Interdependence of AMPK and SIRT1 for metabolic adaptation to fasting and exercise in skeletal muscle
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Interdependence of AMPK and SIRT1 for metabolic adaptation to fasting and exercise in skeletal muscle. / Cantó, Carles; Jiang, Lake Q; Deshmukh, Atul S; Mataki, Chikage; Coste, Agnes; Lagouge, Marie; Zierath, Juleen R; Auwerx, Johan.
In: Cell Metabolism, Vol. 11, No. 3, 03.03.2010, p. 213-9.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Interdependence of AMPK and SIRT1 for metabolic adaptation to fasting and exercise in skeletal muscle
AU - Cantó, Carles
AU - Jiang, Lake Q
AU - Deshmukh, Atul S
AU - Mataki, Chikage
AU - Coste, Agnes
AU - Lagouge, Marie
AU - Zierath, Juleen R
AU - Auwerx, Johan
N1 - 2010 Elsevier Inc. All rights reserved.
PY - 2010/3/3
Y1 - 2010/3/3
N2 - 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.
AB - 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.
KW - AMP-Activated Protein Kinases
KW - Animals
KW - Cells, Cultured
KW - Energy Metabolism
KW - Fasting
KW - Forkhead Box Protein O1
KW - Forkhead Transcription Factors
KW - Genes, Mitochondrial
KW - Glucose
KW - Lipids
KW - Male
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Muscle, Skeletal
KW - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
KW - Physical Conditioning, Animal
KW - Signal Transduction
KW - Sirtuin 1
KW - Trans-Activators
KW - Transcription Factors
KW - Up-Regulation
KW - Journal Article
KW - Research Support, N.I.H., Extramural
KW - Research Support, Non-U.S. Gov't
U2 - 10.1016/j.cmet.2010.02.006
DO - 10.1016/j.cmet.2010.02.006
M3 - Journal article
C2 - 20197054
VL - 11
SP - 213
EP - 219
JO - Cell Metabolism
JF - Cell Metabolism
SN - 1550-4131
IS - 3
ER -
ID: 170597655