Dokument: Intracellular Sphingosine‐1‐Phosphate Induces Lipolysis Through Direct Activation of Protein Kinase C Zeta
| Titel: | Intracellular Sphingosine‐1‐Phosphate Induces Lipolysis Through Direct Activation of Protein Kinase C Zeta | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=69628 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20250513-112620-1 | |||||||
| Kollektion: | Publikationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Texte » Artikel, Aufsatz | |||||||
| Medientyp: | Text | |||||||
| Autoren: | Weske, Sarah [Autor] Nowak, Melissa K. [Autor] Zaufel, Alex [Autor] Esser, Lea [Autor] Peter, Christoph [Autor] Walz, Lisa [Autor] Kühn, Helena [Autor] Wolde, Tsyon [Autor] Hoppe, Julia [Autor] Schröder, Nathalie H. [Autor] | |||||||
| Dateien: |
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| Stichwörter: | lipolysis, adipocytes, S1P lyase, lipidomics, sphingosine-1-phosphate (S1P), S1P receptors | |||||||
| Beschreibung: | Dysregulated sphingosine-1-phosphate (S1P) signaling has been associated with obesity, insulin resistance, and type II diabetes. As metabolic disorders are intricately interrelated, studies on S1P effects explicitly on lipolysis have been scarce, particularly as S1P has also effects on adipogenesis, with studies implicating extracellular and intracellular mechanisms. Here, we have concentrated on the latter, as 10–50 μM S1P potently increased lipolysis in differentiated 3T3-L1 adipocytes, whereas S1P concentrations sufficient to activate S1P receptors (S1PRs; 0.1–1 μM) or S1PR agonists had no effect. Neither was ceramide increased by S1P, nor was S1P-mediated lipolysis affected by the ceramide synthase inhibitor Fumonisin B1. In contrast, inhibition of protein kinase C zeta (PKC zeta) completely abrogated S1P-mediated lipolysis. S1P also induced Thr410 phosphorylation of PKC zeta in 3T3-L1 adipocytes and activated recombinant PKC zeta in kinase assays. S1P-mediated lipolysis was dependent on hormone-sensitive lipase (HSL) and relied mechanistically on PKC zeta activation of MAPK to phosphorylate HSL at Ser660. Inhibition of S1P degradation by blocking the S1P lyase through VD-78 also increased lipolysis in 3T3-L1 cells and primary adipocytes. S1P lyase inhibition by 4-Deoxypyridoxine (DOP) in mice rendered obese by a 10-week high-fat diet (HFD) for an additional 6 weeks, concomitantly with the HFD, reduced white gonadal adipose tissue (gWAT) mass and diminished adipocyte size in gWAT and inguinal WAT, and increased free fatty acid in plasma and gWAT. PKC zeta phosphorylation and activity, as well as HSL Ser660 phosphorylation, were increased in gWAT of DOP-treated mice. This study assigns lipolysis as the first physiological function of PKC zeta activation by S1P and identifies an exclusive adipocyte-specific aspect of S1P function in obesity. | |||||||
| Rechtliche Vermerke: | Originalveröffentlichung:
Weske, S., Nowak, M. K., Zaufel, A., Esser, L. M., Peter, C., Walz, L., Kühn, H., Wolde, T., Hoppe, J., Schröder, N. H., Buschmann, T., Wollnitzke, P., & Levkau, B. (2025). Intracellular Sphingosine‐1‐Phosphate Induces Lipolysis Through Direct Activation of Protein Kinase C Zeta. The FASEB Journal / Federation of American Societies for Experimental Biology, 39(7), Article e70528. https://doi.org/10.1096/fj.202403272r | |||||||
| Lizenz: |  Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz | |||||||
| Fachbereich / Einrichtung: | Medizinische Fakultät | |||||||
| Dokument erstellt am: | 13.05.2025 | |||||||
| Dateien geändert am: | 13.05.2025 |
