Ketogenic diet uncovers differential metabolic plasticity of brain cells

Düking, Tim; Spieth, Lena; Berghoff, Stefan A.; Piepkorn, Lars; Schmidke, Annika M.; Mitkovski, Miso; Kannaiyan, Nirmal; Hosang, Leon; Scholz, Patricia; Shaib, Ali H.; Schneider, Lennart V.; Hesse, Dörte; Ruhwedel, Torben; Sun, Ting; Linhoff, Lisa; Trevisiol, Andrea; Köhler, Susanne; Pastor, Adrian Marti; Misgeld, Thomas; Sereda, Michael; Hassouna, Imam; Rossner, Moritz J.; Odoardi, Francesca; Ischebeck, Till; de Hoz, Livia; Hirrlinger, Johannes; Jahn, Olaf; Saher, Gesine

doi:10.1126/sciadv.abo7639

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Ketogenic diet uncovers differential metabolic plasticity of brain cells

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Düking, Tim
Department of Neurogenetics, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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Spieth, Lena
Department of Neurogenetics, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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Berghoff, Stefan A.
Department of Neurogenetics, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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Piepkorn, Lars
Department of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

Schmidke, Annika M.
Department of Neurogenetics, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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Mitkovski, Miso
Facility for Light Microscopy, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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Shaib, Ali H.
Department of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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Schneider, Lennart V.
Department of Neurogenetics, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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Hesse, Dörte
Department of Neurogenetics, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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Ruhwedel, Torben
Department of Neurogenetics, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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Sun, Ting
Department of Neurogenetics, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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Trevisiol, Andrea
Department of Neurogenetics, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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Hassouna, Imam
Department of Neurogenetics, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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de Hoz, Livia
Department of Neurogenetics, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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Hirrlinger, Johannes
Department of Neurogenetics, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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Jahn, Olaf
Department of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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Saher, Gesine
Department of Neurogenetics, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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Citation

Düking, T., Spieth, L., Berghoff, S. A., Piepkorn, L., Schmidke, A. M., Mitkovski, M., et al. (2022). Ketogenic diet uncovers differential metabolic plasticity of brain cells. Science Advances, 8(37): eabo7639. doi:10.1126/sciadv.abo7639.

Cite as: https://hdl.handle.net/21.11116/0000-000B-3BC4-6

Abstract

To maintain homeostasis, the body, including the brain, reprograms its metabolism in response to altered nutrition or disease. However, the consequences of these challenges for the energy metabolism of the different brain cell types remain unknown. Here, we generated a proteome atlas of the major central nervous system (CNS) cell types from young and adult mice, after feeding the therapeutically relevant low-carbohydrate, high-fat ketogenic diet (KD) and during neuroinflammation. Under steady-state conditions, CNS cell types prefer distinct modes of energy metabolism. Unexpectedly, the comparison with KD revealed distinct cell type–specific strategies to manage the altered availability of energy metabolites. Astrocytes and neurons but not oligodendrocytes demonstrated metabolic plasticity. Moreover, inflammatory demyelinating disease changed the neuronal metabolic signature in a similar direction as KD. Together, these findings highlight the importance of the metabolic cross-talk between CNS cells and between the periphery and the brain to manage altered nutrition and neurological disease.