ArticleInternational journal of molecular sciences2021
Ingested Ketone Ester Leads to a Rapid Rise of Acetyl-CoA and Competes with Glucose Metabolism in the Brain of Non-Fasted Mice.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
- Intermittent exogenous ketosis does not reduce acute mountain sickness during early terrestrial high-altitude acclimatization.European journal of applied physiology · 2026Article
- Redox coupling of lactate and β-hydroxybutyrate: An inter-organ circuit linking metabolic flexibility, mitochondrial adaptation, and disease.Redox biology · 2026Review
- Glycolysis: The Bridge Between Cellular Interaction and Alzheimer's Disease.Biomolecules · 2026Review
- NLRP3 inflammasome blockade treats intestinal inflammation associated with chronic granulomatous disease.Blood · 2026Article
- β-Hydroxybutyrate, a primary metabolite of ketogenic diets and its dual role in modulating colorectal cancer: from molecular mechanisms to therapeutic insights.Clinical and experimental medicine · 2026Review
- Ketone bodies mitigate against systemic inflammation-induced changes in brain energy metabolism and delirium-like deficits in aged mice.bioRxiv : the preprint server for biology · 2026Article
- Mediating Role of Plasma Biomarkers Associated with Metabolic Syndrome in Cognitive Decline Among Older Adults.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Article
- β‑hydroxybutyric acid as a potential therapeutic metabolite for type 2 diabetes mellitus (Review).International journal of molecular medicine · 2026Review
- The Effect of Exogenous Ketones on Signs and Symptoms of Schizophrenia Spectrum and Bipolar Disorders: Study Protocol for a Triple-Blind, Randomized, Controlled Crossover Pilot Study.Current developments in nutrition · 2025Article
- Ketone body-supported respiration in murine isolated brain mitochondria is augmented by alpha-ketoglutarate and is optimized by neuronal SCOT expression.American journal of physiology. Endocrinology and metabolism · 2025Article
- Characterizing the Hepatic Metabolic Pathway of Ketone Ester and Subsequent Metabolites Using Human and Rat Liver Fractions.The AAPS journal · 2025Article
- Ketone ester-enriched diet ameliorates motor and dopamine release deficits in MitoPark mice.The European journal of neuroscience · 2024Article
- β-hydroxybutyrate and ischemic stroke: roles and mechanisms.Molecular brain · 2024Review
- Neuroprotective effects of lactate and ketone bodies in acute brain injury.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Review
- Quantitative Determination of (R)-3-Hydroxybutyl (R)-3-Hydroxybutyrate (Ketone Ester) and Its Metabolites Beta-hydroxybutyrate, 1-3-Butanediol, and Acetoacetate in Human Plasma Using LC-MS.AAPS PharmSciTech · 2023Article
- Metabolic and Cellular Compartments of Acetyl-CoA in the Healthy and Diseased Brain.International journal of molecular sciences · 2022Review
- Review
- Unifying mechanism behind the onset of acquired epilepsy.Trends in pharmacological sciences · 2022Review
- Ketone BodyOxidative medicine and cellular longevity · 2022Article
- The Metabolic Effects of Ketones.International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The role of ketone bodies in the cerebral energy homeostasis of neurological diseases has begun to attract recent attention particularly in acute neurological diseases. In ketogenic therapies, ketosis is achieved by either a ketogenic diet or by the administration of exogenous ketone bodies. The oral ingestion of the ketone ester (KE), (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, is a new method to generate rapid and significant ketosis (i.e., above 6 mmol/L) in humans. KE is hydrolyzed into β-hydroxybutyrate (βHB) and its precursor 1,3-butanediol. Here, we investigate the effect of oral KE administration (3 mg KE/g of body weight) on brain metabolism of non-fasted mice using liquid chromatography in tandem with mass spectrometry. Ketosis (Cmax = 6.83 ± 0.19 mmol/L) was obtained at Tmax = 30 min after oral KE-gavage. We found that βHB uptake into the brain strongly correlated with the plasma βHB concentration and was preferentially distributed in the neocortex. We showed for the first time that oral KE led to an increase of acetyl-CoA and citric cycle intermediates in the brain of non-fasted mice. Furthermore, we found that the increased level of acetyl-CoA inhibited glycolysis by a feedback mechanism and thus competed with glucose under physiological conditions. The brain pharmacodynamics of this oral KE strongly suggest that this agent should be considered for acute neurological diseases.
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