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Diet-induced obesity promotes myelopoiesis in hematopoietic stem cells

Authors
Singer, KanakadurgaDelProposto, JenniferMorris, David LeeZamarron, BrianMergian, TaleenMaley, NidhiCho, Kae WonGeletka, LynnSubbaiah, PerlaMuir, LindseyMartinez-Santibanez, GabrielLumeng, Carey Nien-Kai
Issue Date
Sep-2014
Publisher
Elsevier GmbH
Keywords
Obesity; Hematopoietic stem cells; Myelopoiesis
Citation
Molecular Metabolism, v.3, no.6, pp 664 - 675
Pages
12
Journal Title
Molecular Metabolism
Volume
3
Number
6
Start Page
664
End Page
675
URI
https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/11919
DOI
10.1016/j.molmet.2014.06.005
ISSN
2212-8778
Abstract
Obesity is associated with an activated macrophage phenotype in multiple tissues that contributes to tissue inflammation and metabolic disease. To evaluate the mechanisms by which obesity potentiates myeloid activation, we evaluated the hypothesis that obesity activates myeloid cell production from bone marrow progenitors to potentiate inflammatory responses in metabolic tissues. High fat diet-induced obesity generated both quantitative increases in myeloid progenitors as well as a potentiation of inflammation in macrophages derived from these progenitors. In vivo, hematopoietic stem cells from obese mice demonstrated the sustained capacity to preferentially generate inflammatory CD11c(+) adipose tissue macrophages after serial bone marrow transplantation. We identified that hematopoietic MyD88 was important for the accumulation of CD11c(+) adipose tissue macrophage accumulation by regulating the generation of myeloid progenitors from HSCs. These findings demonstrate that obesity and metabolic signals potentiate leukocyte production and that dietary priming of hematopoietic progenitors contributes to adipose tissue inflammation. (C) 2014 The Authors. Published by Elsevier GmbH.
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