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.

Unhealthy Stem Cells: When Health Conditions Upset Stem Cell Properties

“…These alterations have been described mainly in the adipose tissue reservoir because of changes to the adipose tissue niche. Nevertheless, some studies have examined the negative effect of obesity for the bone marrow niche [90]. Chronic low-grade inflammation associated with obesity is a stressor for HSCs and MSCs resident in the bone marrow due to the continuous response to cytokine inflammation.…”

“…Chronic low-grade inflammation associated with obesity is a stressor for HSCs and MSCs resident in the bone marrow due to the continuous response to cytokine inflammation. In turn, inflammation causes alterations in the microenvironment with implications for cell production [90]. This therefore implies that obesity impedes proper functioning of the immune system through an impairment in the bone marrow niche [91].…”

Dietary Regulation of Adult Stem Cells

“…Whereas a few weeks of a HFD leads to a reduction in HSC numbers [49,50], a longer-term HFD boosts HSCs numbers and function such as increased myeloid cell colony forming units [51]. Notably, this HFD phenotype is partially reversible; after removal from a HFD, HSC numbers in HFD mice return to that of control mice [51].…”

Diabetes‐mediated myelopoiesis and the relationship to cardiovascular risk

“…In contrast to these studies, however, is a recent publication in which HFD feeding of mice leads to a shift of HSPCs from quiescent to differentiating; this loss of self‐renewing characteristics and decrease in proliferation result in impaired multilineage reconstitution . Similar to other studies, the authors find that HFD feeding induces leukocytosis; however, they report that HFD feeding induces long‐term alterations in the hematopoietic system, including losses of stemness and self‐renewal, which may result in a depletion of the most primitive HSPCs.…”