3‐Hydroxybutyrate regulates energy metabolism and induces BDNF expression in cerebral cortical neurons
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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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The ketone β-hydroxybutyrate raises NAD+ in neurons and suppresses Aβ and p-Tau pathologies and ameliorates behavioral deficits in a mouse model of AD.
“the ketone β-hydroxybutyrate, which elevates NAD+ levels in neurons and has been shown to suppress Aβ and p-Tau pathologies and ameliorate behavioral deficits in a mouse model of AD”
From NAD+ in Brain Aging and Neurodegenerative Disorders (2019) · cites this paper as Marosi et al., 2016
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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
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2016-11-14
- Volume
- 139
- Issue
- 5
- Pages
- 769-781
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- 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
- 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 › 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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