1. Microbiota from Obese Mice Regulate Hematopoietic Stem Cell Differentiation by Altering the Bone Niche.
- Author
-
Luo Y, Chen GL, Hannemann N, Ipseiz N, Krönke G, Bäuerle T, Munos L, Wirtz S, Schett G, and Bozec A
- Subjects
- Adipocytes metabolism, Animals, Bone Marrow Cells metabolism, Diet, High-Fat, Gastrointestinal Microbiome, Mice, Mice, Obese metabolism, Mice, Obese microbiology, Microbiota, Myeloid Cells cytology, Osteoblasts metabolism, Cell Differentiation, Hematopoietic Stem Cells metabolism, Myeloid Cells metabolism, Stem Cell Niche, Stress, Physiological
- Abstract
The effect of metabolic stress on the bone marrow microenvironment is poorly defined. We show that high-fat diet (HFD) decreased long-term Lin(-)Sca-1(+)c-Kit(+) (LSK) stem cells and shifted lymphoid to myeloid cell differentiation. Bone marrow niche function was impaired after HFD as shown by poor reconstitution of hematopoietic stem cells. HFD led to robust activation of PPARγ2, which impaired osteoblastogenesis while enhancing bone marrow adipogenesis. At the same time, expression of genes such as Jag-1, SDF-1, and IL-7 forming the bone marrow niche was highly suppressed after HFD. Moreover, structural changes of microbiota were associated to HFD-induced bone marrow changes. Antibiotic treatment partially rescued HFD-mediated effects on the bone marrow niche, while transplantation of stools from HFD mice could transfer the effect to normal mice. These findings show that metabolic stress affects the bone marrow niche by alterations of gut microbiota and osteoblast-adipocyte homeostasis., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF