiaschi Chiara Donati S1P Signalling Axis Is Necessary for Adiponectin-Directed Regulation of Electrophysiological Properties and Oxidative Metabolism in C2C12 Myotubes Cells adiponectin sphingosine kinase skeletal muscle sphingosine 1-phosphate electrophysiological properties NMR metabolomics |
| title | S1P Signalling Axis Is Necessary for Adiponectin-Directed Regulation of Electrophysiological Properties and Oxidative Metabolism in C2C12 Myotubes |
| title_full | S1P Signalling Axis Is Necessary for Adiponectin-Directed Regulation of Electrophysiological Properties and Oxidative Metabolism in C2C12 Myotubes |
| title_fullStr | S1P Signalling Axis Is Necessary for Adiponectin-Directed Regulation of Electrophysiological Properties and Oxidative Metabolism in C2C12 Myotubes |
| title_full_unstemmed | S1P Signalling Axis Is Necessary for Adiponectin-Directed Regulation of Electrophysiological Properties and Oxidative Metabolism in C2C12 Myotubes |
| title_short | S1P Signalling Axis Is Necessary for Adiponectin-Directed Regulation of Electrophysiological Properties and Oxidative Metabolism in C2C12 Myotubes |
| title_sort | s1p signalling axis is necessary for adiponectin directed regulation of electrophysiological properties and oxidative metabolism in c2c12 myotubes |
| topic | adiponectin sphingosine kinase skeletal muscle sphingosine 1-phosphate electrophysiological properties NMR metabolomics |
| url | https://www.mdpi.com/2073-4409/11/4/713 |
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