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

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-beta receptor within lipid rafts, associated to impaired Smad2/3-dependentTGF-beta signaling, as the main molecular mechanism of action. Finally, injecting HFD-fed mice with recombinant TGF-beta 1 avoids the loss of HSC and alteration of the BM's ability to recover, underscoring the fact that a HFD affects TGF-beta signaling on HSC.