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

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  • Carles Cantó

    (Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, 67404 Illkirch, France
    Ecole Polytechnique Fédérale de Lausanne)

  • Zachary Gerhart-Hines

    (Harvard Medical School, Boston, Massachusetts 02115, USA)

  • Jerome N. Feige

    (Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, 67404 Illkirch, France)

  • Marie Lagouge

    (Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, 67404 Illkirch, France)

  • Lilia Noriega

    (Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, 67404 Illkirch, France
    Ecole Polytechnique Fédérale de Lausanne)

  • Jill C. Milne

    (Sirtris Pharmaceuticals Inc., Cambridge, Massachusetts 02139, USA)

  • Peter J. Elliott

    (Sirtris Pharmaceuticals Inc., Cambridge, Massachusetts 02139, USA)

  • Pere Puigserver

    (Harvard Medical School, Boston, Massachusetts 02115, USA)

  • Johan Auwerx

    (Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, 67404 Illkirch, France
    Ecole Polytechnique Fédérale de Lausanne
    Institut Clinique de la Souris, BP10142, 67404 Illkirch, France)

Abstract

Energy metabolism AMP-activated protein kinase (AMPK) is a cellular energy sensor that helps coordinate glucose and lipid metabolism. Here, AMPK is shown to transcriptionally regulate genes involved in controlling energy metabolism in skeletal muscle by acting together with the NAD+-dependent deacetylase SIRT1. AMPK enhances SIRT1 activity by increasing cellular NAD+ levels. This results in the deacetylation and activation of the SIRT1 downstream target PGC-1α.

Suggested Citation

  • Carles Cantó & Zachary Gerhart-Hines & Jerome N. Feige & Marie Lagouge & Lilia Noriega & Jill C. Milne & Peter J. Elliott & Pere Puigserver & Johan Auwerx, 2009. "AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity," Nature, Nature, vol. 458(7241), pages 1056-1060, April.
    • Handle: RePEc:nat:nature:v:458:y:2009:i:7241:d:10.1038_nature07813
    DOI: 10.1038/nature07813
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    Cited by:

    1. Yuanpei Li & Xiaoniu He & Xiao Lu & Zhicheng Gong & Qing Li & Lei Zhang & Ronghui Yang & Chengyi Wu & Jialiang Huang & Jiancheng Ding & Yaohui He & Wen Liu & Ceshi Chen & Bin Cao & Dawang Zhou & Yufen, 2022. "METTL3 acetylation impedes cancer metastasis via fine-tuning its nuclear and cytosolic functions," Nature Communications, Nature, vol. 13(1), pages 1-23, December.
    2. Nadège Zanou & Haikel Dridi & Steven Reiken & Tanes Imamura de Lima & Chris Donnelly & Umberto De Marchi & Manuele Ferrini & Jeremy Vidal & Leah Sittenfeld & Jerome N. Feige & Pablo M. Garcia-Roves & , 2021. "Acute RyR1 Ca2+ leak enhances NADH-linked mitochondrial respiratory capacity," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    3. Aurore Claude-Taupin & Pierre Isnard & Alessia Bagattin & Nicolas Kuperwasser & Federica Roccio & Biagina Ruscica & Nicolas Goudin & Meriem Garfa-Traoré & Alice Regnier & Lisa Turinsky & Martine Burti, 2023. "The AMPK-Sirtuin 1-YAP axis is regulated by fluid flow intensity and controls autophagy flux in kidney epithelial cells," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    4. Jia Luo & Changfa Tang & Xiaobin Chen & Zhanbing Ren & Honglin Qu & Rong Chen & Zhen Tong, 2020. "Impacts of Aerobic Exercise on Depression-Like Behaviors in Chronic Unpredictable Mild Stress Mice and Related Factors in the AMPK/PGC-1α Pathway," IJERPH, MDPI, vol. 17(6), pages 1-12, March.
    5. Joan Serrano & Jordan Boyd & Ian S. Brown & Carter Mason & Kathleen R. Smith & Katalin Karolyi & Santosh K. Maurya & Nishita N. Meshram & Vanida Serna & Grace M. Link & Stephen J. Gardell & George A. , 2024. "The TAS1R2 G-protein-coupled receptor is an ambient glucose sensor in skeletal muscle that regulates NAD homeostasis and mitochondrial capacity," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    6. Su-Youn Cho & Young-Soo Chung & Hyoung-Ki Yoon & Hee-Tae Roh, 2022. "Impact of Exercise Intensity on Systemic Oxidative Stress, Inflammatory Responses, and Sirtuin Levels in Healthy Male Volunteers," IJERPH, MDPI, vol. 19(18), pages 1-9, September.
    7. Yi-Fang Cheng & Guang-Huar Young & Jiun-Tsai Lin & Hyun-Hwa Jang & Chin-Chen Chen & Jing-Yi Nong & Po-Ku Chen & Cheng-Yi Kuo & Shao-Hsuan Kao & Yao-Jen Liang & Han-Min Chen, 2015. "Activation of AMP-Activated Protein Kinase by Adenine Alleviates TNF-Alpha-Induced Inflammation in Human Umbilical Vein Endothelial Cells," PLOS ONE, Public Library of Science, vol. 10(11), pages 1-14, November.
    8. Éverton Lopes Vogt & Maiza Cristina Von Dentz & Débora Santos Rocha & Jorge Felipe Argenta Model & Lucas Stahlhöfer Kowalewski & Samir Khal de Souza & Vitória de Oliveira Girelli & Paulo Ivo Homem de , 2021. "Metabolic and Molecular Subacute Effects of a Single Moderate-Intensity Exercise Bout, Performed in the Fasted State, in Obese Male Rats," IJERPH, MDPI, vol. 18(14), pages 1-17, July.
    9. Weiwei Liu & Hao Zhou & Han Wang & Quanri Zhang & Renliang Zhang & Belinda Willard & Caini Liu & Zizhen Kang & Xiao Li & Xiaoxia Li, 2022. "IL-1R-IRAKM-Slc25a1 signaling axis reprograms lipogenesis in adipocytes to promote diet-induced obesity in mice," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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