The role of exercise-and high fat diet-induced bone marrow extracellular vesicles in stress hematopoiesis

Abstract

Exercise and obesity regulate hematopoiesis, in part through alterations in cellular and soluble components of the bone marrow niche. Extracellular vesicles (EVs) are components of the bone marrow niche that regulate hematopoiesis; however, the role of exercise training or obesity induced EVs in regulating hematopoiesis remains unknown. To address this gap, donor EVs were isolated from control diet-fed, sedentary mice (CON-SED), control diet-fed exercise trained mice (CON-EX), high fat diet-fed, sedentary mice (HFD-SED), and high fat diet-fed, exercise trained mice (HFD-EX) and injected into recipient mice undergoing stress hematopoiesis. Hematopoietic and niche cell populations were quantified, and EV miRNA cargo was evaluated. EV content did not differ between the four groups. Mice receiving HFD-EX EVs had fewer hematopoietic stem cells (HSCs) (p < 0.01), long-term HSC (p < 0.05), multipotent progenitors (p < 0.01), common myeloid progenitors (p<0.01), common lymphoid progenitors (p < 0.01), and granulocyte-macrophage progenitors (p < 0.05), compared to mice receiving HFD-SED EVs. Similarly, mice receiving EX EVs had fewer osteoprogenitor cells compared to SED (p < 0.05) but enhanced mesenchymal stromal cell (MSC) osteogenic differentiation in vitro (p < 0.05) compared to SED EVs. HFD EVs enhanced mesenchymal stromal cell (MSC) adipogenesis in vitro (p < 0.01) compared to CON EVs. HFD-EX EVs had lower microRNA-193 and microRNA-331-5p content, microRNAs implicated in inhibiting osteogenesis and leukemic cell expansion respectively, compared to HFD-SED EVs. The results identify alterations in EV cargo as a novel mechanism by which exercise training alters stress hematopoiesis and the bone marrow niche.

The association between weight-adjusted waist circumference index and lumbar bone mineral density

“…BMSC can differentiate into osteoblasts and adipocytes [43]. Obesity has been shown to facilitate this cell's conversion to an adipocyte, increasing the percentage of adipocytes and decreasing the percentage of osteoblasts in the bone marrow [44,45]. Furthermore, an aberrant buildup of adipocytes in the bone marrow is one of the risk factors for decreased bone turnover and imbalanced osteoblast activity [46].…”

The association between weight-adjusted-waist index and total bone mineral density in adolescents: NHANES 2011–2018

“…Subsequently, research has indicated that obesity augments the population of adipocytes within the bone marrow while concurrently modifying their metabolic function. The bone marrow houses bone mesenchymal stem cells (BMSCs), which possess the capacity to differentiate into both osteoblasts and adipocytes ( 48 , 49 ). The presence of obesity has been demonstrated to promote the differentiation of BMSCs towards adipocytes, culminating in a heightened presence of adipocytes within the bone marrow and a concomitant reduction in the osteoblast population ( 50 ).…”

Potencial das vesículas extracelulares circulantes de camundongos exercitados no tratamento da obesidade.

“…Estudos em modelo animal mostram que o tratamento de ratos diabéticos com EVs da circulação de camundongos exercitados promove uma melhora na cicatrização de feridas promovendo angiogênese (98), além disso EV liberadas com exercício parecem ter um papel na hematopoiese (99). Estudos in vitro mostram que o tratamento com EVs liberadas com a prática de exercício físico parece ter um papel positivo no processo de envelhecimento e na regeneração muscular (100,101).…”