High-Fat Diet Triggers Inflammation-Induced Cleavage of SIRT1 in Adipose Tissue To Promote Metabolic Dysfunction

被引:304
作者
Chalkiadaki, Angeliki [1 ,2 ]
Guarente, Leonard [1 ,2 ]
机构
[1] MIT, Paul F Glenn Lab, Cambridge, MA 02139 USA
[2] MIT, Dept Biol, Cambridge, MA 02139 USA
关键词
ACTIVATED RECEPTOR-GAMMA; INSULIN-RESISTANCE; PPAR-GAMMA; OBESITY; ADIPOCYTES; DEGRADATION; INCREASES; PROTECTS; MICE;
D O I
10.1016/j.cmet.2012.07.003
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Adipose tissue plays an important role in storing excess nutrients and preventing ectopic lipid accumulation in other organs. Obesity leads to excess lipid storage in adipocytes, resulting in the generation of stress signals and the derangement of metabolic functions. SIRT1 is an important regulatory sensor of nutrient availability in many metabolic tissues. Here we report that SIRT1 functions in adipose tissue to protect from inflammation and obesity under normal feeding conditions, and to forestall the progression to metabolic dysfunction under dietary stress and aging. Genetic ablation of SIRT1 in adipose tissue leads to gene expression changes that highly overlap with changes induced by high-fat diet in wild-type mice, suggesting that dietary stress signals inhibit the activity of SIRT1. Indeed, we show that high-fat diet induces the cleavage of SIRT1 protein in adipose tissue by the inflammation-activated caspase-1, providing a link between dietary stress and predisposition to metabolic dysfunction.
引用
收藏
页码:180 / 188
页数:9
相关论文
共 25 条
[1]   SirT1 Gain of Function Increases Energy Efficiency and Prevents Diabetes in Mice [J].
Banks, Alexander S. ;
Kon, Ning ;
Knight, Colette ;
Matsumoto, Michihiro ;
Gutierrez-Juarez, Roger ;
Rossetti, Luciano ;
Gu, Wei ;
Accili, Domenico .
CELL METABOLISM, 2008, 8 (04) :333-341
[2]   SIRT1 transgenic mice show phenotypes resembling calorie restriction [J].
Bordone, Laura ;
Cohen, Dena ;
Robinson, Ashley ;
Motta, Maria Carla ;
van Veen, Ed ;
Czopik, Agnieszka ;
Steele, Andrew D. ;
Crowe, Hayley ;
Marmor, Stephen ;
Luo, Jianyuan ;
Gu, Wei ;
Guarente, Leonard .
AGING CELL, 2007, 6 (06) :759-767
[3]   Specific SIRT1 Activation Mimics Low Energy Levels and Protects against Diet-induced Metabolic Disorders by Enhancing Fat Oxidation [J].
Feige, Jerome N. ;
Lagouge, Marie ;
Canto, Carles ;
Strehle, Axelle ;
Houten, Sander M. ;
Milne, Jill C. ;
Lambert, Philip D. ;
Mataki, Chikage ;
Elliott, Peter J. ;
Auwerx, Johan .
CELL METABOLISM, 2008, 8 (05) :347-358
[4]   Sirtuin 1 (SIRT1) Protein Degradation in Response to Persistent c-Jun N-terminal Kinase 1 (JNK1) Activation Contributes to Hepatic Steatosis in Obesity [J].
Gao, Zhanguo ;
Zhang, Jin ;
Kheterpal, Indu ;
Kennedy, Norm ;
Davis, Roger J. ;
Ye, Jianping .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (25) :22227-22234
[5]   SirT1 Regulates Adipose Tissue Inflammation [J].
Gillum, Matthew P. ;
Kotas, Maya E. ;
Erion, Derek M. ;
Kursawe, Romy ;
Chatterjee, Paula ;
Nead, Kevin T. ;
Muise, Eric S. ;
Hsiao, Jennifer J. ;
Frederick, David W. ;
Yonemitsu, Shin ;
Banks, Alexander S. ;
Qiang, Li ;
Bhanot, Sanjay ;
Olefsky, Jerrold M. ;
Sears, Dorothy D. ;
Caprio, Sonia ;
Shulman, Gerald I. .
DIABETES, 2011, 60 (12) :3235-3245
[6]   Sirtuins as potential targets for metabolic syndrome [J].
Guarente, Leonard .
NATURE, 2006, 444 (7121) :868-874
[7]   Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes [J].
Guilherme, Adilson ;
Virbasius, Joseph V. ;
Puri, Vishwajeet ;
Czech, Michael P. .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2008, 9 (05) :367-377
[8]   Tumor Necrosis Factor-α Induces Caspase-mediated Cleavage of Peroxisome Proliferator-activated Receptor γ in Adipocytes [J].
Guilherme, Adilson ;
Tesz, Gregory J. ;
Guntur, Kalyani V. P. ;
Czech, Michael P. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (25) :17082-17091
[9]   Caspase-mediated degradation of PPARγ proteins in adipocytes [J].
He, Fang ;
Doucet, Julie A. ;
Stephens, Jacqueline M. .
OBESITY, 2008, 16 (08) :1735-1741
[10]   Adipose-specific peroxisome proliferator-activated receptor γ knockout causes insulin resistance in fat and liver but not in muscle [J].
He, WM ;
Barak, Y ;
Hevener, A ;
Olson, P ;
Liao, D ;
Le, J ;
Nelson, M ;
Ong, E ;
Olefsky, JM ;
Evans, RM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (26) :15712-15717