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

François Hermetet, Anne Buffière, Aziza Aznague, Jean-Paul Pais de Barros, Jean-Noël Bastie, Laurent Delva and Ronan Quéré ()
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François Hermetet: INSERM, UMR1231, Université Bourgogne Franche-Comté
Anne Buffière: INSERM, UMR1231, Université Bourgogne Franche-Comté
Aziza Aznague: INSERM, UMR1231, Université Bourgogne Franche-Comté
Jean-Paul Pais de Barros: LipSTIC LabEx, Fondation de Coopération Scientifique Bourgogne Franche-Comté
Jean-Noël Bastie: INSERM, UMR1231, Université Bourgogne Franche-Comté
Laurent Delva: INSERM, UMR1231, Université Bourgogne Franche-Comté
Ronan Quéré: INSERM, UMR1231, Université Bourgogne Franche-Comté

Nature Communications, 2019, vol. 10, issue 1, 1-11

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-018-08228-0

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