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β-Hydroxybutyrate Boosts Mitochondrial and Neuronal Metabolism but is not Preferred Over Glucose Under Activated Conditions
- Source :
- Neurochemical research. 42(6)
- Publication Year :
- 2017
-
Abstract
- The ketone body, β-hydroxybutyrate (βOHB), is metabolised by the brain alongside the mandatory brain fuel glucose. To examine the extent and circumstances by which βOHB can supplement glucose metabolism, we studied guinea pig cortical brain slices using increasing concentrations of [U-13C]D-βOHB in conjunction with [1-13C]d-glucose under conditions of normo- and hypoglycaemia, as well as under high potassium (40 mmol/L K+) depolarization in normo- and hypoglycaemic conditions. The contribution of βOHB to synthesis of GABA was also probed by inhibiting the synthesis of glutamine, a GABA precursor, with methionine sulfoximine (MSO). [U-13C]D-βOHB at lower concentrations (0.25 and 1.25 mmol/L) stimulated mitochondrial metabolism, producing greater total incorporation of label into glutamate and GABA but did not have a similar effect in the cytosolic compartment where labelling of glutamine was reduced at 1.25 mmol/L [U-13C]D-βOHB. At higher concentrations (2.5 mmol/L) [U-13C]D-βOHB inhibited metabolism of [1-13C]d-glucose, and reduced total label incorporation and total metabolite pools. When glucose levels were reduced, βOHB was able to partially restore the loss of glutamate and GABA caused by hypoglycaemia, but was not able to supplement levels of lactate, glutamine or alanine or to prevent the increase in aspartate. Under depolarizing conditions glucose was the preferred substrate over βOHB, even in hypoglycaemic conditions where comparatively less βOHB was incorporated except into aspartate isotopomers. Inhibition of glutamine synthesis with MSO had no significant effect on incorporation of label from [U-13C]D-βOHB into GABA C2,1 indicating that the majority of this GABA was synthesized in GABAergic neurons from [U-13C]D-βOHB rather than from Gln C4,5 imported from astrocytes.
- Subjects :
- 0301 basic medicine
Male
medicine.medical_specialty
Metabolite
Glutamine
Guinea Pigs
Carbohydrate metabolism
Biology
Biochemistry
03 medical and health sciences
Cellular and Molecular Neuroscience
chemistry.chemical_compound
0302 clinical medicine
Internal medicine
medicine
Animals
Neurons
3-Hydroxybutyric Acid
Dose-Response Relationship, Drug
Glutamate receptor
General Medicine
Metabolism
Mitochondria
Cytosol
030104 developmental biology
Endocrinology
Glucose
chemistry
Ketone bodies
GABAergic
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 15736903
- Volume :
- 42
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Neurochemical research
- Accession number :
- edsair.doi.dedup.....29de9a5ca3645f9b3b958db20cda93ad