Lifestyle and exercise effects on circulating progenitor cells in children and adults

Obesity is a growing concern in today’s world with about two thirds of adults and one third of children classified as overweight or obese. Childhood obesity is a growing public health concern because children who are living with obesity are more likely to live with obesity in adulthood. Obesity is associated with chronic low-grade inflammation characterized by elevating inflammatory proteins and a chronically activated immune system, which is maintained by circulating progenitor cells (CPCs). CPCs are a heterogeneous population of cells that are capable of replenishing the immune system after a hematopoietic stem cell transplant. CPCs reside within the bone marrow niche whereby upon appropriate stimuli, will be enticed into the peripheral blood. Additionally, CPCs can differentiate into mature immune cells of both the myeloid and lymphoid immune lineage. Cell surface receptors on CPCs, such as TLR4, may influence a myeloid bias of differentiation of CPCs. CPCs expressing CCR2 may also be primed to mobilize to inflamed peripheral tissue. Of interest, monocytes are a mature myeloid cell population and peruse the peripheral blood to which they will infiltrate inflamed peripheral tissue in order to differentiate into macrophages. Monocytes can also express both TLR4 and CCR2, and these receptors may play a role in myeloid immune system activation seen in persons with obesity. Both CPCs and monocytes have been shown to be increased in circulation in both adults and children living with obesity, suggesting that inflammation may play a role in CPC mobilization. On the other hand, a vast amount of research has shown that acute endurance exercise, possibly linked to exercise-induced inflammation, transiently increases CPC concentration in the peripheral blood. However, less is clear about the effects of exercise training on CPC concentrations, given that exercise training is anti-inflammatory. To date, no research has examined the anti-inflammatory effects of endurance exercise training on CPCs in persons with obesity. Lastly, previous research has indicated a potential pro-inflammatory effect of macronutrient composition of meals in healthy adults. Given the close relationship of chronic inflammation in persons with obesity, it is possible that there may be a relationship between macronutrient composition of meals and children living with overweight or obesity. Thus, the purpose of this thesis was to investigate the role of exercise and nutrition on CPCs and inflammatory monocytes in obesity. This dissertation is divided into four sections. First, we review the literature available pertaining to CPCs, CPC mobilization and potential fates of mobilized CPCs, inflammatory monocytes, inflammatory cytokines, and nutrition in obesity. Subsequently, for our first experiments we examined inflammatory monocytes and the relationship between HSPCs (a subset of CPCs) in children with overweight and obesity and cognition. We collected blood from children and measured HSPC and inflammatory monocyte content. Next, we correlated measures of cognition with HSPC concentrations and observed that overweight and obese children had a positive relationship with HSPC content and cognition; and that healthy weight children had a negative relationship with HSPC content and cognition, with a significant difference between the two relationships. Moreover, we found that conditioned media from cultured CPCs from children with overweight and obesity caused increased neurogenesis in vitro but not from healthy weight children. Following this, we next aimed to examine the effects of endurance exercise training on CPCs and their subpopulations, as well as those expressing inflammatory markers, in lean individuals and individuals with obesity. We found that endurance exercise training decreases CPCs, HSPCs, and HSPCs expressing inflammatory receptors irrespective of weight status, further supporting the anti-inflammatory effects of exercise. In the final experiment, we examined the relationship between inflammatory monocytes expressing inflammatory receptors and the acute effects of feeding of meals of different macronutrients in children of differing weight status. We found that after a carbohydrate rich meal, children who were overweight or obese had a reduced percentage of intermediate monocytes expressing inflammatory markers, suggesting their infiltration to peripheral tissue. In summary, we show that CPCs are increased in children with overweight and obesity; and that endurance exercise training decreases HSPCs expressing inflammatory receptors in adults with obesity. Additionally, inflammatory monocytes are increased in children with overweight and obesity. Moreover, we show, for the first time, that a carbohydrate rich meal causes a decrease in inflammatory monocytes in the peripheral blood. In turn, these data will assist in the characterization of CPCs and inflammatory monocytes to certain anti-inflammatory or pro-inflammatory stimuli. Further characterizing CPCs and their subpopulations, and inflammatory monocytes, in the context of obesity, will help in the formulation of interventions to optimize health during obesity in childhood and adulthood.LimitedAuthor requested closed access (OA after 2yrs) in Vireo ETD syste