Cited by 873Diet and metabolism studiesDietary Effects on HealthMetabolism and Genetic Disorders

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β-Hydroxybutyrate: A Signaling Metabolite

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Newman, John C., Verdin, Eric·2017·Annual Review of Nutrition

DOI 10.1146/annurev-nutr-071816-064916PMC PMC6640868

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Abstract

Various mechanisms in the mammalian body provide resilience against food deprivation and dietary stress. The ketone body β-hydroxybutyrate (BHB) is synthesized in the liver from fatty acids and represents an essential carrier of energy from the liver to peripheral tissues when the supply of glucose is too low for the body's energetic needs, such as during periods of prolonged exercise, starvation, or absence of dietary carbohydrates. In addition to its activity as an energetic metabolite, BHB is increasingly understood to have cellular signaling functions. These signaling functions of BHB broadly link the outside environment to epigenetic gene regulation and cellular function, and their actions may be relevant to a variety of human diseases as well as human aging.

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Muoio, D. M., Noland, R. C., Kovalik, J.-P., Seiler, S. E., Davies, M. N., DeBalsi, K. L., Ilkayeva, O. R., Stevens, R. D., Kheterpal, I., Zhang, J., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.04.005 · Cited by 372 · cited 2×
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β-hydroxybutyrate deactivates neutrophil NLRP3 inflammasome to relieve gout flares
Goldberg, E. L., Asher, J. L., Molony, R. D., Shaw, A. C., Zeiss, C. J., Wang, C., Morozova-Roche, L. A., Herzog, R. I., Iwasaki, A., & Dixit, V. D. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.02.004 · Cited by 370 · cited 1×
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Layden, B. T., Angueira, A. R., Brodsky, M. R., Durai, V., & Lowe, W. L. (2012) · Translational research · doi:10.1016/j.trsl.2012.10.007 · Cited by 366 · cited 1×
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Hdac3 is essential for the maintenance of chromatin structure and genome stability
Bhaskara, S., Knutson, S. K., Jiang, G., Chandrasekharan, M. B., Wilson, A. J., Zheng, S., Yenamandra, A., Locke, K., Yuan, J.-L., Bonine-Summers, A. R., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.10.022 · Cited by 353 · cited 1×
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Ketogenic Diet Metabolites Reduce Firing in Central Neurons by Opening K ATP Channels
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β-Hydroxybutyrate Modulates N-Type Calcium Channels in Rat Sympathetic Neurons by Acting as an Agonist for the G-Protein-Coupled Receptor FFA3
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Histone deacetylase (HDAC) inhibition improves myocardial function and prevents cardiac remodeling in diabetic mice
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Ketone bodies do not directly alter excitatory or inhibitory hippocampal synaptic transmission
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Influential
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“The method used to detect K(BHB) could not distinguish modification with R-BHB from modification with S-BHB (148), but it is likely that both K(S-BHB) and K(R-BHB) are present.”
Influential
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Jensen, N. J., Wodschow, H. Z., Nilsson, M., & Rungby, J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228767 · Cited by 450
“The enzyme HMG-CoA lyase subsequently removes an acetyl-CoA from HMG-CoA to produce the ketone body acetoacetate, which can either undergo spontaneous degradation to acetone (another ketone body with minimal metabolic contribution) or form the ketone body beta-hydroxybutyrate (BHB) [20], the most abundant ketone body…”
Background

See all 873

Authors: Newman, J. C., & Verdin, E.
Affiliations: Gladstone Institutes (US)
ORCID: Verdin, Eric
Venue: Annual Review of Nutrition
Publisher: Annual Reviews
Published: 2017-08-21
Volume: 37
Issue: 1
Pages: 51-76
ISSN: 0199-9885 (ISSN-L)
1545-4312
DOI: 10.1146/annurev-nutr-071816-064916
PMC: PMC6640868
OpenAlex: W2747163024
Cited by: 872
References: 163
Citations by year: 2026: 146 · 2025: 160 · 2024: 126 · 2023: 100 · 2022: 106 · 2021: 99 · 2020: 72 · 2019: 38 · 2018: 24 · 2017: 1
FWCI: 4.53
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.annualreviews.org/licenses/tdm (tdm)
Locations: Annual Review of Nutrition (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
National Institute on Aging (K08AG048354)
National Institute of Diabetes and Digestive and Kidney Diseases (R24DK085610)
Topics: Health Sciences › Medicine › Physiology (medical) › Diet and metabolism studies
Health Sciences › Medicine › Physiology (medical) › Dietary Effects on Health
Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
Keywords: beta-hydroxybutyrate, ketone bodies, signal transduction, epigenetic regulation, energy metabolism, fasting, starvation, physical activity, nutritional stress, aging
MeSH terms: Aging, Animals, Humans, Liver, Starvation, Signal Transduction, 3-Hydroxybutyric Acid, Epigenesis, Genetic

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β-Hydroxybutyrate: A Signaling Metabolite

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