4. Discussion
obesity, cardiovascular injuries, muscle cell calcification, inflammation
OBESITY, INFLAMMATION, OBESE, PATHOGENESIS
The current study sought to decipher whether a 12-week CT intervention influences exosome cargo in men with obesity and to determine whether changes in exosomes after intervention were related to changes in cardiometabolic health parameters. Although no significant differences between groups were found in the levels of exosomal proteins after the 12-week CT, a medium to large effect size of exercise on most of the exosomal proteins was found. Moreover, associations of changes in exosomes with changes in cardiometabolic health parameters after 12 weeks were revealed.In general, scientific literature has revealed that exercise promotes the levels of exosome markers CD63, CD81 and Flot-1 [Interestingly, our outcomes reveal several associations between 12W-IC and exosome-carried proteins that could highlight the physiological or clinical implication of exercise-released exosomes on cardiometabolic health parameters of obese participants. Maximal oxygen consumption (VOOn the other hand, elevated levels of extracellular HSP70 have been described in obese persons; however, the behavior of this protein in response to exercise is not clear since both a decreased [Human monocyte differentiation antigen CD14 is a pattern recognition receptor that acts as a co-receptor of TLR4, increasing its activity. However, apart from its proinflammatory canonical role, multiple functions in pathogenesis have arisen, which could be due to its wide range of ligands such as HSP70 or leptin [Another set of relevant findings from our study showed negative relationships of 12W-IC in CD63 with 12W-IC in plasma glucose, plasma insulin, GPT and γ-GT, along with a positive association of 12W-IC in CD81 with 12W-IC in weight and fat mass. Although there is a lack of knowledge about the specific role of exosomal tetraspanins in cardiovascular injuries, vascular smooth muscle cell calcification has been proven to be mediated by regulated exosome secretion enriched with the tetraspanins CD9, CD63 and CD81 [In addition, the present study presented several limitations. Since the obesity pathological state may influence the changes of the exosome cargo in response to exercise, upcoming investigations should include a normal-weight control group. On the other hand, only exosomal protein levels were evaluated, so future research performing particle counting in addition to using different isolation and phenotyping methodologies is needed in order to broaden knowledge about exosomal modifications in response to different concurrent exercise protocols in obesity. Moreover, a different approach focused on exerkines released from adipose tissue could have provided additional information on the beneficial effect of exercise and the consequent release of exosome in obese people. Finally, the small sample size of participants with valid data for all the selected variables constitute a statistical limitation in terms of power; however, as revealed by SMD calculated in Taking all these together, these findings provide a clinical perspective from which implementing exercise programs of CT in obese populations is not only effective and useful in terms of classical cardiometabolic health parameters, but also in the activation of exosomal release that could explain these health benefits and even be mediating others still unknown. Therefore, this study provides an added value to the current scientific evidence by means of showing that supervised CT programs have powerful health effects in obese populations and, of particular interest, that these benefits are also at an exosomal level. Nevertheless, more research is needed to better know to which extent this exosomal response can mediate health benefits and to corroborate the results in a larger sample size.In conclusion, the current investigation revealed associations between exercise-driven variations in some exosomal proteins (CD14, CD63, CD81, Flot-1, GAPDH, HSP60, HSP70) with modifications in body composition (weight and fat mass), markers of inflammation (CRP), as well as cardiorespiratory (VO