Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-3-3
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1932-7420
pubmed:author
pubmed:copyrightInfo
2010 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
3
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
213-9
pubmed:dateRevised
2010-10-8
pubmed:meshHeading
pubmed-meshheading:20197054-AMP-Activated Protein Kinases, pubmed-meshheading:20197054-Animals, pubmed-meshheading:20197054-Cells, Cultured, pubmed-meshheading:20197054-Energy Metabolism, pubmed-meshheading:20197054-Fasting, pubmed-meshheading:20197054-Forkhead Transcription Factors, pubmed-meshheading:20197054-Genes, Mitochondrial, pubmed-meshheading:20197054-Glucose, pubmed-meshheading:20197054-Lipids, pubmed-meshheading:20197054-Male, pubmed-meshheading:20197054-Mice, pubmed-meshheading:20197054-Mice, Inbred C57BL, pubmed-meshheading:20197054-Mice, Knockout, pubmed-meshheading:20197054-Muscle, Skeletal, pubmed-meshheading:20197054-Physical Conditioning, Animal, pubmed-meshheading:20197054-Signal Transduction, pubmed-meshheading:20197054-Sirtuin 1, pubmed-meshheading:20197054-Trans-Activators, pubmed-meshheading:20197054-Up-Regulation
pubmed:year
2010
pubmed:articleTitle
Interdependence of AMPK and SIRT1 for metabolic adaptation to fasting and exercise in skeletal muscle.
pubmed:affiliation
Ecole Polytechnique Fédérale de Lausanne, Switzerland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural