Fat or thin, exercise wins: endurance exercise training reduces inflammatory circulating progenitor cells in lean and obese adults

Exercise is a well-documented, nonpharmaceutical intervention with the potential to impact upon the various comorbidities associated with obesity. While often considered for its contribution to cardiovascular health, endurance exercise in particular may play an important role in the reduction of the low-grade systemic inflammation that is associated with obesity and metabolic dysfunction. The increase in cytokine production associated with activated inflammatory pathways may portend disruption in lipid metabolism, thereby actively contributing to the development of atherosclerosis and other major health issues associated with a chronic inflammatory state (Ridker et al. 2000). Thus, a greater understanding of the role of early inflammatory mediators may aid in predicting inflammatory potential and capacity for deterioration. Circulating progenitor cells (CPCs) are a relatively nondescript cell group comprising endothelial progenitor cells (EPCs), mesenchymal stem cells (MSCs) and haematopoietic stem cells (HSCs), which further differentiate into haematopoietic stem/progenitor cells (HSPCs). HSPC populations, when stimulated, potentiate myeloid lineages that eventually form key inflammatory cells. In addition, CPC levels have previously been shown to be elevated in the peripheral tissues of obese individuals, thus suggesting that these cell types may represent a surrogate marker for inflammatory potential (Bellows et al. 2011). In order to determine the true effect of an endurance exercise training (EET) regimen on CPC population differentiation, Niemiro et al. (2018) studied both lean and obese individuals enrolled in a closely monitored EET protocol, in an article in a recent issue of The Journal of Physiology. This is the first study to consider the effect of a strict 6-week steady-state EET programme on CPC differentiation specifically within an obese adult population. The group conducted the study with the hypothesis that EET would decrease the quantity of HSPCs expressing inflammatory markers as well as the relative quantity of differentiated inflammatory cells in obese individuals when compared to lean individuals on the same programme. Niemiro and colleagues appear to draw from the cohort of sedentary lean (n = 17; BMI 22 ± 2.6 kg m−2) and obese individuals (n = 10; BMI 33.1 ± 6.0 kg m−2) that were previously investigated for exercise-related shifts in intestinal microbiome composition and functionality by Allen and colleagues (2018). Although the group sample sizes are notably low, it is notoriously difficult to recruit and retain participants within exercise studies due to the considerable temporal and physical commitment required of them. In line with this, the authors demonstrate excellent trial management in attaining complete compliance from all participants, thereby bolstering the power of the dataset and conclusions drawn. Participants underwent baseline testing that entailed a dual X-ray absorptiometry scan, assessment of blood progenitor cell concentrations and proportions, maximal exercise test and analysis of dietary intake. V̇O2max was determined during maximal exercise testing, which was performed under the widely recognized Bruce protocol. Despite the use of a standardized exercise tolerance test, the authors offered participants two modalities of exertion – cycle ergometer or treadmill – thereby introducing a largely controllable variable that has been previously demonstrated to impact upon the results of such assessments, as treadmill exercise draws from a larger group of muscles and thus allows for a greater improvement of oxygen utilization (Muscat et al. 2015). Therefore, it would be of interest to know the distribution of modality used in both groups and whether participants were instructed to select the same exercise method for the subsequent V̇O2max testing. Following the baseline assessments, both lean and obese participants were enlisted in a 6-week EET scheme involving three supervised 30–60 min sessions per week of incrementally increasing intensity. Upon completion of the exercise training programme, participants underwent the same battery of assessments, to allow for comparison of both the exercise and BMI × exercise effects. During baseline testing, obese participants were found to have higher percentage body fat and a significantly lower V̇O2max. At 40.3 ml kg−1 min−1, the lean subjects displayed ‘fair’ to ‘good’ performance during baseline V̇O2max testing, while the obese group demonstrated ‘very poor’ to ‘fair’ baseline V̇O2max at 31.5 ml kg −1 min−1. It is important to note, however, that sex was not ideally balanced between the lean and obese groups, at 47% and 70% female, respectively. This may have affected the average V̇O2max performance substantially, as females have inherently lower V̇O2max, thus potentially skewing the interpretation of the results. Finally, although the average number of granulocytes and granulocyte– macrophages was found to be higher in the obese individuals at baseline, no significant difference was observed in any blood progenitor cell concentrations or proportions between the groups. Interestingly, circulating progenitor cell concentrations have previously been shown to display sex specificity (Topel et al. 2017); this is again of relevance to the current study, due to the sex imbalances observed between the groups. In analysing diluent plate counts of peripheral blood mononuclear cells postintervention, the authors demonstrated a significant attenuating effect of EET on both granulocytes and granulocyte–macrophage populations, independently of BMI class. Despite this, obese individuals displayed significantly higher levels of both innate immune cell types before and after EET. Interestingly, a substantial reduction was noted in both CPCs and a uniquely inflammatory-primed subset thereof, termed HSPCs. This subset undergoes differentiation towards more lymphoid or myeloid lineages depending on haematological triggers that, in turn, affect the systemic inflammatory tone. In line with these results, the authors noted a significant reduction in CPC-mobilizing