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[2,4-13 C2 ]-beta-Hydroxybutyrate metabolism in human brain
Jullie W Pan1, Robin A de Graaf, Kitt F Petersen
1Albert Einstein College of Medicine, Bronx, New York 10461, USA. jpan@aecom.yu.edu
Summary
Beta-hydroxybutyrate, a ketone body, enters and is rapidly metabolized in the human brain, primarily by neurons. This suggests the blood-brain barrier regulates ketone utilization in non-fasted adults.
Area of Science:
- Neuroscience
- Metabolic research
- Biochemistry
Background:
- Ketone bodies, such as beta-hydroxybutyrate, serve as alternative energy sources for the brain.
- Understanding ketone metabolism in the brain is crucial, especially in non-fasted states.
Purpose of the Study:
- To investigate the entry and metabolic fate of beta-hydroxybutyrate in the human brain.
- To quantify the utilization rate and contribution of beta-hydroxybutyrate to brain energy metabolism.
Main Methods:
- Utilized infusions of [2,4-13C2]-beta-hydroxybutyrate in healthy human subjects.
- Employed 1H-13C polarization transfer spectroscopy to track the 13C label in brain metabolites.
- Applied steady-state modeling to analyze 13C label distribution in amino acid pools.
Main Results:
- Detected 13C label from beta-hydroxybutyrate in brain amino acids (glutamate, glutamine, aspartate).
- Apparent tissue beta-hydroxybutyrate concentration reached 0.18 +/- 0.06 mmol/L.
- Neuronal consumption of beta-hydroxybutyrate was estimated at 0.032 +/- 0.009 mmol.kg-1.min-1, contributing 6.4% to acetyl-CoA oxidation.
Conclusions:
- Beta-hydroxybutyrate is rapidly utilized in the human brain, with minimal accumulation.
- Neuronal metabolism is the predominant pathway for beta-hydroxybutyrate consumption.
- The blood-brain barrier appears to control ketone oxidation rates in the non-fasted adult brain.