Corrupted adipose tissue endogenous myelopoiesis initiates diet-induced metabolic disease

  1. Elodie Luche
  2. Virginie Robert
  3. Vincent Cuminetti
  4. Céline Pomié
  5. Quentin Sastourné-Array
  6. Aurélie Waget
  7. Emmanuelle Arnaud
  8. Audrey Varin
  9. Elodie Labit
  10. Patrick Laharrague
  11. Remy Burcelin
  12. Louis Casteilla
  13. Beatrice Cousin  Is a corresponding author
  1. Université de Toulouse, CNRS ERL 5311, EFS, INP-ENVT, Inserm U1031, UPS, France
  2. INSERM U1048, France
  3. Université de Toulouse, EFS, INP-ENVT, Inserm U1031, UPS; BP 84225, France
  4. U1048 , France
  5. STROMALab, France

Abstract

Activation and increased numbers of inflammatory macrophages, in adipose tissue (AT) are deleterious in metabolic diseases. Up to now, AT macrophages (ATM) accumulation was considered to be due to blood infiltration or local proliferation, although the presence of resident hematopoietic stem/progenitor cells (Lin-/Sca+/c-Kit+; LSK phenotype) in the AT (AT-LSK) has been reported. By using transplantation of sorted AT-LSK and gain and loss of function studies we show that some of the inflammatory ATM inducing metabolic disease, originate from resident AT-LSK. Transplantation of AT-LSK sorted from high fat diet-fed (HFD) mice is sufficient to induce ATM accumulation, and to transfer metabolic disease in control mice. Conversely, the transplantation of control AT-LSK improves both AT-inflammation and glucose homeostasis in HFD mice. Our results clearly demonstrate that resident AT-LSK are one of the key point of metabolic disease, and could thus constitute a new promising therapeutic target to fight against metabolic disease.

Article and author information

Author details

  1. Elodie Luche

    STROMALab, Université de Toulouse, CNRS ERL 5311, EFS, INP-ENVT, Inserm U1031, UPS, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Virginie Robert

    STROMALab, Université de Toulouse, CNRS ERL 5311, EFS, INP-ENVT, Inserm U1031, UPS, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Vincent Cuminetti

    STROMALab, Université de Toulouse, CNRS ERL 5311, EFS, INP-ENVT, Inserm U1031, UPS, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Céline Pomié

    INSERM U1048, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Quentin Sastourné-Array

    STROMALab, Université de Toulouse, CNRS ERL 5311, EFS, INP-ENVT, Inserm U1031, UPS, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Aurélie Waget

    INSERM U1048, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Emmanuelle Arnaud

    STROMALab, Université de Toulouse, CNRS ERL 5311, EFS, INP-ENVT, Inserm U1031, UPS, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  8. Audrey Varin

    STROMALab, Université de Toulouse, EFS, INP-ENVT, Inserm U1031, UPS; BP 84225, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  9. Elodie Labit

    STROMALab, Université de Toulouse, CNRS ERL 5311, EFS, INP-ENVT, Inserm U1031, UPS, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  10. Patrick Laharrague

    STROMALab, Université de Toulouse, CNRS ERL 5311, EFS, INP-ENVT, Inserm U1031, UPS, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  11. Remy Burcelin

    U1048 , Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  12. Louis Casteilla

    STROMALab, Université de Toulouse, CNRS ERL 5311, EFS, INP-ENVT, Inserm U1031, UPS, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  13. Beatrice Cousin

    Université de Toulouse, CNRS ERL 5311, EFS, INP-ENVT, Inserm U1031, STROMALab, Toulouse, France
    For correspondence
    beatrice.cousin@inserm.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2952-4601

Funding

Aviesan/AstraZeneca

  • Louis Casteilla
  • Beatrice Cousin

Société Francophone du Diabète

  • Beatrice Cousin

ANR (ANR 16-CE14-0006-01)

  • Beatrice Cousin

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Animals were maintained in accordance to guidelines of the European Community Council. All experimental procedures were done in compliance with European regulations for animal experimentation. The authors have received requested approval from their Institutional Ethic Committee, and from Ministry of National Education, Higher Education and Research (# 2691-2015110616015905) for all the experiments performed.

Reviewing Editor

  1. Michael Czech, University of Massachusetts Medical School, United States

Publication history

  1. Received: January 9, 2017
  2. Accepted: June 28, 2017
  3. Accepted Manuscript published: June 28, 2017 (version 1)
  4. Version of Record published: July 13, 2017 (version 2)

Copyright

© 2017, Luche 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. Elodie Luche
  2. Virginie Robert
  3. Vincent Cuminetti
  4. Céline Pomié
  5. Quentin Sastourné-Array
  6. Aurélie Waget
  7. Emmanuelle Arnaud
  8. Audrey Varin
  9. Elodie Labit
  10. Patrick Laharrague
  11. Remy Burcelin
  12. Louis Casteilla
  13. Beatrice Cousin
(2017)
Corrupted adipose tissue endogenous myelopoiesis initiates diet-induced metabolic disease
eLife 6:e23194.
https://doi.org/10.7554/eLife.23194
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