Specific SIRT1 Activation Mimics Low Energy Levels and Protects against Diet-Induced Metabolic Disorders by Enhancing Fat Oxidation
Cell Metabolism, Volume 9, Issue 2, 4 February 2009, Page 210,
Jérôme N. Feige, Marie Lagouge, Carles Canto, Axelle Strehle, Sander M. Houten, Jill C. Milne, Philip D. Lambert, Chikage Mataki, Peter J. Elliott, Johan Auwerx
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Summary
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-1α, 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.
Author Keywords: HUMDISEASE
Article Outline
Introduction
Results
SRT1720 Is a Potent and Specific Activator of SIRT1
SRT1720 Protects from Diet-Induced Diabesity
SRT1720 Promotes Energy Expenditure in Metabolic Tissues
SRT1720 Administration Mechanistically Mimics Low Energy Levels
Discussion
Experimental Procedures
Chemicals and Reagents
Animal Experiments
Biochemistry and Immunoblotting
Gene Expression Profiling
Oxygen Consumption Measurements
Statistics
Acknowledgements
Supplemental Data
References
Interesting that SRT1720 isstated not to directly activate AMPK, whereas I believe resveratrol does activate it.
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