Exploring Valine Metabolism in Astrocytic and Liver Cells: Lesson from Clinical Observation in TBI Patients for Nutritional Intervention

Sonnay, Sarah; Christinat, Nicolas; Thevenet, Jonathan; Wiederkehr, Andreas; Chakrabarti, Anirikh; Masoodi, Mojgan (2020). Exploring Valine Metabolism in Astrocytic and Liver Cells: Lesson from Clinical Observation in TBI Patients for Nutritional Intervention. Biomedicines, 8(11), p. 487. MDPI 10.3390/biomedicines8110487

[img]
Preview
Text
biomedicines-08-00487-v2.pdf - Published Version
Available under License Creative Commons: Attribution (CC-BY).

Download (887kB) | Preview

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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry

UniBE Contributor:

Masoodi, Mojgan

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2227-9059

Publisher:

MDPI

Language:

English

Submitter:

Karin Balmer

Date Deposited:

09 Dec 2020 17:46

Last Modified:

13 Dec 2020 02:51

Publisher DOI:

10.3390/biomedicines8110487

BORIS DOI:

10.7892/boris.148322

URI:

https://boris.unibe.ch/id/eprint/148322

Actions (login required)

Edit item Edit item
Provide Feedback