Inflamação, Exercício Físico e Armadilhas de Neutrófilos Extracelulares (NETs) no tecido adiposo e Avaliação dos efeitos crônicos do Exercício Físico intenso no tecido adiposo de camundongos obesos

Abstract

Obesity results from the excessive accumulation of body fat and chronic low-grade inflammation. Physical exercise, at different intensities, modulates metabolic and inflammatory pathways, establishing itself as a therapeutic strategy. From this perspective, the present study aimed to evaluate inflammation, physical exercise, and neutrophil extracellular traps (NETs) in adipose tissue, as well as the chronic effects of intense physical exercise on the adipose tissue of obese mice. The first product of this thesis consisted of a review with bioinformatics analysis, which explored the relationship between physical exercise, obesity, and NETs. The review showed that NET formation, although essential for combating pathogens, can contribute to the worsening of chronic inflammation and metabolic dysfunction in obesity. The in silico analysis identified genes and signaling pathways associated with NETs that are modulated by exercise, including TNF-α, IL-6, and TLR4, all of which are related to inflammatory activation, oxidative stress, and metabolic regulation. These findings indicate that regular physical exercise may reduce the exacerbated activation of these structures, thereby attenuating systemic inflammatory processes. The study also highlighted the difference between the acute and chronic effects of physical exercise, where acute stimuli tend to increase the release of pro-inflammatory cytokines and NET formation, whereas chronic exercise exerts a regulatory effect, reducing low grade inflammation associated with obesity. This product reinforces the importance of physical exercise as a non-pharmacological strategy to modulate immune and inflammatory responses. The second product experimentally evaluated the impact of high-intensity continuous aerobic exercise on the adipose tissue of mice with diet induced obesity. To this end, the study investigated the signaling pathways mTORC, AKT, GATOR2, SESN2, and GPX1, which are related to energy metabolism, oxidative stress, and adaptive responses to exercise. Three groups of SWISS mice were used in the experiment: the control group (standard diet), the HFD group (obese without exercise), and the HFD + HICT group (obese fed a high-fat diet and subjected to a high-intensity continuous aerobic training protocol for eight weeks). During the treatment period, body weight was measured. At the end of the experiment, glucose tolerance and insulin sensitivity tests were performed to assess glycemic metabolism. The animals were then sacrificed by decapitation, and blood samples were collected for biochemical analyses. The study was approved by the Experimental Research Ethics Committee of the State University of Montes Claros. The main findings showed that trained mice had a significant reduction in body weight, total cholesterol, and HDL. In addition, high-intensity training decreased adipocyte size in epididymal adipose tissue and reduced adiposity. Significant modulation was also observed in the expression of genes essential for the regulation of metabolism and the response to oxidative stress, such as MTOR, AKT, GATOR2, SESN2, and GPX1. This study contributed to the understanding of the metabolic effects of HICT in obesity, demonstrating a possible mechanism of action via mTOR signaling, with impacts on energy metabolism and oxidative stress response. In conclusion, this thesis demonstrated that physical exercise can modulate NETs and inflammation, in addition to promoting adipose tissue remodeling and activating metabolic pathways, thus representing a promising strategy for the management of obesity