The DOI matches its Crossref record; 143 of the 143 references it cites were found in a registry or an index.
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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“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]
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“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]
In the citing paper
“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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Citations
Cites
Database resources of the National Center for Biotechnology Information: update
Wheeler, D. L. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkh073 · Cited by 10,695
Anticancer activities of histone deacetylase inhibitors
Bolden, J. E., Peart, M. J., & Johnstone, R. W. (2006) · Nature Reviews Drug Discovery · doi:10.1038/nrd2133 · Cited by 2,919
Kenyon, C. J. (2010) · Nature · doi:10.1038/nature08980 · Cited by 2,739
ATP-citrate lyase links cellular metabolism to histone acetylation
Wellen, K. E., Hatzivassiliou, G., Sachdeva, U. M., Bui, T. V., Cross, J. R., & Thompson, C. B. (2009) · Science · doi:10.1126/science.1164097 · Cited by 2,298
Butyrate improves insulin sensitivity and increases energy expenditure in mice
Gao, Z., Yin, J., Zhang, J., Ward, R. E., Martin, R. J., Lefevre, M., Cefalu, W. T., & Ye, J. (2009) · Diabetes · doi:10.2337/db08-1637 · Cited by 2,204
Sirtuins as regulators of metabolism and healthspan
Houtkooper, R. H., Pirinen, E., & Auwerx, J. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3293 · Cited by 2,008
Hatori, M., Vollmers, C., Zarrinpar, A., DiTacchio, L., Bushong, E. A., Gill, S., Leblanc, M., Chaix, A., Joens, M., Fitzpatrick, J. A. J., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.04.019 · Cited by 1,986
Suppression of Oxidative Stress by β-Hydroxybutyrate, an Endogenous Histone Deacetylase Inhibitor
Shimazu, T., Hirschey, M. D., Newman, J., He, W., Shirakawa, K., Le Moan, N., Grueter, C. A., Lim, H., Saunders, L. R., Stevens, R. D., et al. (2013) · Science · doi:10.1126/science.1227166 · Cited by 1,777
Self-citationHDAC2 negatively regulates memory formation and synaptic plasticity
Guan, J.-S., Haggarty, S. J., Giacometti, E., Dannenberg, J.-H., Joseph, N., Gao, J., Nieland, T. J. F., Zhou, Y., Wang, X., Mazitschek, R., et al. (2009) · Nature · doi:10.1038/nature07925 · Cited by 1,644
Acetylation and deacetylation of non-histone proteins
Glozak, M. A., Sengupta, N., Zhang, X., & Seto, E. (2005) · Gene · doi:10.1016/j.gene.2005.09.010 · Cited by 1,584
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The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease
Youm, Y.-H., Nguyen, K. Y., Grant, R. W., Goldberg, E. L., Bodogai, M., Kim, D., D'Agostino, D., Planavsky, N., Lupfer, C., Kanneganti, T. D., et al. (2015) · Nature Medicine · doi:10.1038/nm.3804 · Cited by 2,172
Multi-dimensional Roles of Ketone Bodies in Fuel Metabolism, Signaling, and Therapeutics
Puchalska, P., & Crawford, P. A. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2016.12.022 · Cited by 1,682
Acetyl coenzyme A: a central metabolite and second messenger
Pietrocola, F., Galluzzi, L., Bravo-San Pedro, J. M., Madeo, F., & Kroemer, G. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.05.014 · Cited by 1,378
β-Hydroxybutyrate: A Signaling Metabolite
Newman, J. C., & Verdin, E. (2017) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071816-064916 · Cited by 872
“The data from invertebrate organisms showing that reduction in class I HDAC activity extends life span, and generally acts through similar pathways as dietary restriction, have been reviewed (92).”
Self-citationNLRP3 inflammasome and its inhibitors: a review
Shao, B.-Z., Xu, Z.-Q., Han, B.-Z., Su, D.-F., & Liu, C. (2015) · Frontiers in Pharmacology · doi:10.3389/fphar.2015.00262 · Cited by 836
“…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).”
Background
Metadata
- 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 (medical) › Diet and metabolism studies
- Health Sciences › Medicine › Physiology (medical) › 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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