Interdependence of AMPK and SIRT1 for Metabolic Adaptation to Fasting and Exercise in Skeletal Muscle

被引：762

作者：

Canto, Carles ^{[1
]}

Jiang, Lake Q. ^{[2
]}

Deshmukh, Atul S. ^{[2
]}

Mataki, Chikage ^{[1
]}

Coste, Agnes ^{[3
]}

Lagouge, Marie ^{[3
]}

Zierath, Juleen R. ^{[2
]}

Auwerx, Johan ^{[1
]}

机构：

[1] Ecole Polytech Fed Lausanne, CH-1015 Lausanne, Switzerland

[2] Karolinska Inst, Dept Mol Med & Surg, S-17177 Stockholm, Sweden

[3] Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch Graffenstaden, France

来源：

CELL METABOLISM | 2010年 / 11卷 / 03期

基金：

瑞典研究理事会; 美国国家卫生研究院; 瑞士国家科学基金会; 欧洲研究理事会;

关键词：

ACTIVATED PROTEIN-KINASE; GLUCOSE-HOMEOSTASIS; ENERGY-EXPENDITURE; LIPID-METABOLISM; GENE-EXPRESSION; LIFE-SPAN; PGC-1-ALPHA; GAMMA-3; DEPRIVATION; TRANSPORT;

D O I：

10.1016/j.cmet.2010.02.006

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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-1 alpha 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-1 alpha 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.

引用

页码：213 / 219

页数：7