Oligodendroglial fatty acid metabolism as a central nervous system energy reserve
Brain function requires a constant supply of glucose. However, the brain has no known energy stores, except for glycogen granules in astrocytes. In the present study, we report that continuous oligodendroglial lipid metabolism provides an energy reserve in white matter tracts. In the isolated optic nerve from young adult mice of both sexes, oligodendrocytes survive glucose deprivation better than astrocytes. Under low glucose, both axonal ATP levels and action potentials become dependent on fatty acid β-oxidation. Importantly, ongoing oligodendroglial lipid degradation feeds rapidly into white matter energy metabolism. Although not supporting high-frequency spiking, fatty acid β-oxidation in mitochondria and oligodendroglial peroxisomes protects axons from conduction blocks when glucose is limiting. Disruption of the glucose transporter GLUT1 expression in oligodendrocytes of adult mice perturbs myelin homeostasis in vivo and causes gradual demyelination without behavioral signs. This further suggests that the imbalance of myelin synthesis and degradation can underlie myelin thinning in aging and disease.
Authors
- Michelle‐Amirah Khalil
- Reyhane Ebrahimi (ORCID: https://orcid.org/0000-0003-4938-2639)
- Bruno Weber (ORCID: https://orcid.org/0000-0002-9089-0689)
- Celia M. Kassmann (ORCID: https://orcid.org/0000-0003-0993-9455)
- Jun Yup Lee (ORCID: https://orcid.org/0000-0002-3983-4024)
- Kathrin Kusch (ORCID: https://orcid.org/0000-0002-5079-502X)
- Myriam Baes (ORCID: https://orcid.org/0000-0002-2525-2269)
- Klaus‐Armin Nave (ORCID: https://orcid.org/0000-0001-8724-9666)
- Anthony S. Don (ORCID: https://orcid.org/0000-0003-1655-1184)
- Torben Ruhwedel (ORCID: https://orcid.org/0000-0002-9535-9395)
- Payam Dibaj (ORCID: https://orcid.org/0000-0003-1585-6330)
- Zoe J. Looser (ORCID: https://orcid.org/0000-0003-0741-0195)
- Aiman S. Saab (ORCID: https://orcid.org/0000-0003-3886-8369)
- Olaf Jahn (ORCID: https://orcid.org/0000-0002-3397-8924)
- Ebrahim Asadollahi (ORCID: https://orcid.org/0000-0003-4737-3587)
- Hannelore Ehrenreich (ORCID: https://orcid.org/0000-0001-8371-5711)
- Johannes Hirrlinger (ORCID: https://orcid.org/0000-0002-6327-0089)
- Karsten Hiller (ORCID: https://orcid.org/0000-0001-9322-5820)
- Andrea Ballabio (ORCID: https://orcid.org/0000-0003-1381-4604)
- Andrea Trevisiol (ORCID: https://orcid.org/0000-0002-7265-3639)
- Brian Popko (ORCID: https://orcid.org/0000-0001-9948-2553)
- Wiebke Möbius (ORCID: https://orcid.org/0000-0002-2902-7165)
- E. Dale Abel
Institutions
- Northwestern University (US)
- The University of Sydney (AU)
- Sunnybrook Health Science Centre (CA)
- University of California, Los Angeles (US)
- Baylor College of Medicine (US)
- University of Zurich (CH)
- Max Planck Institute for the Study of Religious and Ethnic Diversity (DE)
- Central Institute of Mental Health (DE)
- European Neuroscience Institute Göttingen (DE)
- Neurological Research Institute (US)
- Federico II University Hospital (IT)
- Max Planck Institute of Experimental Medicine (DE)
- Texas Children's Hospital (US)
- Telethon Institute Of Genetics And Medicine (IT)
- Max Planck Institute for Multidisciplinary Sciences (DE)
- University of Göttingen (DE)
- Leipzig University (DE)
- Technische Universität Braunschweig (DE)
- KU Leuven (BE)
Publication Details
- Journal
- Nature Neuroscience
- Published
- 2024-09-09
- DOI
- https://doi.org/10.1038/s41593-024-01749-6
- Citations
- 88
- Primary Topic
- Neuroinflammation and Neurodegeneration Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 21.78
Funders
- National Science Foundation
- Deutscher Akademischer Austauschdienst
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Max-Planck-Gesellschaft