1. Stem Cells and Regenerative Medicine

ANGPTL4 mediates shuttling of lipid fuel to brown adipose tissue during sustained cold exposure

  1. Wieneke Dijk
  2. Markus Heine
  3. Laurent Vergnes
  4. Mariëtte R Boon
  5. Gert Schaart
  6. Matthijs KC Hesselink
  7. Karen Reue
  8. Wouter D van Marken Lichtenbelt
  9. Gunilla Olivecrona
  10. Patrick CN Rensen
  11. Joerg Heeren
  12. Sander Kersten  Is a corresponding author
  1. Wageningen University, Netherlands
  2. University of Hamburg, Germany
  3. University of California, Los Angeles, United States
  4. Leiden University, Netherlands
  5. Maastricht University, Netherlands
  6. European Society for Medical Oncology, Netherlands
  7. Umeå University, Sweden
  8. Leiden University Medical Center, Netherlands
https://doi.org/10.7554/eLife.08428
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  1. Wieneke Dijk
  2. Markus Heine
  3. Laurent Vergnes
  4. Mariëtte R Boon
  5. Gert Schaart
  6. Matthijs KC Hesselink
  7. Karen Reue
  8. Wouter D van Marken Lichtenbelt
  9. Gunilla Olivecrona
  10. Patrick CN Rensen
  11. Joerg Heeren
  12. Sander Kersten
(2015)
ANGPTL4 mediates shuttling of lipid fuel to brown adipose tissue during sustained cold exposure
eLife 4:e08428.
https://doi.org/10.7554/eLife.08428
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  3. Download .RIS

Abstract

Brown adipose tissue (BAT) activation via cold exposure is increasingly scrutinized as a potential approach to ameliorate cardio-metabolic risk. Transition to cold temperatures requires changes in the partitioning of energy substrates, re-routing fatty acids to BAT to fuel non-shivering thermogenesis. However, the mechanisms behind the redistribution of energy substrates to BAT remain largely unknown. Angiopoietin-like 4 (ANGPTL4), a protein that inhibits lipoprotein lipase (LPL) activity, is highly expressed in BAT. Here, we demonstrate that ANGPTL4 is part of a shuttling mechanism that directs fatty acids derived from circulating triglyceride-rich lipoproteins to BAT during cold. Specifically, we show that cold markedly down-regulates ANGPTL4 in BAT, likely via activation of AMPK, enhancing LPL activity and uptake of plasma triglyceride-derived fatty acids. In contrast, cold up-regulates ANGPTL4 in WAT, abolishing a cold-induced increase in LPL activity. Together, our data indicate that ANGPTL4 is an important regulator of plasma lipid partitioning during sustained cold.

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Author details

  1. Wieneke Dijk

    Nutrition, Metabolism and Genomics group, Division of Human Nutrition, Wageningen University, Wageningen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.

  2. Markus Heine

    Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany
    Competing interests
    The authors declare that no competing interests exist.

  3. Laurent Vergnes

    Department of Human Genetics, David Geffen School of Medicine, Molecular Biology Institute, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Mariëtte R Boon

    Department of Medicine, Division of Endocrinology, Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden University, Leiden, Netherlands
    Competing interests
    The authors declare that no competing interests exist.

  5. Gert Schaart

    Department of Human Movement Sciences, Maastricht University, Maastricht, Netherlands
    Competing interests
    The authors declare that no competing interests exist.

  6. Matthijs KC Hesselink

    Department of Human Movement Sciences, Maastricht University, Maastricht, Netherlands
    Competing interests
    The authors declare that no competing interests exist.

  7. Karen Reue

    Department of Human Genetics, David Geffen School of Medicine, Molecular Biology Institute, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.

  8. Wouter D van Marken Lichtenbelt

    Department of Human Biology, Maastricht University Medical Centre, European Society for Medical Oncology, Maastricht, Netherlands
    Competing interests
    The authors declare that no competing interests exist.

  9. Gunilla Olivecrona

    Department of Medical Biosciences/Physiological Chemistry, Umeå University, Umeå, Sweden
    Competing interests
    The authors declare that no competing interests exist.

  10. Patrick CN Rensen

    Department of Medicine, Division of Endocrinology, Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, Netherlands
    Competing interests
    The authors declare that no competing interests exist.

  11. Joerg Heeren

    Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany
    Competing interests
    The authors declare that no competing interests exist.

  12. Sander Kersten

    Nutrition, Metabolism and Genomics group, Division of Human Nutrition, Wageningen University, Wageningen, Netherlands
    For correspondence
    sander.kersten@wur.nl
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: This study was performed in accordance with Directive 2010/63/EU from the European Union. All of the animals were handled according to protocols approved by the Animal Ethics Committees of Wageningen University and Hamburg University (2013007.d, 2013100.b and 34/12).

Human subjects: All subjects signed an informed consent for the study protocol, which was approved by the institutional review board of Maastricht University Medical Centre.

Copyright

© 2015, Dijk et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Wieneke Dijk
  2. Markus Heine
  3. Laurent Vergnes
  4. Mariëtte R Boon
  5. Gert Schaart
  6. Matthijs KC Hesselink
  7. Karen Reue
  8. Wouter D van Marken Lichtenbelt
  9. Gunilla Olivecrona
  10. Patrick CN Rensen
  11. Joerg Heeren
  12. Sander Kersten
(2015)
ANGPTL4 mediates shuttling of lipid fuel to brown adipose tissue during sustained cold exposure
eLife 4:e08428.
https://doi.org/10.7554/eLife.08428

Share this article

https://doi.org/10.7554/eLife.08428

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