Interdependence of AMPK and SIRT1 for metabolic adaptation to fasting and exercise in skeletal muscle

Carles Cantó; Lake Q Jiang; Atul S Deshmukh; Chikage Mataki; Agnes Coste; Marie Lagouge; Juleen R Zierath; Johan Auwerx

doi:10.1016/j.cmet.2010.02.006

Interdependence of AMPK and SIRT1 for metabolic adaptation to fasting and exercise in skeletal muscle

Carles Cantó, Lake Q Jiang, Atul S Deshmukh, Chikage Mataki, Agnes Coste, Marie Lagouge, Juleen R Zierath, Johan Auwerx

575 Citationer (Scopus)

Abstract

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-1α 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-1α 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.

Originalsprog	Engelsk
Tidsskrift	Cell Metabolism
Vol/bind	11
Udgave nummer	3
Sider (fra-til)	213-9
Antal sider	7
ISSN	1550-4131
DOI	https://doi.org/10.1016/j.cmet.2010.02.006
Status	Udgivet - 3 mar. 2010

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10.1016/j.cmet.2010.02.006

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title = "Interdependence of AMPK and SIRT1 for metabolic adaptation to fasting and exercise in skeletal muscle",

abstract = "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-1α 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-1α 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.",

keywords = "AMP-Activated Protein Kinases, Animals, Cells, Cultured, Energy Metabolism, Fasting, Forkhead Box Protein O1, Forkhead Transcription Factors, Genes, Mitochondrial, Glucose, Lipids, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Muscle, Skeletal, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Physical Conditioning, Animal, Signal Transduction, Sirtuin 1, Trans-Activators, Transcription Factors, Up-Regulation, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't",

author = "Carles Cant{\'o} and Jiang, {Lake Q} and Deshmukh, {Atul S} and Chikage Mataki and Agnes Coste and Marie Lagouge and Zierath, {Juleen R} and Johan Auwerx",

year = "2010",

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doi = "10.1016/j.cmet.2010.02.006",

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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

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-1α 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-1α 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-1α 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-1α 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

SN - 1550-4131

VL - 11

SP - 213

EP - 219

JO - Cell Metabolism

JF - Cell Metabolism

IS - 3

ER -

Interdependence of AMPK and SIRT1 for metabolic adaptation to fasting and exercise in skeletal muscle

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