Ketone bodies as signaling metabolites
Open accessAbstract
Traditionally, the ketone body β-hydroxybutyrate (βOHB) has been looked upon as a carrier of energy from liver to peripheral tissues during fasting or exercise. However, βOHB also signals via extracellular receptors and acts as an endogenous inhibitor of histone deacetylases (HDACs). These recent findings support a model in which βOHB functions to link the environment, in this case the diet, and gene expression via chromatin modifications. We review the regulation and functions of ketone bodies, the relationship between ketone bodies and calorie restriction, and the implications of HDAC inhibition by the ketone body βOHB in the modulation of metabolism and in diseases of aging.
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Ketone bodies are synthesised in the mitochondria by the liver through a metabolic process known as ketogenesis.
“They are synthesised in the mitochondria by the liver through a metabolic process known as ketogenesis [191].”
From Regulation of Energy Substrate Metabolism in Endurance Exercise (2021) · cites this paper as [191]
The central precursor for the ketogenic process is acetyl CoA, derived predominantly from excessive oxidation of fatty acid, which in turn is converted into acetoacetate, β hydroxy butyrate and acetone.
“The central precursor for the ketogenic process is acetyl CoA, derived predominantly from excessive oxidation of fatty acid, which in turn is converted into acetoacetate, β hydroxy butyrate and acetone.”
From Regulation of Energy Substrate Metabolism in Endurance Exercise (2021) · cites this paper as [191]
Ketone bodies possess signaling activities.
“In addition to its crucial role in intermediary metabolism, ketone bodies also possess signaling activities (Newman & Verdin, 2014).”
From The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, and Metabolic and Disease Implications (2018) · cites this paper as Newman & Verdin, 2014
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“…studies should examine how innate immunity, particularly the inflammasome, is influenced by ketones and other alternative metabolic fuels during periods of energy deficiency (Shido et al., 1989; Johnson et al., 2007; McGettrick and O’Neill, 2013; Mercken et al., 2013; Newman and Verdin, 2014).”
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- Authors
- Newman, J. C., & Verdin, E.
- Affiliations
- Gladstone Institutes (US)
- Corresponding author
- Verdin, Eric
- ORCID
- Verdin, Eric
- Venue
- Trends in Endocrinology & Metabolism
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 25
- Issue
- 1
- Pages
- 42-52
- ISSN
- 1043-2760 (ISSN-L)
- PMC
- PMC4176946
- OpenAlex
- W2036551825
- Cited by
- 966
- References
- 143
- Citations by year
- 2026: 71 · 2025: 98 · 2024: 87 · 2023: 78 · 2022: 117 · 2021: 105 · 2020: 98 · 2019: 77 · 2018: 71 · 2017: 72 · 2016: 43 · 2015: 27 · 2014: 22
- FWCI
- 3.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Trends in Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- John A. Hartford Foundation
- Larry L. Hillblom Foundation
- Glenn Foundation for Medical Research
- National Institutes of Health
- National Institute on Aging (K08AG048354, T32AG000212)
- National Institute of Diabetes and Digestive and Kidney Diseases
- Topics
- Health Sciences › Medicine › Physiology › Diet and metabolism studies
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Keywords
- ketone bodies, beta-hydroxybutyrate, histone deacetylase inhibition, chromatin modification, gene expression regulation, caloric restriction, fasting, physical activity, aging, metabolism
- MeSH terms
- Aging, Animals, Histone Deacetylases, Humans, Ketone Bodies, Signal Transduction, 3-Hydroxybutyric Acid, Monocarboxylic Acid Transporters, Caloric Restriction, Histone Deacetylase Inhibitors
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