IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v4y2013i1d10.1038_ncomms3384.html

Microbiome remodelling leads to inhibition of intestinal farnesoid X receptor signalling and decreased obesity

Author

Listed:
  • Fei Li

    (Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

  • Changtao Jiang

    (Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

  • Kristopher W. Krausz

    (Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

  • Yunfei Li

    (Bioinformatics Consulting Center, The Pennsylvania State University)

  • Istvan Albert

    (Bioinformatics Consulting Center, The Pennsylvania State University)

  • Haiping Hao

    (Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

  • Kristin M. Fabre

    (Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

  • James B. Mitchell

    (Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

  • Andrew D. Patterson

    (Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health
    The Pennsylvania State University)

  • Frank J. Gonzalez

    (Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

Abstract

The antioxidant tempol reduces obesity in mice. Here we show that tempol alters the gut microbiome by preferentially reducing the genus Lactobacillus and its bile salt hydrolase (BSH) activity leading to the accumulation of intestinal tauro-β-muricholic acid (T-β-MCA). T-β-MCA is an farnesoid X receptor (FXR) nuclear receptor antagonist, which is involved in the regulation of bile acid, lipid and glucose metabolism. Its increased levels during tempol treatment inhibit FXR signalling in the intestine. High-fat diet-fed intestine-specific Fxr-null (FxrΔIE) mice show lower diet-induced obesity, similar to tempol-treated wild-type mice. Further, tempol treatment does not decrease weight gain in FxrΔIE mice, suggesting that the intestinal FXR mediates the anti-obesity effects of tempol. These studies demonstrate a biochemical link between the microbiome, nuclear receptor signalling and metabolic disorders, and suggest that inhibition of FXR in the intestine could be a target for anti-obesity drugs.

Suggested Citation

  • Fei Li & Changtao Jiang & Kristopher W. Krausz & Yunfei Li & Istvan Albert & Haiping Hao & Kristin M. Fabre & James B. Mitchell & Andrew D. Patterson & Frank J. Gonzalez, 2013. "Microbiome remodelling leads to inhibition of intestinal farnesoid X receptor signalling and decreased obesity," Nature Communications, Nature, vol. 4(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3384
    DOI: 10.1038/ncomms3384
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms3384
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms3384?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. Xunjiang Wang & Xu Wang & Shenglan Yu & Luyao Huang & Qiongwen Xue & Xinru Yang & Zixuan Wang & Wenyuan Lin & Yaping Jiang & Ying Xu & Qi Liao & Lihua Jin & Zhengtao Wang & Feng Tao & Li Yang & Wendon, 2026. "Schisantherin A interacts with gut bacteria to stimulate adipose tissue thermogenesis in obese mice via a TGR5‒p-CREB‒STAT6 signaling pathway," Nature Communications, Nature, vol. 17(1), pages 1-19, December.
    2. Michael DiMarzio & Brigida Rusconi & Neela H Yennawar & Mark Eppinger & Andrew D Patterson & Edward G Dudley, 2017. "Identification of a mouse Lactobacillus johnsonii strain with deconjugase activity against the FXR antagonist T-β-MCA," PLOS ONE, Public Library of Science, vol. 12(9), pages 1-15, September.
    3. Qi Zhao & Man-Yun Dai & Ruo-Yue Huang & Jing-Yi Duan & Ting Zhang & Wei-Min Bao & Jing-Yi Zhang & Shao-Qiang Gui & Shu-Min Xia & Cong-Ting Dai & Ying-Mei Tang & Frank J. Gonzalez & Fei Li, 2023. "Parabacteroides distasonis ameliorates hepatic fibrosis potentially via modulating intestinal bile acid metabolism and hepatocyte pyroptosis in male mice," Nature Communications, Nature, vol. 14(1), pages 1-18, 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:4:y:2013:i:1:d:10.1038_ncomms3384. 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.