Influence of a ketogenic diet on glial metabolism in vivo - Oligodendrocytes

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 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. Surprisingly, 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. Unexpectedly, inflammatory demyelinating disease changed the neuronal metabolic signature in a similar direction as KD. Together, these findings highlight the importance of the metabolic crosstalk between CNS cells and between the periphery and the brain to manage altered nutrition and neurological disease. Overall design: Mice are reared on ketogenic diet (KD) until P42, morphological and metabolic changes are investigated globally with transcriptomic analysis. Oligodendrocytes were purified by MACS.