4.8 Article

Ketogenic diet uncovers differential metabolic plasticity of brain cells

Journal

SCIENCE ADVANCES
Volume 8, Issue 37, Pages -

Publisher

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abo7639

Keywords

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Funding

  1. German Research Foundation [Hi1414/6-1, Hi1414/7-1, SPP1757, SA2114/2, OD87/1-1, OD87/3-1, TRR274/1, 408885537, 390857198, RO 4076/3-2, IS273/10-1]
  2. Alzheimer Forschung Initiative [19070]
  3. Wilhelm-Sander Stiftung [2019.138.1]
  4. Klaus Faber Stiftung
  5. Studienstiftung des deutschen Volkes

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This study provides insights into the energy metabolism of different brain cell types in response to altered nutrition and neurological disease, highlighting the importance of metabolic cross-talk between CNS cells and between the periphery and the brain.
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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