Rapid adaptation of rat brain and liver metabolism to a ketogenic diet: an integrated study using (1)H- and (13)C-NMR spectroscopy

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism
Maggie RoyAnne-Karine Bouzier-Sore

Abstract

The ketogenic diet (KD) is an effective alternative treatment for refractory epilepsy in children, but the mechanisms by which it reduces seizures are poorly understood. To investigate how the KD modifies brain metabolism, we infused control (CT) and 7-day KD rats with either [1-(13)C]glucose (Glc) or [2,4-(13)C2]β-hydroxybutyrate (β-HB). Specific enrichments of amino acids (AAs) measured by (1)H- and (13)C-NMR in total brain perchloric acid extracts were similar between CT and KD rats after [1-(13)C]Glc infusion whereas they were higher in KD rats after [2,4-(13)C2]β-HB infusion. This suggests better metabolic efficiency of ketone body utilization on the KD. The relative rapid metabolic adaptation to the KD included (1) 11%-higher brain γ-amino butyric acid (GABA)/glutamate (Glu) ratio versus CT, (2) liver accumulation of the ketogenic branched-chain AAs (BCAAs) leucine (Leu) and isoleucine (ILeu), which were never detected in CT, and (3) higher brain Leu and ILeu contents. Since Glu and GABA are excitatory and inhibitory neurotransmitters, respectively, higher brain GABA/Glu ratio could contribute to the mechanism by which the KD reduces seizures in epilepsy. Increased BCAA on the KD may also contribute to better seizure cont...Continue Reading

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Citations

Jan 15, 2016·Annals of the New York Academy of Sciences·Stephen C CunnaneChristian-Alexandre Castellano
Jul 28, 2016·Frontiers in Molecular Neuroscience·Stephen C CunnaneChristian-Alexandre Castellano
Feb 11, 2018·Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine·Blanca LizarbeRolf Gruetter
Jun 13, 2019·Acta Neuropsychiatrica·Brian E Leonard, Gregers Wegener
Jul 28, 2020·Nature Reviews. Drug Discovery·Stephen C CunnaneMark J Millan
Aug 23, 2017·Annual Review of Nutrition·John C Newman, Eric Verdin
Feb 6, 2017·Frontiers in Neuroscience·Alexandria Béland-MillarClaude Messier
May 1, 2019·American Journal of Physiology. Endocrinology and Metabolism·Caitlyn E BowmanMichael J Wolfgang

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Methods Mentioned

BETA
NMR
ELISA

Software Mentioned

Prism
GraphPad
ARRIVE
GSim

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