title: Diet-induced obesity promotes myelopoiesis in hematopoietic stem cells.
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.
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Kanakadurga
authors.initials: K
authors.lastname: Singer
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: DelProposto
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: David Lee
authors.initials: DL
authors.lastname: Morris
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Zamarron
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Taleen
authors.initials: T
authors.lastname: Mergian
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Nidhi
authors.initials: N
authors.lastname: Maley
authors.affiliation: Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University, 25 Bongjeong-ro Dongnam-gu, Cheonan-si, Chungcheongnam-do 330-930, South Korea.
authors.forename: Kae Won
authors.initials: KW
authors.lastname: Cho
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Lynn
authors.initials: L
authors.lastname: Geletka
authors.affiliation: Department of Mathematics and Statistics, Oakland University, Rochester, MI, USA.
authors.forename: Perla
authors.initials: P
authors.lastname: Subbaiah
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Lindsey
authors.initials: L
authors.lastname: Muir
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Martinez-Santibanez
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Carey Nien-Kai
authors.initials: CN
authors.lastname: Lumeng
keywords: Hematopoietic stem cells; Myelopoiesis; Obesity