IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v7y2016i1d10.1038_ncomms11365.html
   My bibliography  Save this article

Adipose tissue mTORC2 regulates ChREBP-driven de novo lipogenesis and hepatic glucose metabolism

Author

Listed:
  • Yuefeng Tang

    (Program in Molecular Medicine, University of Massachusetts Medical School)

  • Martina Wallace

    (University of California, San Diego)

  • Joan Sanchez-Gurmaches

    (Program in Molecular Medicine, University of Massachusetts Medical School)

  • Wen-Yu Hsiao

    (Program in Molecular Medicine, University of Massachusetts Medical School)

  • Huawei Li

    (Program in Molecular Medicine, University of Massachusetts Medical School)

  • Peter L. Lee

    (Program in Molecular Medicine, University of Massachusetts Medical School)

  • Santiago Vernia

    (Program in Molecular Medicine, University of Massachusetts Medical School
    Present address: Genes and Metabolism section, MRC Clinical Sciences Centre, Imperial College London, Hammersmith Campus, London W12 0NN, UK)

  • Christian M. Metallo

    (University of California, San Diego)

  • David A. Guertin

    (Program in Molecular Medicine, University of Massachusetts Medical School)

Abstract

Adipose tissue de novo lipogenesis (DNL) positively influences insulin sensitivity, is reduced in obesity, and predicts insulin resistance. Therefore, elucidating mechanisms controlling adipose tissue DNL could lead to therapies for type 2 diabetes. Here, we report that mechanistic target of rapamycin complex 2 (mTORC2) functions in white adipose tissue (WAT) to control expression of the lipogenic transcription factor ChREBPβ. Conditionally deleting the essential mTORC2 subunit Rictor in mature adipocytes decreases ChREBPβ expression, which reduces DNL in WAT, and impairs hepatic insulin sensitivity. Mechanistically, Rictor/mTORC2 promotes ChREBPβ expression in part by controlling glucose uptake, but without impairing pan-AKT signalling. High-fat diet also rapidly decreases adipose tissue ChREBPβ expression and insulin sensitivity in wild-type mice, and does not further exacerbate insulin resistance in adipose tissue Rictor knockout mice, implicating adipose tissue DNL as an early target in diet-induced insulin resistance. These data suggest mTORC2 functions in WAT as part of an extra-hepatic nutrient-sensing mechanism to control glucose homeostasis.

Suggested Citation

  • Yuefeng Tang & Martina Wallace & Joan Sanchez-Gurmaches & Wen-Yu Hsiao & Huawei Li & Peter L. Lee & Santiago Vernia & Christian M. Metallo & David A. Guertin, 2016. "Adipose tissue mTORC2 regulates ChREBP-driven de novo lipogenesis and hepatic glucose metabolism," Nature Communications, Nature, vol. 7(1), pages 1-14, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11365
    DOI: 10.1038/ncomms11365
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms11365
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms11365?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
    ---><---

    Citations

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


    Cited by:

    1. Alexander J. Hu & Wei Li & Calvin Dinh & Yongzhao Zhang & Jamie K. Hu & Stefano G. Daniele & Xiaoli Hou & Zixuan Yang & John M. Asara & Guo-fu Hu & Stephen R. Farmer & Miaofen G. Hu, 2024. "CDK6 inhibits de novo lipogenesis in white adipose tissues but not in the liver," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. 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.

    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:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11365. 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.