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β-Hydroxybutyrate: A Signaling Metabolite
Open accessAbstract
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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“The higher rate of sustained remission in the present investigation may be due to sustained carbohydrate restriction and the metabolic benefits attributed to nutritional ketosis [28], as well as the ongoing level of support provided from the care team in this care model.”
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Additional file 3 of Mechanism of reduced muscle atrophy via ketone body (D)-3-hydroxybutyrate
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Additional file 2 of Mechanism of reduced muscle atrophy via ketone body (D)-3-hydroxybutyrate
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Prins, P., D’Agostino, D. P., Rogers, C. Q., Ault, D. L., Welton, G. L., Jones, D. W., Henson, S. R., Rothfuss, T. J., Aiken, K. G., Hose, J. L., et al. (2020) · Figshare · doi:10.6084/m9.figshare.13023650
Additional file 1 of Mechanism of reduced muscle atrophy via ketone body (D)-3-hydroxybutyrate
Chen, J., Li, Z., Zhang, Y., Zhang, X., Zhang, S., Liu, Z., Yuan, H., Pang, X., Liu, Y., Tao, W., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20105521
Hui, S. A., Chiew, A. L., & Depczynski, B. (2023) · Figshare · doi:10.6084/m9.figshare.22721506
THE ROLE OF DIET IN THE PREVENTION OF LIFESTYLE DISEASES: A LITERATURE REVIEW
Janczura, S., Dądela, B., Zielonka, K., Śliwa, N., Markowski, M., Jasińska, J., Kawalska, E., Jakubowska, D., Gnitecki, S., & Borowski, M. (2025) · International Journal of Innovative Technologies in Social Science · doi:10.31435/ijitss.3(47).2025.4203
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Beta hydroxybutyrate alters beta cell identity and function in human isletsPreprint
Chae, Y. S., Mandala, A., de Winter, T. J. J., Hammink, E., van der Wel, E. J., Roodzant, M. J., Carlotti, F., Engelse, M. A., & de Koning, E. J. P. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2025.12.24.696385
High-fructose corn syrup for managing negative energy balance in sheep
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Goand, U. K., Paudel, D., Koehle, A., Hao, F., Nguyen, L. V., Yalavarthi, G., Tian, S., Rajakaruna, S., Robert, C. E. M., da Silva, I. V., et al. (2025) · Journal of Nutrition · doi:10.1016/j.tjnut.2025.101285 · Cited by 1
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Eun, Y., Newman, J. C., Lee, J. H., Kim, S., & Kim, H. (2026) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2026.1768532
“…are endogenous fuels produced by the liver when glucose availability is low, such as during fasting and starvation, a process called ketogenesis (Newman and Verdin, 2017), and include acetoacetate, β -hydroxybutyrate (BHB), and acetone, of which BHB is the most abundant circulating ketone body…”
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“Lower 3-hydroxybutyric acid may indicate reduced ketone availability and/or utilization—an alternative energy substrate with recognized signaling roles that intersect with oxidative stress pathways [15].”
Machine Learning to Tailor Intermittent Fasting for Blood Pressure Improvement
Shazman, S. (2026) · Nutrients · doi:10.3390/nu18040667
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“Research has shown that when mammals are deprived of nutrients, undergo prolonged fasting, or engage in exercise, fatty acid oxidative metabolism is enhanced, resulting in the production of substantial amounts of ketone bodies in the intestine [19].”
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“This (49), and β -hydroxybutyrate–mediated anti-inflammatory effects (histone deacetylase inhibition, NLRP3 inflammasome suppression) (50).”
RetractedCastillo, N. A. L., Khan, H. M., Zotti, T., Pinto, G., Giacco, A., Cerulo, L., Cuomo, A., Cardinale, G., Amoresano, A., Camerini, S., et al. (2026) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00864.2025
Physical activity and microglial metabolism in neurodegenerative diseases
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Revealing gut microbiome alterations in prolonged water only fastingPreprint
Godlewska, U., Pilis, K., Pilis, A., Stec, K., Pilis, W., Nowara, E., & Antosiewicz, J. (2026) · Research Square · doi:10.21203/rs.3.rs-8892199/v1
Metadata
- 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
- 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
- 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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