IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v434y2005i7029d10.1038_nature03354.html
   My bibliography  Save this article

Nutrient control of glucose homeostasis through a complex of PGC-1α and SIRT1

Author

Listed:
  • Joseph T. Rodgers

    (Johns Hopkins University School of Medicine)

  • Carlos Lerin

    (Johns Hopkins University School of Medicine)

  • Wilhelm Haas

    (Harvard Medical School)

  • Steven P. Gygi

    (Harvard Medical School)

  • Bruce M. Spiegelman

    (Harvard Medical School
    Harvard Medical School)

  • Pere Puigserver

    (Johns Hopkins University School of Medicine)

Abstract

Homeostatic mechanisms in mammals respond to hormones and nutrients to maintain blood glucose levels within a narrow range. Caloric restriction causes many changes in glucose metabolism and extends lifespan; however, how this metabolism is connected to the ageing process is largely unknown. We show here that the Sir2 homologue, SIRT1—which modulates ageing in several species1,2,3 —controls the gluconeogenic/glycolytic pathways in liver in response to fasting signals through the transcriptional coactivator PGC-1α. A nutrient signalling response that is mediated by pyruvate induces SIRT1 protein in liver during fasting. We find that once SIRT1 is induced, it interacts with and deacetylates PGC-1α at specific lysine residues in an NAD+-dependent manner. SIRT1 induces gluconeogenic genes and hepatic glucose output through PGC-1α, but does not regulate the effects of PGC-1α on mitochondrial genes. In addition, SIRT1 modulates the effects of PGC-1α repression of glycolytic genes in response to fasting and pyruvate. Thus, we have identified a molecular mechanism whereby SIRT1 functions in glucose homeostasis as a modulator of PGC-1α. These findings have strong implications for the basic pathways of energy homeostasis, diabetes and lifespan.

Suggested Citation

  • Joseph T. Rodgers & Carlos Lerin & Wilhelm Haas & Steven P. Gygi & Bruce M. Spiegelman & Pere Puigserver, 2005. "Nutrient control of glucose homeostasis through a complex of PGC-1α and SIRT1," Nature, Nature, vol. 434(7029), pages 113-118, March.
    • Handle: RePEc:nat:nature:v:434:y:2005:i:7029:d:10.1038_nature03354
    DOI: 10.1038/nature03354
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature03354
    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/nature03354?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. 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.
    2. Simeon R. Mihaylov & Lydia M. Castelli & Ya-Hui Lin & Aytac Gül & Nikita Soni & Christopher Hastings & Helen R. Flynn & Oana Păun & Mark J. Dickman & Ambrosius P. Snijders & Robert Goldstone & Oliver, 2023. "The master energy homeostasis regulator PGC-1α exhibits an mRNA nuclear export function," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    3. Yoona Kim & Peter Clifton, 2018. "Curcumin, Cardiometabolic Health and Dementia," IJERPH, MDPI, vol. 15(10), pages 1-34, September.
    4. Guanlan Hu & Catriona Ling & Lijun Chi & Mehakpreet K. Thind & Samuel Furse & Albert Koulman & Jonathan R. Swann & Dorothy Lee & Marjolein M. Calon & Celine Bourdon & Christian J. Versloot & Barbara M, 2022. "The role of the tryptophan-NAD + pathway in a mouse model of severe malnutrition induced liver dysfunction," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    5. Kanwar Abhay Singh & John Soukar & Mohammad Zulkifli & Anna Kersey & Giriraj Lokhande & Sagnika Ghosh & Aparna Murali & Natalie M. Garza & Harman Kaur & Justin N. Keeney & Ramu Banavath & Hatice Ceyla, 2024. "Atomic vacancies of molybdenum disulfide nanoparticles stimulate mitochondrial biogenesis," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    6. Liang Yang & Junfeng Shen & Chunhua Liu & Zhonghua Kuang & Yong Tang & Zhengjiang Qian & Min Guan & Yongfeng Yang & Yang Zhan & Nan Li & Xiang Li, 2023. "Nicotine rebalances NAD+ homeostasis and improves aging-related symptoms in male mice by enhancing NAMPT activity," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

    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:434:y:2005:i:7029:d:10.1038_nature03354. 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.