IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v9y2018i1d10.1038_s41467-018-03998-z.html
   My bibliography  Save this article

Reduced oxidative capacity in macrophages results in systemic insulin resistance

Author

Listed:
  • Saet-Byel Jung

    (Chungnam National University)

  • Min Jeong Choi

    (Chungnam National University)

  • Dongryeol Ryu

    (École Polytechnique Fédérale de Lausanne
    Pusan National University)

  • Hyon-Seung Yi

    (Chungnam National University Hospital)

  • Seong Eun Lee

    (Chungnam National University)

  • Joon Young Chang

    (Chungnam National University)

  • Hyo Kyun Chung

    (Chungnam National University)

  • Yong Kyung Kim

    (Chungnam National University)

  • Seul Gi Kang

    (Chungnam National University)

  • Ju Hee Lee

    (Chungnam National University Hospital)

  • Koon Soon Kim

    (Chungnam National University
    Chungnam National University Hospital)

  • Hyun Jin Kim

    (Chungnam National University Hospital)

  • Cuk-Seong Kim

    (Chungnam National University)

  • Chul-Ho Lee

    (Korea Research Institute of Bioscience and Biotechnology)

  • Robert W. Williams

    (University of Tennessee Health Science Center)

  • Hail Kim

    (Korea Advanced Institute of Science and Technology)

  • Heung Kyu Lee

    (Korea Advanced Institute of Science and Technology)

  • Johan Auwerx

    (École Polytechnique Fédérale de Lausanne)

  • Minho Shong

    (Chungnam National University
    Chungnam National University Hospital)

Abstract

Oxidative functions of adipose tissue macrophages control the polarization of M1-like and M2-like phenotypes, but whether reduced macrophage oxidative function causes systemic insulin resistance in vivo is not clear. Here, we show that mice with reduced mitochondrial oxidative phosphorylation (OxPhos) due to myeloid-specific deletion of CR6-interacting factor 1 (Crif1), an essential mitoribosomal factor involved in biogenesis of OxPhos subunits, have M1-like polarization of macrophages and systemic insulin resistance with adipose inflammation. Macrophage GDF15 expression is reduced in mice with impaired oxidative function, but induced upon stimulation with rosiglitazone and IL-4. GDF15 upregulates the oxidative function of macrophages, leading to M2-like polarization, and reverses insulin resistance in ob/ob mice and HFD-fed mice with myeloid-specific deletion of Crif1. Thus, reduced macrophage oxidative function controls systemic insulin resistance and adipose inflammation, which can be reversed with GDF15 and leads to improved oxidative function of macrophages.

Suggested Citation

  • Saet-Byel Jung & Min Jeong Choi & Dongryeol Ryu & Hyon-Seung Yi & Seong Eun Lee & Joon Young Chang & Hyo Kyun Chung & Yong Kyung Kim & Seul Gi Kang & Ju Hee Lee & Koon Soon Kim & Hyun Jin Kim & Cuk-Se, 2018. "Reduced oxidative capacity in macrophages results in systemic insulin resistance," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03998-z
    DOI: 10.1038/s41467-018-03998-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-03998-z
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-018-03998-z?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. Shaojian Lin & Anke Zhang & Ling Yuan & Yufan Wang & Chuan Zhang & Junkun Jiang & Houshi Xu & Huiwen Yuan & Hui Yao & Qianying Zhang & Yong Zhang & Meiqing Lou & Ping Wang & Zhen-Ning Zhang & Bing Lua, 2022. "Targeting parvalbumin promotes M2 macrophage polarization and energy expenditure in mice," Nature Communications, Nature, vol. 13(1), pages 1-15, 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:9:y:2018:i:1:d:10.1038_s41467-018-03998-z. 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.