Ketogenic diet uncovers differential metabolic plasticity of brain cells.
Tim DükingLena SpiethStefan A BerghoffLars PiepkornAnnika M SchmidkeMiso MitkovskiNirmal R KannaiyanLeon HosangPatricia ScholzAli H ShaibLennart V SchneiderDörte HesseTorben RuhwedelTing SunLisa LinhoffAndrea TrevisiolSusanne KöhlerAdrian Marti PastorThomas MisgeldMichael SeredaImam HassounaMoritz J RossnerFrancesca OdoardiTill IschebeckLivia de HozJohannes HirrlingerOlaf JahnGesine SaherPublished in: Science advances (2022)
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.
Keyphrases
- single cell
- cerebral ischemia
- white matter
- physical activity
- resting state
- induced apoptosis
- cell therapy
- cell cycle arrest
- functional connectivity
- oxidative stress
- weight loss
- type diabetes
- stem cells
- cell death
- subarachnoid hemorrhage
- metabolic syndrome
- multiple sclerosis
- spinal cord injury
- endoplasmic reticulum stress
- young adults
- lipopolysaccharide induced
- childhood cancer