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-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 mitoch

SUBMITTER: Canto C 

PROVIDER: S-EPMC3616265 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature