Exploring Valine Metabolism in Astrocytic and Liver Cells: Lesson from Clinical Observation in TBI Patients for Nutritional Intervention.
Sarah SonnayNicolas ChristinatJonathan ThevenetAndreas WiederkehrAnirikh ChakrabartiMojgan MasoodiPublished in: Biomedicines (2020)
The utilization of alternative energy substrates to glucose could be beneficial in traumatic brain injury (TBI). Recent clinical data obtained in TBI patients reported valine, β-hydroxyisobutyrate (ibHB) and 2-ketoisovaleric acid (2-KIV) as three of the main predictors of TBI outcome. In particular, higher levels of ibHB, 2-KIV, and valine in cerebral microdialysis (CMD) were associated with better clinical outcome. In this study, we investigate the correlations between circulating and CMD levels of these metabolites. We hypothesized that the liver can metabolize valine and provide a significant amount of intermediate metabolites, which can be further metabolized in the brain. We aimed to assess the metabolism of valine in human-induced pluripotent stem cell (iPSC)-derived astrocytes and HepG2 cells using 13C-labeled substrate to investigate potential avenues for increasing the levels of downstream metabolites of valine via valine supplementation. We observed that 94 ± 12% and 84 ± 16% of ibHB, and 94 ± 12% and 87 ± 15% of 2-KIV, in the medium of HepG2 cells and in iPSC-derived astrocytes, respectively, came directly from valine. Overall, these findings suggest that both ibHB and 2-KIV are produced from valine to a large extent in both cell types, which could be of interest in the design of optimal nutritional interventions aiming at stimulating valine metabolism.
Keyphrases
- traumatic brain injury
- stem cells
- end stage renal disease
- newly diagnosed
- ejection fraction
- severe traumatic brain injury
- chronic kidney disease
- randomized controlled trial
- prognostic factors
- endothelial cells
- machine learning
- mild traumatic brain injury
- risk assessment
- type diabetes
- blood pressure
- adipose tissue
- mesenchymal stem cells
- physical activity
- multiple sclerosis
- cell therapy
- climate change
- subarachnoid hemorrhage
- signaling pathway
- functional connectivity
- cell cycle arrest
- cell death
- human health
- resting state
- pet ct
- patient reported