AMPK regulates energy expenditure by modulating NAD + metabolism and SIRT1 activity

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AMPK regulates energy expenditure by modulating NAD + metabolism and SIRT1 activity. / Cantó, Carles; Gerhart-Hines, Zachary; Feige, Jerome N.; Lagouge, Marie; Noriega, Lilia; Milne, Jill C.; Elliott, Peter J.; Puigserver, Pere; Auwerx, Johan.

In: Nature, Vol. 458, No. 7241, 23.04.2009, p. 1056-1060.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Cantó, C, Gerhart-Hines, Z, Feige, JN, Lagouge, M, Noriega, L, Milne, JC, Elliott, PJ, Puigserver, P & Auwerx, J 2009, 'AMPK regulates energy expenditure by modulating NAD + metabolism and SIRT1 activity', Nature, vol. 458, no. 7241, pp. 1056-1060. https://doi.org/10.1038/nature07813

APA

Cantó, C., Gerhart-Hines, Z., Feige, J. N., Lagouge, M., Noriega, L., Milne, J. C., Elliott, P. J., Puigserver, P., & Auwerx, J. (2009). AMPK regulates energy expenditure by modulating NAD + metabolism and SIRT1 activity. Nature, 458(7241), 1056-1060. https://doi.org/10.1038/nature07813

Vancouver

Cantó C, Gerhart-Hines Z, Feige JN, Lagouge M, Noriega L, Milne JC et al. AMPK regulates energy expenditure by modulating NAD + metabolism and SIRT1 activity. Nature. 2009 Apr 23;458(7241):1056-1060. https://doi.org/10.1038/nature07813

Author

Cantó, Carles ; Gerhart-Hines, Zachary ; Feige, Jerome N. ; Lagouge, Marie ; Noriega, Lilia ; Milne, Jill C. ; Elliott, Peter J. ; Puigserver, Pere ; Auwerx, Johan. / AMPK regulates energy expenditure by modulating NAD + metabolism and SIRT1 activity. In: Nature. 2009 ; Vol. 458, No. 7241. pp. 1056-1060.

Bibtex

@article{8eb3e1becb784bf58621d802b381965c,
title = "AMPK regulates energy expenditure by modulating NAD + metabolism and SIRT1 activity",
abstract = "AMP-activated protein kinase (AMPK) is a metabolic fuel gauge conserved along the evolutionary scale in eukaryotes that senses changes in the intracellular AMP/ATP ratio. Recent evidence indicated an important role for AMPK in the therapeutic benefits of metformin, thiazolidinediones and exercise, which form the cornerstones of the clinical management of type 2 diabetes and associated metabolic disorders. In general, activation of AMPK acts to maintain cellular energy stores, switching on catabolic pathways that produce ATP, mostly by enhancing oxidative metabolism and mitochondrial biogenesis, while switching off anabolic pathways that consume ATP. This regulation can take place acutely, through the regulation of fast post-translational events, but also by transcriptionally reprogramming the cell to meet energetic needs. Here we demonstrate that AMPK controls the expression of genes involved in energy metabolism in mouse skeletal muscle by acting in coordination with another metabolic sensor, the NAD + -dependent type III deacetylase SIRT1. AMPK enhances SIRT1 activity by increasing cellular NAD + levels, resulting in the deacetylation and modulation of the activity of downstream SIRT1 targets that include the peroxisome proliferator-activated receptor-γ coactivator 1α and the forkhead box O1 (FOXO1) and O3 (FOXO3a) transcription factors. The AMPK-induced SIRT1-mediated deacetylation of these targets explains many of the convergent biological effects of AMPK and SIRT1 on energy metabolism.",
author = "Carles Cant{\'o} and Zachary Gerhart-Hines and Feige, {Jerome N.} and Marie Lagouge and Lilia Noriega and Milne, {Jill C.} and Elliott, {Peter J.} and Pere Puigserver and Johan Auwerx",
note = "Funding Information: Acknowledgements This work was supported by grants of CNRS, Ecole Polytechnique F{\'e}d{\'e}rale de Lausanne, INSERM, ULP, NIH (DK59820 and DK069966), EU FP6 (EUGENE2; LSHM-CT-2004-512013) and EU Ideas programme (sirtuins; ERC-2008-AdG-23118). C.C. has been supported by grants of Fondation de la Recherche Medicale (FRM) and EMBO. J.N.F. was supported by a FEBS grant. The authors thank F. Foufelle and P. Ferre, B. Spiegelman, D. P. Kelly, S.-i. Imai, G. Hardie, C. Ammann (Topotarget) and F. Alt for providing materials, and members of the Auwerx and Puigserver laboratories for discussion.",
year = "2009",
month = apr,
day = "23",
doi = "10.1038/nature07813",
language = "English",
volume = "458",
pages = "1056--1060",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "nature publishing group",
number = "7241",

}

RIS

TY - JOUR

T1 - AMPK regulates energy expenditure by modulating NAD + metabolism and SIRT1 activity

AU - Cantó, Carles

AU - Gerhart-Hines, Zachary

AU - Feige, Jerome N.

AU - Lagouge, Marie

AU - Noriega, Lilia

AU - Milne, Jill C.

AU - Elliott, Peter J.

AU - Puigserver, Pere

AU - Auwerx, Johan

N1 - Funding Information: Acknowledgements This work was supported by grants of CNRS, Ecole Polytechnique Fédérale de Lausanne, INSERM, ULP, NIH (DK59820 and DK069966), EU FP6 (EUGENE2; LSHM-CT-2004-512013) and EU Ideas programme (sirtuins; ERC-2008-AdG-23118). C.C. has been supported by grants of Fondation de la Recherche Medicale (FRM) and EMBO. J.N.F. was supported by a FEBS grant. The authors thank F. Foufelle and P. Ferre, B. Spiegelman, D. P. Kelly, S.-i. Imai, G. Hardie, C. Ammann (Topotarget) and F. Alt for providing materials, and members of the Auwerx and Puigserver laboratories for discussion.

PY - 2009/4/23

Y1 - 2009/4/23

N2 - AMP-activated protein kinase (AMPK) is a metabolic fuel gauge conserved along the evolutionary scale in eukaryotes that senses changes in the intracellular AMP/ATP ratio. Recent evidence indicated an important role for AMPK in the therapeutic benefits of metformin, thiazolidinediones and exercise, which form the cornerstones of the clinical management of type 2 diabetes and associated metabolic disorders. In general, activation of AMPK acts to maintain cellular energy stores, switching on catabolic pathways that produce ATP, mostly by enhancing oxidative metabolism and mitochondrial biogenesis, while switching off anabolic pathways that consume ATP. This regulation can take place acutely, through the regulation of fast post-translational events, but also by transcriptionally reprogramming the cell to meet energetic needs. Here we demonstrate that AMPK controls the expression of genes involved in energy metabolism in mouse skeletal muscle by acting in coordination with another metabolic sensor, the NAD + -dependent type III deacetylase SIRT1. AMPK enhances SIRT1 activity by increasing cellular NAD + levels, resulting in the deacetylation and modulation of the activity of downstream SIRT1 targets that include the peroxisome proliferator-activated receptor-γ coactivator 1α and the forkhead box O1 (FOXO1) and O3 (FOXO3a) transcription factors. The AMPK-induced SIRT1-mediated deacetylation of these targets explains many of the convergent biological effects of AMPK and SIRT1 on energy metabolism.

AB - AMP-activated protein kinase (AMPK) is a metabolic fuel gauge conserved along the evolutionary scale in eukaryotes that senses changes in the intracellular AMP/ATP ratio. Recent evidence indicated an important role for AMPK in the therapeutic benefits of metformin, thiazolidinediones and exercise, which form the cornerstones of the clinical management of type 2 diabetes and associated metabolic disorders. In general, activation of AMPK acts to maintain cellular energy stores, switching on catabolic pathways that produce ATP, mostly by enhancing oxidative metabolism and mitochondrial biogenesis, while switching off anabolic pathways that consume ATP. This regulation can take place acutely, through the regulation of fast post-translational events, but also by transcriptionally reprogramming the cell to meet energetic needs. Here we demonstrate that AMPK controls the expression of genes involved in energy metabolism in mouse skeletal muscle by acting in coordination with another metabolic sensor, the NAD + -dependent type III deacetylase SIRT1. AMPK enhances SIRT1 activity by increasing cellular NAD + levels, resulting in the deacetylation and modulation of the activity of downstream SIRT1 targets that include the peroxisome proliferator-activated receptor-γ coactivator 1α and the forkhead box O1 (FOXO1) and O3 (FOXO3a) transcription factors. The AMPK-induced SIRT1-mediated deacetylation of these targets explains many of the convergent biological effects of AMPK and SIRT1 on energy metabolism.

UR - http://www.scopus.com/inward/record.url?scp=67349276169&partnerID=8YFLogxK

U2 - 10.1038/nature07813

DO - 10.1038/nature07813

M3 - Journal article

C2 - 19262508

AN - SCOPUS:67349276169

VL - 458

SP - 1056

EP - 1060

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 7241

ER -

ID: 347795141