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Specific SIRT1 Activation Mimics Low Energy Levels and Protects against Diet-Induced Metabolic Disorders by Enhancing Fat Oxidation
Open accessAbstract
The NAD(+)-dependent deacetylase SIRT1 controls metabolic processes in response to low nutrient availability. We report the metabolic phenotype of mice treated with SRT1720, a specific and potent synthetic activator of SIRT1 that is devoid of direct action on AMPK. SRT1720 administration robustly enhances endurance running performance and strongly protects from diet-induced obesity and insulin resistance by enhancing oxidative metabolism in skeletal muscle, liver, and brown adipose tissue. These metabolic effects of SRT1720 are mediated by the induction of a genetic network controlling fatty acid oxidation through a multifaceted mechanism that involves the direct deacetylation of PGC-1alpha, FOXO1, and p53 and the indirect stimulation of AMPK signaling through a global metabolic adaptation mimicking low energy levels. Combined with our previous work on resveratrol, the current study further validates SIRT1 as a target for the treatment of metabolic disorders and characterizes the mechanisms underlying the therapeutic potential of SIRT1 activation.
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“In the cases of resveratrol and the sirtuin activator SRT1720, there is convincing evidence that they protect from metabolic damage and improve mitochondrial respiration in a PGC-1α-dependent fashion”
From The Hallmarks of Aging (2013) · cites this paper as Feige et al., 2008
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“However, SRT1720 has been shown in BAT to modify lipid droplet size and gene expression 157,158.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [158]
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Metadata
- Authors
- Feige, J. N., Lagouge, M., Canto, C., Strehle, A., Houten, S. M., Milne, J. C., Lambert, P. D., Mataki, C., Elliott, P. J., & Auwerx, J.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Amsterdam UMC Location University of Amsterdam (NL)
- Corresponding author
- Auwerx, Johan
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2008-11
- Volume
- 8
- Issue
- 5
- Pages
- 347-358
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2077834313
- Cited by
- 719
- References
- 39
- Citations by year
- 2026: 7 · 2025: 15 · 2024: 19 · 2023: 22 · 2022: 22 · 2021: 30 · 2020: 29 · 2019: 28 · 2018: 42 · 2017: 28 · 2016: 41 · 2015: 51 · 2014: 58 · 2013: 64 · 2012: 63
- FWCI
- 27.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- HAL (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- SIRT1, SRT1720, NAD+-dependent deacetylase, fatty acid oxidation, diet-induced obesity, insulin resistance, AMPK signaling, PGC-1α, FOXO1, p53, brown adipose tissue, skeletal muscle metabolism, hepatic metabolism, endurance running performance, low energy availability, metabolic adaptation, resveratrol, metabolic disorders
- MeSH terms
- Acetylation, Animals, Diet, Dietary Fats, Energy Metabolism, Heterocyclic Compounds, 4 or More Rings, Insulin Resistance, Male, Metabolic Diseases, Mice, Inbred C57BL, Motor Activity, Obesity, Oxidation-Reduction, Physical Conditioning, Animal, Sirtuins, Lipid Metabolism, Mice, Sirtuin 1
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