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SIRT6 protects against pathological damage caused by diet‐induced obesity
Open accessAbstract
The NAD+-dependent SIRT6 deacetylase is a therapeutic candidate against the emerging metabolic syndrome epidemic. SIRT6, whose deficiency in mice results in premature aging phenotypes and metabolic defects, was implicated in a calorie restriction response that showed an opposite set of phenotypes from the metabolic syndrome. To explore the role of SIRT6 in metabolic stress, wild type and transgenic (TG) mice overexpressing SIRT6 were fed a high fat diet. In comparison to their wild-type littermates, SIRT6 TG mice accumulated significantly less visceral fat, LDL-cholesterol, and triglycerides. TG mice displayed enhanced glucose tolerance along with increased glucose-stimulated insulin secretion. Gene expression analysis of adipose tissue revealed that the positive effect of SIRT6 overexpression is associated with down regulation of a selective set of peroxisome proliferator-activated receptor-responsive genes, and genes associated with lipid storage, such as angiopoietin-like protein 4, adipocyte fatty acid-binding protein, and diacylglycerol acyltransferase 1, which were suggested as potential targets for drugs to control metabolic syndrome. These results demonstrate a protective role for SIRT6 against the metabolic consequences of diet-induced obesity and suggest a potentially beneficial effect of SIRT6 activation on age-related metabolic diseases.
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“mice overexpressing SIRT6 exhibit extended mean and median lifespans, concomitant with improved metabolic function17 and cancer resistance18.”
From SIRT6 represses LINE1 retrotransposons by ribosylating KAP1 but this repression fails with stress and age (2014) · cites this paper as [17]
In the citing paper
“Several mouse models have suggested that SIRT6 is a key regulator of mammalian lifespan.”
From SIRT6 represses LINE1 retrotransposons by ribosylating KAP1 but this repression fails with stress and age (2014) · cites this paper as [17]
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“SIRT6 overexpression lowers LDL and triglyceride levels, improves glucose tolerance (4), and increases lifespan of male mice (5).”
BackgroundSirtuins and NAD + in the Development and Treatment of Metabolic and Cardiovascular Diseases
Kane, A. E., & Sinclair, D. A. (2018) · Circulation Research · doi:10.1161/circresaha.118.312498 · Cited by 497
Metadata
- Authors
- Kanfi, Y., Peshti, V., Gil, R., Naiman, S., Nahum, L., Levin, E., Kronfeld‐Schor, N., & Cohen, H. Y.
- Affiliations
- Bar-Ilan University (IL)
- Tel Aviv University (IL)
- Corresponding author
- Cohen, Haim Y.
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2010-03-16
- Volume
- 9
- Issue
- 2
- Pages
- 162-173
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- OpenAlex
- W2025668535
- Cited by
- 311
- References
- 48
- Citations by year
- 2026: 6 · 2025: 15 · 2024: 20 · 2023: 22 · 2022: 16 · 2021: 26 · 2020: 22 · 2019: 21 · 2018: 16 · 2017: 24 · 2016: 21 · 2015: 17 · 2014: 18 · 2013: 23 · 2012: 19
- FWCI
- 10.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Aging Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Health, State of Israel
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- SIRT6, NAD+-dependent deacetylase, diet-induced obesity, metabolic syndrome, visceral fat accumulation, glucose tolerance, insulin secretion, adipose tissue gene expression, peroxisome proliferator-activated receptors, fat deposition, ANGPTL4, adipocyte fatty acid-binding protein, diacylglycerol acyltransferase 1
- MeSH terms
- Animals, Animal Feed, Fats, Gene Expression Regulation, Homeostasis, Male, Mice, Transgenic, Obesity, Sirtuins, PPAR gamma, Lipid Metabolism, Mice
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