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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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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