Rewiring of Glucose and Lipid Metabolism Induced by G Protein-Coupled Receptor 17 Silencing Enables the Transition of Oligodendrocyte Progenitors to Myelinating Cells
In the mature central nervous system (CNS), oligodendrocytes (OLs) provide support and insulation to axons thanks to the production of a myelin sheath. During their maturation to myelinating cells, OLs require energy and building blocks for lipids, which implies a great investment of energy fuels an...
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MDPI AG
2022-08-01
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| Online Access: | https://www.mdpi.com/2073-4409/11/15/2369 |
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| author | Davide Marangon Matteo Audano Silvia Pedretti Marta Fumagalli Nico Mitro Davide Lecca Donatella Caruso Maria P. Abbracchio |
| author_facet | Davide Marangon Matteo Audano Silvia Pedretti Marta Fumagalli Nico Mitro Davide Lecca Donatella Caruso Maria P. Abbracchio |
| author_sort | Davide Marangon |
| collection | DOAJ |
| description | In the mature central nervous system (CNS), oligodendrocytes (OLs) provide support and insulation to axons thanks to the production of a myelin sheath. During their maturation to myelinating cells, OLs require energy and building blocks for lipids, which implies a great investment of energy fuels and molecular sources of carbon. The oligodendroglial G protein-coupled receptor 17 (GPR17) has emerged as a key player in OL maturation; it reaches maximal expression in pre-OLs, but then it has to be internalized to allow terminal maturation. In this study, we aim at elucidating the role of physiological GPR17 downregulation in OL metabolism by applying transcriptomics, metabolomics and lipidomics on differentiating OLs. After GPR17 silencing, we found a significant increase in mature OL markers and alteration of several genes involved in glucose metabolism and lipid biosynthesis. We also observed an increased release of lactate, which is partially responsible for the maturation boost induced by GPR17 downregulation. Concomitantly, GPR17 depletion also changed the kinetics of specific myelin lipid classes. Globally, this study unveils a functional link between GPR17 expression, lactate release and myelin composition, and suggests that innovative interventions targeting GPR17 may help to foster endogenous myelination in demyelinating diseases. |
| first_indexed | 2024-03-09T05:31:34Z |
| format | Article |
| id | doaj.art-adad727a543741ae9641763f8e86dca7 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T05:31:34Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-adad727a543741ae9641763f8e86dca72023-12-03T12:32:24ZengMDPI AGCells2073-44092022-08-011115236910.3390/cells11152369Rewiring of Glucose and Lipid Metabolism Induced by G Protein-Coupled Receptor 17 Silencing Enables the Transition of Oligodendrocyte Progenitors to Myelinating CellsDavide Marangon0Matteo Audano1Silvia Pedretti2Marta Fumagalli3Nico Mitro4Davide Lecca5Donatella Caruso6Maria P. Abbracchio7Department of Pharmaceutical Sciences, Università degli Studi di Milano, 20133 Milan, ItalyDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, ItalyDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, ItalyDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, ItalyDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, ItalyDepartment of Pharmaceutical Sciences, Università degli Studi di Milano, 20133 Milan, ItalyDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, ItalyDepartment of Pharmaceutical Sciences, Università degli Studi di Milano, 20133 Milan, ItalyIn the mature central nervous system (CNS), oligodendrocytes (OLs) provide support and insulation to axons thanks to the production of a myelin sheath. During their maturation to myelinating cells, OLs require energy and building blocks for lipids, which implies a great investment of energy fuels and molecular sources of carbon. The oligodendroglial G protein-coupled receptor 17 (GPR17) has emerged as a key player in OL maturation; it reaches maximal expression in pre-OLs, but then it has to be internalized to allow terminal maturation. In this study, we aim at elucidating the role of physiological GPR17 downregulation in OL metabolism by applying transcriptomics, metabolomics and lipidomics on differentiating OLs. After GPR17 silencing, we found a significant increase in mature OL markers and alteration of several genes involved in glucose metabolism and lipid biosynthesis. We also observed an increased release of lactate, which is partially responsible for the maturation boost induced by GPR17 downregulation. Concomitantly, GPR17 depletion also changed the kinetics of specific myelin lipid classes. Globally, this study unveils a functional link between GPR17 expression, lactate release and myelin composition, and suggests that innovative interventions targeting GPR17 may help to foster endogenous myelination in demyelinating diseases.https://www.mdpi.com/2073-4409/11/15/2369oligodendrocyte progenitor celloligodendrocyteenergy metabolismglycolysislactatemyelin lipids |
| spellingShingle | Davide Marangon Matteo Audano Silvia Pedretti Marta Fumagalli Nico Mitro Davide Lecca Donatella Caruso Maria P. Abbracchio Rewiring of Glucose and Lipid Metabolism Induced by G Protein-Coupled Receptor 17 Silencing Enables the Transition of Oligodendrocyte Progenitors to Myelinating Cells Cells oligodendrocyte progenitor cell oligodendrocyte energy metabolism glycolysis lactate myelin lipids |
| title | Rewiring of Glucose and Lipid Metabolism Induced by G Protein-Coupled Receptor 17 Silencing Enables the Transition of Oligodendrocyte Progenitors to Myelinating Cells |
| title_full | Rewiring of Glucose and Lipid Metabolism Induced by G Protein-Coupled Receptor 17 Silencing Enables the Transition of Oligodendrocyte Progenitors to Myelinating Cells |
| title_fullStr | Rewiring of Glucose and Lipid Metabolism Induced by G Protein-Coupled Receptor 17 Silencing Enables the Transition of Oligodendrocyte Progenitors to Myelinating Cells |
| title_full_unstemmed | Rewiring of Glucose and Lipid Metabolism Induced by G Protein-Coupled Receptor 17 Silencing Enables the Transition of Oligodendrocyte Progenitors to Myelinating Cells |
| title_short | Rewiring of Glucose and Lipid Metabolism Induced by G Protein-Coupled Receptor 17 Silencing Enables the Transition of Oligodendrocyte Progenitors to Myelinating Cells |
| title_sort | rewiring of glucose and lipid metabolism induced by g protein coupled receptor 17 silencing enables the transition of oligodendrocyte progenitors to myelinating cells |
| topic | oligodendrocyte progenitor cell oligodendrocyte energy metabolism glycolysis lactate myelin lipids |
| url | https://www.mdpi.com/2073-4409/11/15/2369 |
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