Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Jul 30;14(15):3145.
doi: 10.3390/nu14153145.

Ketone Bodies and SIRT1, Synergic Epigenetic Regulators for Metabolic Health: A Narrative Review

Rossella Tozzi  1 , Fiammetta Cipriani  2 , Davide Masi  2 , Sabrina Basciani  2 , Mikiko Watanabe  2 , Carla Lubrano  2 , Lucio Gnessi  2 , Stefania Mariani  2
Affiliations
Review

Ketone Bodies and SIRT1, Synergic Epigenetic Regulators for Metabolic Health: A Narrative Review

Rossella Tozzi et al. Nutrients. .

Abstract

Ketone bodies (KBs) and Sirtuin-1 (SIRT1) have received increasing attention over the past two decades given their pivotal function in a variety of biological contexts, including transcriptional regulation, cell cycle progression, inflammation, metabolism, neurological and cardiovascular physiology, and cancer. As a consequence, the modulation of KBs and SIRT1 is considered a promising therapeutic option for many diseases. The direct regulation of gene expression can occur in vivo through histone modifications mediated by both SIRT1 and KBs during fasting or low-carbohydrate diets, and dietary metabolites may contribute to epigenetic regulation, leading to greater genomic plasticity. In this review, we provide an updated overview of the epigenetic interactions between KBs and SIRT1, with a particular glance at their central, synergistic roles for metabolic health.

Keywords: NAFLD; SIRT1; epigenetic regulators; ketogenic diet; ketone bodies; obesity; visceral fat; β-OH-butyrate.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of the epigenetic activity of ketone bodies and SIRT1 in response to starvation or to the ketogenic diet. Synergistically, KBs and SIRT1 target both histone and nonhistone proteins and alter cellular metabolic programs. NAD, nicotinamide adenine dinucleotide; PTMs, post-translational modifications.
Figure 2
Figure 2
Schematic representation of the epigenetic control of KBs and SIRT1 on their targets. Post-translational modifications (PTMs) are key mechanisms for epigenetic regulation, which alters the activity of metabolic modulators. Abbreviations: NAD, nicotinamide adenine dinucleotide; AMPK, AMP-activated protein kinase; PPAR-alpha, peroxisome proliferator-activated receptor-α; PPAR-gamma, peroxisome proliferator-activated receptor-γ; PGC1-α, PPARγ-coactivator1-α; FOXO, Forkhead Box O; CRTC2, cAMP response element-binding (CREB)-regulated transcription coactivator 2; UCPs, uncoupling proteins; LXR, liver X receptor; FGF-21, fibroblast growth factor-21.
See this image and copyright information in PMC

References

    1. Castellana M., Conte E., Cignarelli A., Perrini S., Giustina A., Giovanella L., Giorgino F., Trimboli P. Efficacy and Safety of Very Low Calorie Ketogenic Diet (VLCKD) in Patients with Overweight and Obesity: A Systematic Review and Meta-Analysis. Rev. Endocr. Metab. Disord. 2020;21:5–16. doi: 10.1007/s11154-019-09514-y. - DOI - PubMed
    1. Norwitz N.G., Hu M.T., Clarke K. The Mechanisms by Which the Ketone Body D-β-Hydroxybutyrate May Improve the Multiple Cellular Pathologies of Parkinson’s Disease. Front. Nutr. 2019;6:63. doi: 10.3389/fnut.2019.00063. - DOI - PMC - PubMed
    1. Sourbron J., Thevissen K., Lagae L. The Ketogenic Diet Revisited: Beyond Ketones. Front. Neurol. 2021;12:720073. doi: 10.3389/fneur.2021.720073. - DOI - PMC - PubMed
    1. Kennedy A.R., Pissios P., Otu H., Xue B., Asakura K., Furukawa N., Marino F.E., Liu F.-F., Kahn B.B., Libermann T.A., et al. A High-Fat, Ketogenic Diet Induces a Unique Metabolic State in Mice. Am. J. Physiol. Endocrinol. Metab. 2007;292:E1724–E1739. doi: 10.1152/ajpendo.00717.2006. - DOI - PubMed
    1. Caprio M., Infante M., Moriconi E., Armani A., Fabbri A., Mantovani G., Mariani S., Lubrano C., Poggiogalle E., Migliaccio S., et al. Very-Low-Calorie Ketogenic Diet (VLCKD) in the Management of Metabolic Diseases: Systematic Review and Consensus Statement from the Italian Society of Endocrinology (SIE) J. Endocrinol. Investig. 2019;42:1365–1386. doi: 10.1007/s40618-019-01061-2. - DOI - PubMed