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

By C. Cantó, Lake Q. Jiang, A. Deshmukh, C. Mataki, Agnès Coste, Marie Lagouge, J. Zierath, Johan Auwerx. Cell Metabolism, 2010

919 citations recorded by the source corpus.

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 signalling pathways are improperly triggered in AMPK deficient states.

Subfields: Geriatrics and Gerontology, Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/2a19180d075c5a5c8568675846331d5ac503852b

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Citations in the corpus

Resveratrol Ameliorates Aging-Related Metabolic Phenotypes by Inhibiting cAMP Phosphodiesterases (2012, positive): “These findings demonstrated that activation of Sirt1 and PGC-1α by resveratrol is downstream of AMPK activation.”
Nicotinamide mononucleotide, a key NAD+ intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice (2011, background): “528 Cell Metabolism 14, 528–536, October 5, 2011 a2011 Elsevier In For example, in skeletal muscle, both nutritional deprivation and exercise increase Nampt expression through the activation of AMP-activated protein kinase (AMPK), thereby enhancing NAD biosynthesis and SIRT1 activity (Cantó et al., ”
NAD+ metabolism and the control of energy homeostasis - a balancing act between mitochondria and the nucleus (2015, background): “For example, SIRT1 activity increases during exercise (Cantó et al., 2009), CR (Chen et al., 2008), fasting (Cantó et al., 2010; Rodgers et al., 2005), or low glucose availability (Fulco et al., 2008), all of which correlate with higher NAD+ levels.”
PARP-1 inhibition increases mitochondrial metabolism through SIRT1 activation (2011, positive): “Nutrient scarcity and AMPK activation also lead to increased NAD+ levels and SIRT1 activation coupled to the induction of oxidative metabolism (Cantó et al., 2009, 2010).”
Calorie restriction-like effects of 30 days of Resveratrol (resVida™) supplementation on energy metabolism and metabolic profile in obese humans (2011, background): “…SIRT1 directly (Beher et al., 2009; Pacholec et al., 2010), but rather exerts its effects on SIRT1 through activation of AMPK (Baur et al., 2006; Cantó et al., 2009, 2010; Feige et al., 2008; Hawley et al., 2010; Um et al., 2010), although additional direct SIRT1 activation is not completely…”
NAD+ metabolism: pathophysiologic mechanisms and therapeutic potential (2020, background): “The exercise-mediated NAD boosting by inducing Nampt is a response strategy for energy stress, which is abolished by depletion of the energy sensor AMPK.(603) Intriguingly, the gut microenvironment, especially the host-bacteria interactions also contributes to NAD metabolism.”
Autophagy and aging. (2011, background): “…reduced intake, its onset (juvenile versus adult), or its intensity—CR induces autophagy through the activation of either of two energy sensors, AMPK (Egan et al., 2011; Kim et al., 2011) and Sirtuin 1 (SIRT1), which engage in a positive forward loop of mutual activation (Cantó et al., 2010).”
AMP-activated protein kinase: an energy sensor that regulates all aspects of cell function. (2011, background): “An alternative mechanism by which AMPK may activate PGC-1a function is by deacetylation catalyzed by the NAD-dependent deacetylase SIRT1 (Canto et al. 2010), although the exact mechanism by which AMPK activates SIRT1 remains uncertain.”
Mitochondria: In Sickness and in Health (2012, background): “…nutrient oxidation, and ATP production to fit a cell’s particular needs via the transcription cofactor, peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1a) (Cantó et al., 2009, 2010; Jäger et al., 2007; Jeninga et al., 2010; Puigserver et al., 1998; Wu et al., 1999).”