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Nat Commun. 2019 Jan 31;10(1):523. doi: 10.1038/s41467-018-08228-0.

High-fat diet disturbs lipid raft/TGF-β signaling-mediated maintenance of hematopoietic stem cells in mouse bone marrow.

Author information

1
Signaling and Physiology in Hematological Research, INSERM, UMR1231, Université Bourgogne Franche-Comté, Dijon, 21000, France.
2
LipSTIC LabEx, Fondation de Coopération Scientifique Bourgogne Franche-Comté, Dijon, 21000, France.
3
Plateforme de Lipidomique, Université Bourgogne Franche-Comté, Dijon, 21000, France.
4
Hôpital Universitaire François Mitterrand, Service d'Hématologie Clinique, Dijon, 21000, France.
5
Signaling and Physiology in Hematological Research, INSERM, UMR1231, Université Bourgogne Franche-Comté, Dijon, 21000, France. ronan.quere@inserm.fr.
6
LipSTIC LabEx, Fondation de Coopération Scientifique Bourgogne Franche-Comté, Dijon, 21000, France. ronan.quere@inserm.fr.

Abstract

Despite recent in vivo data demonstrating that high-fat diet (HFD)-induced obesity leads to major perturbations in murine hematopoietic stem cells (HSC), the direct role of a HFD is not yet completely understood. Here, we investigate the direct impact of a short-term HFD on HSC and hematopoiesis in C57BL/6J mice compared with standard diet-fed mice. We detect a loss of half of the most primitive HSC in the bone marrow (BM) cells of HFD-fed mice, which exhibit lower hematopoietic reconstitution potential after transplantation. Impaired maintenance of HSC is due to reduced dormancy after HFD feeding. We discover that a HFD disrupts the TGF-β receptor within lipid rafts, associated to impaired Smad2/3-dependent TGF-β signaling, as the main molecular mechanism of action. Finally, injecting HFD-fed mice with recombinant TGF-β1 avoids the loss of HSC and alteration of the BM's ability to recover, underscoring the fact that a HFD affects TGF-β signaling on HSC.

PMID:
30705272
PMCID:
PMC6355776
DOI:
10.1038/s41467-018-08228-0
[Indexed for MEDLINE]
Free PMC Article

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