Diet-induced obesity in mice diminishes hematopoietic stem and progenitor cells in the bone marrow

Berg, Susan M. van den; Seijkens, Tom T. P.; Kusters, Pascal J. H.; Beckers, Linda; Toom, Myrthe; den Smeets, Esther; Levels, Johannes; Winther, Menno P. J. de und Lutgens, Esther (2016): Diet-induced obesity in mice diminishes hematopoietic stem and progenitor cells in the bone marrow. In: FASEB Journal, Bd. 30, Nr. 5: S. 1779-1788

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 C57B1/6 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. Ina 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., denToom, 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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0892-6638
• Sprache: Englisch