Cited by 242Diet and metabolism studiesMitochondrial Function and PathologyNeuroscience and Neuropharmacology Research

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3‐Hydroxybutyrate regulates energy metabolism and induces BDNF expression in cerebral cortical neurons

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Marosi, Krisztina, Kim, Sang Woo, Moehl, Keelin, Scheibye‐Knudsen, Morten, Cheng, Aiwu, Cutler, Roy, Camandola, Simonetta, Mattson, Mark P.·2016·Journal of Neurochemistry

DOI 10.1111/jnc.13868PMC PMC5123937

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Abstract

During fasting and vigorous exercise, a shift of brain cell energy substrate utilization from glucose to the ketone 3‐hydroxybutyrate (3 OHB ) occurs. Studies have shown that 3 OHB can protect neurons against excitotoxicity and oxidative stress, but the underlying mechanisms remain unclear. Neurons maintained in the presence of 3 OHB exhibited increased oxygen consumption and ATP production, and an elevated NAD + / NADH ratio. We found that 3 OHB metabolism increases mitochondrial respiration which drives changes in expression of brain‐derived neurotrophic factor ( BDNF ) in cultured cerebral cortical neurons. The mechanism by which 3 OHB induces Bdnf gene expression involves generation of reactive oxygen species, activation of the transcription factor NF ‐κB, and activity of the histone acetyltransferase p300/ EP 300. Because BDNF plays important roles in synaptic plasticity and neuronal stress resistance, our findings suggest cellular signaling mechanisms by which 3 OHB may mediate adaptive responses of neurons to fasting, exercise, and ketogenic diets. image

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Authors: Marosi, K., Kim, S. W., Moehl, K., Scheibye‐Knudsen, M., Cheng, A., Cutler, R., Camandola, S., & Mattson, M. P.
Affiliations: National Institute on Aging (US)
University of Copenhagen (DK)
Johns Hopkins University (US)
Corresponding author: Mattson, Mark P.
ORCID: Kim, Sang Woo
Moehl, Keelin
Scheibye‐Knudsen, Morten
Cutler, Roy
Camandola, Simonetta
Mattson, Mark P.
Venue: Journal of Neurochemistry
Publisher: Wiley
Published: 2016-11-14
Volume: 139
Issue: 5
Pages: 769-781
ISSN: 0022-3042 (ISSN-L)
1471-4159
DOI: 10.1111/jnc.13868
PMC: PMC5123937
OpenAlex: W2531271987
Cited by: 242
References: 84
Citations by year: 2026: 16 · 2025: 21 · 2024: 25 · 2023: 24 · 2022: 34 · 2021: 32 · 2020: 27 · 2019: 25 · 2018: 19 · 2017: 17 · 2016: 2
FWCI: 16.91
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Journal of Neurochemistry (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Funders: National Institute on Aging
Topics: Health Sciences › Medicine › Physiology (medical) › Diet and metabolism studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: beta-hydroxybutyrate, brain-derived neurotrophic factor, cortical neurons, brain energy metabolism, ketone bodies, mitochondrial respiration, reactive oxygen species, NF-κB, NAD+/NADH ratio, fasting, physical activity, ketogenic diet
MeSH terms: Animals, Cell Survival, Cells, Cultured, Cerebral Cortex, Energy Metabolism, Humans, Male, Mice, Inbred C57BL, Neurons, Gene Expression, Rats, Sprague-Dawley, Brain-Derived Neurotrophic Factor, 3-Hydroxybutyric Acid, Mice, Rats, HEK293 Cells

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3‐Hydroxybutyrate regulates energy metabolism and induces BDNF expression in cerebral cortical neurons

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