Subjects with obesity go through a process known as low-grade chronic inflammation, in turn, this represents a risk factor for the development of metabolic disorders and several diseases, such as non-alcoholic steatohepatitis (NASH) and even cancer. There are different nutritional strategies for the obesity approach, among which, lifestyle changes are the most successful [12]. However, it is important to note that regular exercise has an important anti-inflammatory response. Therefore, we evaluated the effect of a four-month exercise program on ASC mRNA expression and inflammatory markers in obese adults, and we demonstrated that ASC mRNA expression was decreased in obese participants after the diet-exercise program, and a significant difference was found compared to the diet-group at the end of the intervention. These results show that exercise has an effect on the expression of the ASC gene.
Other studies have demonstrated hypermethylation of the ASC gene in heart failure patients and in older individuals after exercise, and in turn, methylation was positively correlated with the expression of ASC and IL-1 family, therefore, exercise may play an important role in the epigenetic modification of the ASC gene [7,8,13,14]. Although in this study we did not measure IL-1β or IL-18 expression, we quantified both cytokines; however, no significant differences were found probably because our study population did not have another metabolic disease.
Thus, we propose the ASC gene as a biomarker in response to the exercise intervention to attenuate inflammation in obese individuals and prevent the consequences of low-grade inflammation, since we also observed a negative correlation between the delta of ASC mRNA expression and IL-10 levels in the diet-exercise group.
Interleukin-10 (IL-10) is an important anti-inflammatory cytokine that is associated with the immune response [15], the inhibition of IL-1α, IL-1β, IL-6, IL-8, TNF-α proinflammatory cytokines [16] and the suppression of the NFk-B signaling pathway [17]. Therefore, our results are of interest since the down-regulation of the ASC gene in response to the exercise program could be related to the NFk-B signaling pathway, however, this should be explored in future studies.
Furthermore, we also found MCP-1 and MIP-1β decreased levels after the exercise program, and these cytokines are synthesized by monocytes and macrophages [18,19], the main cells where NLRP3 inflammasome is activated [9]. Both cytokines are related to cardiovascular alterations and atherogenic development and are stimulated by proinflammatory cytokines, such as IL-1β. Therefore, we could expect from our findings that the exercise program had a role in the decrease of NLRP3 inflammasome activation through ASC down-regulation, MCP-1, and MIP-1β; thus, improving the anti-inflammatory profile through the IL-10 cytokine.
Moreover, visceral adipose tissue surrounding the internal organs has inflammatory activity since it is associated with a greater number of pro-inflammatory cells in the tissue [20]. Therefore, the decreased levels of MCP-1, MIP-1β and IL-8 cytokines in our study also may be in part due to the abdominal fat loss, since these results showed a positive correlation between them (p<0.05).
In this study, both intervention groups improved body composition, which was consistent with other studies where the effect of hypocaloric diets accompanied or not by three months of an exercise intervention program, decreased the same variable [21,22]. These results are expected and partly explained due to the energy restriction involving the activation of lipolytic metabolic pathways, which increase the use of adipose tissue as stored energy [23]. Besides, if the demand for energy increases, as in exercise, the mobilization of fatty acids from stored adipose tissue also increases [24].
In addition, we observed that the participants who performed the diet-exercise program did not have significant changes in musculoskeletal and fat-free mass compared to the diet-group, so this indicates that the weight loss was mainly in fat mass. This finding demonstrates some of the additional benefits of exercise in weight loss management since adding exercise training to energy restriction results in favorable body composition changes in obese subjects. Our results are in accordance with other authors who reported that diet-exercise interventions for six months preserved lean body mass or skeletal muscle mass compared to only diet interventions in obese adults [25,26].
Abdominal obesity has been associated with systemic inflammation [27] and metabolic risk [28]. However, in our study, we found that 26.7% of the participants who performed exercise decreased abdominal obesity, and this was significant when compared to the diet-group. Our result is consistent with other studies, which show that regular exercise reduces visceral fat, independent of weight reduction [29, 30]. Moreover, O'Donovan et al. found that overweight subjects with better physical fitness had lower visceral fat than the overweight unfit group [31]. Our results and the evidence mentioned above highlighted the effect of exercise on abdominal fat loss, suggesting that systemic inflammation decreased regardless of weight loss.
In our study, the diet-exercise group showed a tendency to decrease the atherogenic index at the end of the intervention, and a statistical difference was found when we compared the atherogenic index change between groups. Our finding is similar to other results that show an association of exercise with the atherogenic index of plasma after twelve weeks of aerobic exercise in obese individuals [32], as well as a lower atherogenic index in subjects who performed regular exercise compared to sedentary subjects [33]. Lastly, an inverse association was found between the atherogenic index and physical activity levels [34].
In addition, there is evidence that associates obesity as a precursor of atherosclerosis, particularly central adiposity, which is usually determined by waist circumference [35]. In this sense, we found a positive correlation between the atherogenic index and waist circumference in the diet-exercise group, and it is important to mention that this group had a greater abdominal fat loss. Therefore, our results support the evidence that the loss of abdominal obesity could decrease the risk of atherosclerosis, and subsequently, the risk of cardiovascular diseases. This finding highlights the benefits of exercise as a cardio-protector factor.
Given our findings, we believe it is important to consider the measurement of ASC methylation, and the expression of the IL-1 family in obese subjects. Also, there were limitations in our study as small sample size and the high dropout rate in the exercise group, which could be due to the lack of commitment and poor adherence to achieve a healthy habit over a long period of time, as well as the subjective method used to quantify the VO2max, and accelerometers were not used in each exercise sessions. Future researches are needed to done in the same population to support our results and the mechanism of ASC downregulation through exercise and including more markers related to low-grade chronic inflammation pathway.