High-fat diet disturbs lipid raft/TGF-ß signaling-mediated maintenance of hematopoietic stem cells in mouse bone marrow.
Nat Commun
; 10(1): 523, 2019 01 31.
Article
en En
| MEDLINE
| ID: mdl-30705272
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-ß receptor within lipid rafts, associated to impaired Smad2/3-dependent TGF-ß signaling, as the main molecular mechanism of action. Finally, injecting HFD-fed mice with recombinant TGF-ß1 avoids the loss of HSC and alteration of the BM's ability to recover, underscoring the fact that a HFD affects TGF-ß signaling on HSC.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Médula Ósea
/
Células Madre Hematopoyéticas
/
Factor de Crecimiento Transformador beta
/
Microdominios de Membrana
/
Dieta Alta en Grasa
Límite:
Animals
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Francia