Corrupted adipose tissue endogenous myelopoiesis initiates diet-induced metabolic disease
- Université de Toulouse, CNRS ERL 5311, EFS, INP-ENVT, Inserm U1031, UPS, France
- INSERM U1048, France
- Université de Toulouse, EFS, INP-ENVT, Inserm U1031, UPS; BP 84225, France
- U1048 , France
- 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.
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Author details
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.
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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Corrupted adipose tissue endogenous myelopoiesis initiates diet-induced metabolic disease
eLife 6:e23194.
https://doi.org/10.7554/eLife.23194
