Cited by 320Sirtuins and Resveratrol in MedicineAdipose Tissue and MetabolismAdipokines, Inflammation, and Metabolic Diseases

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SIRT6 protects against pathological damage caused by diet‐induced obesity

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Kanfi, Yariv, Peshti, Victoria, Gil, Reuven, Naiman, Shoshana, Nahum, Liat, Levin, Eran, Kronfeld‐Schor, Noga, Cohen, Haim Y.·2010·Aging Cell

DOI 10.1111/j.1474-9726.2009.00544.x

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Abstract

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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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.
ORCID: Levin, Eran
Kronfeld‐Schor, Noga
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
DOI: 10.1111/j.1474-9726.2009.00544.x
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
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
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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SIRT6 protects against pathological damage caused by diet‐induced obesity

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