Ketogenic diet uncovers differential metabolic plasticity of brain cells

Sci Adv. 2022 Sep 16;8(37):eabo7639. doi: 10.1126/sciadv.abo7639.

Tim Düking ¹, Lena Spieth ¹, Stefan A Berghoff ¹, Lars Piepkorn ² ³, Annika M Schmidke ¹, Miso Mitkovski ⁴, Nirmal Kannaiyan ⁵, Leon Hosang ⁶, Patricia Scholz ⁷, Ali H Shaib ⁸ ⁹, Lennart V Schneider ¹, Dörte Hesse ¹ ², Torben Ruhwedel ¹ ¹⁰, Ting Sun ¹, Lisa Linhoff ¹¹ ¹², Andrea Trevisiol ¹, Susanne Köhler ¹³, Adrian Marti Pastor ¹⁴, Thomas Misgeld ¹⁴, Michael Sereda ¹¹ ¹², Imam Hassouna ¹, Moritz J Rossner ⁵, Francesca Odoardi ⁶, Till Ischebeck ⁷ ¹⁵, Livia de Hoz ¹ ¹⁶, Johannes Hirrlinger ¹ ¹³, Olaf Jahn ² ³, Gesine Saher ¹

Affiliations

1 Department of Neurogenetics, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
2 Neuroproteomics Group, Department of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
3 Translational Neuroproteomics Group, Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany.
4 City Campus Light Microscopy Facility, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
5 Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany.
6 Institute for Neuroimmunology and Multiple Sclerosis Research, University Medical Center Göttingen, Göttingen, Germany.
7 Department of Plant Biochemistry, Albrecht-von-Haller-Institute for Plant Sciences and Göttingen Center for Molecular Biosciences (GZMB), University of Göttingen, Göttingen, Germany.
8 Department of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
9 Institute for Neuro- and Sensory Physiology, Center for Biostructural Imaging of Neurodegeneration, University Medical Center Göttingen, Göttingen, Germany.
10 Electron Microscopy Core Unit, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
11 Department of Neurology, University Medical Center Göttingen, Göttingen, Germany.
12 Translational Neurogenetics, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
13 Carl-Ludwig-Institute for Physiology, Medical Faculty, University of Leipzig, Leipzig, Germany.
14 Institute of Neuronal Cell Biology, Technische Universität München, Cluster for Systems Neurology (SyNergy), German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
15 Institute of Plant Biology and Biotechnology (IBBP), Green Biotechnology, University of Münster, Münster, Germany.
16 Neurowissenschafliches Forschungszentrum, Charité - Universitätsmedizin Berlin, Berlin, Germany.

PMID: 36112685 DOI: 10.1126/sciadv.abo7639

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.

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