IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v429y2004i6993d10.1038_nature02583.html
   My bibliography  Save this article

Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-γ

Author

Listed:
  • Frédéric Picard

    (Massachusetts Institute of Technology)

  • Martin Kurtev

    (Massachusetts Institute of Technology)

  • Namjin Chung

    (Massachusetts Institute of Technology)

  • Acharawan Topark-Ngarm

    (College of Pharmacy and Environmental Health Science Center, Oregon State University)

  • Thanaset Senawong

    (College of Pharmacy and Environmental Health Science Center, Oregon State University)

  • Rita Machado de Oliveira

    (Massachusetts Institute of Technology
    University of Porto)

  • Mark Leid

    (College of Pharmacy and Environmental Health Science Center, Oregon State University)

  • Michael W. McBurney

    (University of Ottawa)

  • Leonard Guarente

    (Massachusetts Institute of Technology)

Abstract

Calorie restriction extends lifespan in organisms ranging from yeast to mammals1. In yeast, the SIR2 gene mediates the life-extending effects of calorie restriction2. Here we show that the mammalian SIR2 orthologue, Sirt1 (sirtuin 1), activates a critical component of calorie restriction in mammals; that is, fat mobilization in white adipocytes. Upon food withdrawal Sirt1 protein binds to and represses genes controlled by the fat regulator PPAR-γ (peroxisome proliferator-activated receptor-γ), including genes mediating fat storage. Sirt1 represses PPAR-γ by docking with its cofactors NCoR (nuclear receptor co-repressor) and SMRT (silencing mediator of retinoid and thyroid hormone receptors). Mobilization of fatty acids from white adipocytes upon fasting is compromised in Sirt1+/- mice. Repression of PPAR-γ by Sirt1 is also evident in 3T3-L1 adipocytes, where overexpression of Sirt1 attenuates adipogenesis, and RNA interference of Sirt1 enhances it. In differentiated fat cells, upregulation of Sirt1 triggers lipolysis and loss of fat. As a reduction in fat is sufficient to extend murine lifespan3, our results provide a possible molecular pathway connecting calorie restriction to life extension in mammals.

Suggested Citation

  • Frédéric Picard & Martin Kurtev & Namjin Chung & Acharawan Topark-Ngarm & Thanaset Senawong & Rita Machado de Oliveira & Mark Leid & Michael W. McBurney & Leonard Guarente, 2004. "Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-γ," Nature, Nature, vol. 429(6993), pages 771-776, June.
    • Handle: RePEc:nat:nature:v:429:y:2004:i:6993:d:10.1038_nature02583
    DOI: 10.1038/nature02583
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature02583
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/nature02583?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Kevin G Culligan, 2017. "Nampt: Intracellular and Extracellular Influence on Diabetes and Obesity," Current Research in Diabetes & Obesity Journal, Juniper Publishers Inc., vol. 4(3), pages 62-66, October.
    2. Jae Woo Park & Eun Roh & Gil Myoung Kang & So Young Gil & Hyun Kyong Kim & Chan Hee Lee & Won Hee Jang & Se Eun Park & Sang Yun Moon & Seong Jun Kim & So Yeon Jeong & Chae Beom Park & Hyo Sun Lim & Yu, 2023. "Circulating blood eNAMPT drives the circadian rhythms in locomotor activity and energy expenditure," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    3. Stefania D’Angelo & Elena Mele & Federico Di Filippo & Andrea Viggiano & Rosaria Meccariello, 2021. "Sirt1 Activity in the Brain: Simultaneous Effects on Energy Homeostasis and Reproduction," IJERPH, MDPI, vol. 18(3), pages 1-17, January.
    4. Quetzalcoatl Escalante-Covarrubias & Lucía Mendoza-Viveros & Mirna González-Suárez & Román Sitten-Olea & Laura A. Velázquez-Villegas & Fernando Becerril-Pérez & Ignacio Pacheco-Bernal & Erick Carreño-, 2023. "Time-of-day defines NAD+ efficacy to treat diet-induced metabolic disease by synchronizing the hepatic clock in mice," Nature Communications, Nature, vol. 14(1), pages 1-24, December.
    5. Bin Li, 2019. "Sirt1 Inhibits Adipose Tissue Inflammation by Foxos/ mTOR/S6K1 Signal Pathway in Mice," Biomedical Journal of Scientific & Technical Research, Biomedical Research Network+, LLC, vol. 19(5), pages 14646-14655, July.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:429:y:2004:i:6993:d:10.1038_nature02583. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.