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 lineagēSca-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.
Original language | English (US) |
---|---|
Pages (from-to) | 1779-1788 |
Number of pages | 10 |
Journal | FASEB Journal |
Volume | 30 |
Issue number | 5 |
DOIs | |
State | Published - May 2016 |
Keywords
- CBMT
- Flow cytometry
- Immune system
ASJC Scopus subject areas
- Biotechnology
- Biochemistry
- Molecular Biology
- Genetics