title: Diet-induced obesity in mice diminishes hematopoietic stem and progenitor cells in the bone marrow.
abstract: Obesity is associated with chronic low-grade inflammation, characterized by leukocytosis and inflammation in the adipose tissue. Continuous activation of the immune system is a stressor for hematopoietic stem and progenitor cells (HSPCs) in the bone marrow (BM). Here we studied how diet-induced obesity (DIO) affects HSPC population dynamics in the BM. Eight groups of age-matched C57Bl/6 mice received a high-fat diet (45% kilocalories from fat) ranging from 1 d up to 18 wk. The obesogenic diet caused decreased proliferation of lineage(-)Sca-1(+)c-Kit(+) (LSK) cells in the BM and a general suppression of progenitor cell populations including common lymphoid progenitors and common myeloid progenitors. Within the LSK population, DIO induced a shift in stem cells that are capable of self-renewal toward maturing multipotent progenitor cells. The higher differentiation potential resulted in increased lymphoid and myeloid ex vivo colony-forming capacity. In a competitive BM transplantation, BM from obese animals showed impaired multilineage reconstitution when transplanted into chow-fed mice. Our data demonstrate that obesity stimulates the differentiation and reduces proliferation of HSPCs in the BM, leading to a decreased HSPC population. This implies that the effects of obesity on HSPCs hampers proper functioning of the immune system.-Van den Berg, S. M., Seijkens, T. T. P., Kusters, P. J. H., Beckers, L., den Toom, M., Smeets, E., Levels, J., de Winther, M. P. J., Lutgens, E. Diet-induced obesity in mice diminishes hematopoietic stem and progenitor cells in the bone marrow.
authors.affiliation: Department of Medical Biochemistry, Subdivision of Experimental Vascular Biology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands;
authors.forename: Susan M
authors.initials: SM
authors.lastname: van den Berg
authors.affiliation: Department of Medical Biochemistry, Subdivision of Experimental Vascular Biology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands;
authors.forename: Tom T P
authors.initials: TT
authors.lastname: Seijkens
authors.affiliation: Department of Medical Biochemistry, Subdivision of Experimental Vascular Biology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands;
authors.forename: Pascal J H
authors.initials: PJ
authors.lastname: Kusters
authors.affiliation: Department of Medical Biochemistry, Subdivision of Experimental Vascular Biology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands;
authors.forename: Linda
authors.initials: L
authors.lastname: Beckers
authors.affiliation: Department of Medical Biochemistry, Subdivision of Experimental Vascular Biology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands;
authors.forename: Myrthe
authors.initials: M
authors.lastname: den Toom
authors.affiliation: Department of Medical Biochemistry, Subdivision of Experimental Vascular Biology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands;
authors.forename: Esther
authors.initials: E
authors.lastname: Smeets
authors.affiliation: Department of Experimental Vascular Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands; and.
authors.forename: Johannes
authors.initials: J
authors.lastname: Levels
authors.affiliation: Department of Medical Biochemistry, Subdivision of Experimental Vascular Biology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands;
authors.forename: Menno P J
authors.initials: MP
authors.lastname: de Winther
authors.affiliation: Department of Medical Biochemistry, Subdivision of Experimental Vascular Biology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands; Institute for Cardiovascular Prevention, Ludwig Maximillians University, Munich, Germany e.lutgens@amc.uva.nl.
authors.forename: Esther
authors.initials: E
authors.lastname: Lutgens
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology*; D049109:Cell Proliferation; D004032:Diet / Q000009:adverse effects*; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology*
keywords: cBMT; flow cytometry; immune system