TY - JOUR
T1 - SIRT6 protects against pathological damage caused by diet-induced obesity
AU - Kanfi, Yariv
AU - Peshti, Victoria
AU - Gil, Reuven
AU - Naiman, Shoshana
AU - Nahum, Liat
AU - Levin, Eran
AU - Kronfeld-Schor, Noga
AU - Cohen, Haim Y.
PY - 2010/4/1
Y1 - 2010/4/1
N2 - 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.
AB - 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.
KW - Diet-induced obesity
KW - Metabolic syndrome
KW - SIRT6
UR - http://www.scopus.com/inward/record.url?scp=77953244349&partnerID=8YFLogxK
U2 - 10.1111/j.1474-9726.2009.00544.x
DO - 10.1111/j.1474-9726.2009.00544.x
M3 - Article
C2 - 20047575
AN - SCOPUS:77953244349
SN - 1474-9718
VL - 9
SP - 162
EP - 173
JO - Aging Cell
JF - Aging Cell
IS - 2
ER -