title: Rapid adaptation of rat brain and liver metabolism to a ketogenic diet: an integrated study using (1)H- and (13)C-NMR spectroscopy.
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 control.
authors.affiliation: 1] Research Center on Aging, Université de Sherbrooke, Sherbrooke, Quebec, Canada [2] Department of Physiology and Biophysics, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
authors.forename: Maggie
authors.initials: M
authors.lastname: Roy
authors.affiliation: Centre de Résonance Magnétique des Systèmes Biologiques, UMR5536 CNRS, LabEx TRAIL-IBIO, Université de Bordeaux, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Beauvieux
authors.affiliation: Centre de Résonance Magnétique des Systèmes Biologiques, UMR5536 CNRS, LabEx TRAIL-IBIO, Université de Bordeaux, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Naulin
authors.affiliation: Centre de Résonance Magnétique des Systèmes Biologiques, UMR5536 CNRS, LabEx TRAIL-IBIO, Université de Bordeaux, France.
authors.forename: Dounia
authors.initials: D
authors.lastname: El Hamrani
authors.affiliation: Department of Medicine, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Gallis
authors.affiliation: 1] Research Center on Aging, Université de Sherbrooke, Sherbrooke, Quebec, Canada [2] Department of Physiology and Biophysics, Université de Sherbrooke, Sherbrooke, Quebec, Canada [3] Department of Medicine, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Cunnane
authors.affiliation: Centre de Résonance Magnétique des Systèmes Biologiques, UMR5536 CNRS, LabEx TRAIL-IBIO, Université de Bordeaux, France.
authors.forename: Anne-Karine
authors.initials: AK
authors.lastname: Bouzier-Sore
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D000597:Amino Acids, Branched-Chain / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D055423:Diet, Ketogenic; D004827:Epilepsy / Q000178:diet therapy / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D007657:Ketone Bodies / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000596:Amino Acids; D000597:Amino Acids, Branched-Chain; D007657:Ketone Bodies; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid