High-fat diet disturbs lipid raft/TGF-β signaling-mediated maintenance of hematopoietic stem cells in mouse bone marrow.
Fiche publication
Date publication
janvier 2019
Journal
Nature communications
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BASTIE Jean-Noël, Dr DELVA Laurent, Dr HERMETET François, Dr PAIS DE BARROS Jean-Paul, Dr QUERE Ronan
Tous les auteurs :
Hermetet F, Buffière A, Aznague A, Pais de Barros JP, Bastie JN, Delva L, Quéré R
Lien Pubmed
Résumé
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.
Référence
Nat Commun. 2019 Jan 31;10(1):523