Document Detail


Interdependence of AMPK and SIRT1 for metabolic adaptation to fasting and exercise in skeletal muscle.
MedLine Citation:
PMID:  20197054     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
During fasting and after exercise, skeletal muscle efficiently switches from carbohydrate to lipid as the main energy source to preserve glycogen stores and blood glucose levels for glucose-dependent tissues. Skeletal muscle cells sense this limitation in glucose availability and transform this information into transcriptional and metabolic adaptations. Here we demonstrate that AMPK acts as the prime initial sensor that translates this information into SIRT1-dependent deacetylation of the transcriptional regulators PGC-1alpha and FOXO1, culminating in the transcriptional modulation of mitochondrial and lipid utilization genes. Deficient AMPK activity compromises SIRT1-dependent responses to exercise and fasting, resulting in impaired PGC-1alpha deacetylation and blunted induction of mitochondrial gene expression. Thus, we conclude that AMPK acts as the primordial trigger for fasting- and exercise-induced adaptations in skeletal muscle and that activation of SIRT1 and its downstream signaling pathways are improperly triggered in AMPK-deficient states.
Authors:
Carles Cantó; Lake Q Jiang; Atul S Deshmukh; Chikage Mataki; Agnes Coste; Marie Lagouge; Juleen R Zierath; Johan Auwerx
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cell metabolism     Volume:  11     ISSN:  1932-7420     ISO Abbreviation:  Cell Metab.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-03-03     Completed Date:  2010-08-06     Revised Date:  2013-05-30    
Medline Journal Info:
Nlm Unique ID:  101233170     Medline TA:  Cell Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  213-9     Citation Subset:  IM    
Copyright Information:
2010 Elsevier Inc. All rights reserved.
Affiliation:
Ecole Polytechnique Fédérale de Lausanne, Switzerland.
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MeSH Terms
Descriptor/Qualifier:
AMP-Activated Protein Kinases / genetics*,  metabolism
Animals
Cells, Cultured
Energy Metabolism
Fasting / metabolism*
Forkhead Transcription Factors / genetics,  metabolism*
Genes, Mitochondrial / genetics
Glucose / metabolism
Lipids / genetics
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Muscle, Skeletal / metabolism*
Physical Conditioning, Animal / physiology*
Signal Transduction
Sirtuin 1 / genetics,  metabolism*
Trans-Activators / genetics,  metabolism*
Up-Regulation / genetics
Grant Support
ID/Acronym/Agency:
231138//European Research Council; DK59820/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Forkhead Transcription Factors; 0/Foxo1 protein, mouse; 0/Lipids; 0/Ppargc1a protein, mouse; 0/Trans-Activators; 50-99-7/Glucose; EC 2.7.11.1/AMP-Activated Protein Kinases; EC 2.7.11.1/AMPK alpha1 subunit, mouse; EC 2.7.11.1/Prkag3 protein, mouse; EC 3.5.1.-/Sirt1 protein, mouse; EC 3.5.1.-/Sirtuin 1
Comments/Corrections

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