IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v6y2015i1d10.1038_ncomms7356.html
   My bibliography  Save this article

Brown fat activation reduces hypercholesterolaemia and protects from atherosclerosis development

Author

Listed:
  • Jimmy F. P. Berbée

    (Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands
    Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands)

  • Mariëtte R Boon

    (Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands
    Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands)

  • P. Padmini S. J. Khedoe

    (Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands
    Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands
    Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands)

  • Alexander Bartelt

    (University Medical Center Hamburg-Eppendorf, Martinistraße 52
    Harvard School of Public Health, Boston, Massachusetts 02115, USA)

  • Christian Schlein

    (University Medical Center Hamburg-Eppendorf, Martinistraße 52)

  • Anna Worthmann

    (University Medical Center Hamburg-Eppendorf, Martinistraße 52)

  • Sander Kooijman

    (Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands
    Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands)

  • Geerte Hoeke

    (Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands
    Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands)

  • Isabel M. Mol

    (Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands
    Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands)

  • Clara John

    (University Medical Center Hamburg-Eppendorf, Martinistraße 52)

  • Caroline Jung

    (Diagnostic and Interventional Radiology, University Medical Center Hamburg-Eppendorf, Martinistraße 52)

  • Nadia Vazirpanah

    (Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands
    Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands)

  • Linda P.J. Brouwers

    (Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands
    Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands)

  • Philip L.S.M. Gordts

    (University of California–San Diego, La Jolla, California 92093, USA)

  • Jeffrey D. Esko

    (University of California–San Diego, La Jolla, California 92093, USA)

  • Pieter S. Hiemstra

    (Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands)

  • Louis M. Havekes

    (Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands
    Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands
    Leiden University Medical Center, Albinusdreef 2
    Netherlands Organization for Applied Scientific Research—Metabolic Health Research, Gaubius Laboratory, Zernikedreef 9)

  • Ludger Scheja

    (University Medical Center Hamburg-Eppendorf, Martinistraße 52)

  • Joerg Heeren

    (University Medical Center Hamburg-Eppendorf, Martinistraße 52)

  • Patrick C.N. Rensen

    (Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands
    Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands)

Abstract

Brown adipose tissue (BAT) combusts high amounts of fatty acids, thereby lowering plasma triglyceride levels and reducing obesity. However, the precise role of BAT in plasma cholesterol metabolism and atherosclerosis development remains unclear. Here we show that BAT activation by β3-adrenergic receptor stimulation protects from atherosclerosis in hyperlipidemic APOE*3-Leiden.CETP mice, a well-established model for human-like lipoprotein metabolism that unlike hyperlipidemic Apoe−/− and Ldlr−/− mice expresses functional apoE and LDLR. BAT activation increases energy expenditure and decreases plasma triglyceride and cholesterol levels. Mechanistically, we demonstrate that BAT activation enhances the selective uptake of fatty acids from triglyceride-rich lipoproteins into BAT, subsequently accelerating the hepatic clearance of the cholesterol-enriched remnants. These effects depend on a functional hepatic apoE-LDLR clearance pathway as BAT activation in Apoe−/− and Ldlr−/− mice does not attenuate hypercholesterolaemia and atherosclerosis. We conclude that activation of BAT is a powerful therapeutic avenue to ameliorate hyperlipidaemia and protect from atherosclerosis.

Suggested Citation

  • Jimmy F. P. Berbée & Mariëtte R Boon & P. Padmini S. J. Khedoe & Alexander Bartelt & Christian Schlein & Anna Worthmann & Sander Kooijman & Geerte Hoeke & Isabel M. Mol & Clara John & Caroline Jung & , 2015. "Brown fat activation reduces hypercholesterolaemia and protects from atherosclerosis development," Nature Communications, Nature, vol. 6(1), pages 1-11, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7356
    DOI: 10.1038/ncomms7356
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms7356
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms7356?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
    ---><---

    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:6:y:2015:i:1:d:10.1038_ncomms7356. 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.