Role of the physical exercise in the NLRP3 inflammasome and Obesity biomarkers

Abstract

Obesity is a chronic disease that affects millions of people worldwide. Currently, the prevalence of overweight and Obesity affects approximately 39% of the world population today. It is known that Obesity is closely associated with inflammation, which leads to increased production of cytokines mediated by the activation of a complex of intracellular proteins called inflammasomes, among which the most studied in the metabolic context has been NLRP3. Monocytes play a central role in the chronic inflammatory process, and studies show that Obesity promotes modulation in the phenotype of the three subtypes of monocytes, classified as classical (CD14++CD16-), intermediate (CD14++CD16+) and non-classical (CD14+CD16++). Recruitment of the different monocyte subtypes is determined by the expression of the monocyte chemokine receptors CCR2, CCR5 and CX3CR1. Although it is accepted that physical exercise brings benefits associated with Obesity, little is known about the modulation of the NLRP3 inflammasome, monocyte subtypes and chemokine receptors induced by High-Intensity Interval Training (HIIT) in obese individuals. Thus, the aim of the present study is to evaluate a possible modulation of the NLRP3 inflammasome (and related interleukins), monocyte subtypes and chemokine receptors in obese subjects after high-intensity interval training compared to untrained subjects. Obese, sedentary individuals (approximately 84) from both sexes, aged between 18 and 60 years, will be invited to voluntarily participate in the present study and then separated into two groups: trained (three weekly HIIT sessions, for a period of eight weeks) and untrained group (control). Body composition assessment will be performed by DEXA; the systemic levels of adipokines (leptin, resistin, and adiponectin), as well as the cytokines IL-1beta, IL-6, IL-10, and TNF-alfa, both in serum as in culture of mononuclear cells and monocyte isolated by beads, stimulated or not with LPS and nigericin, will be evaluated by ELISA; the monocyte subtypes and the NLRP3 inflammasome will be evaluated by flow cytometry; NLRP3 will be also evaluate by real time PCR as well as the chemokine receptors CCR2, CCR5 and CX3CR1, before and after the training period. It will also be performed the interaction analysis of gene pathways of the parameters to be evaluated (NLRP3 inflamassome and associated interleukins, pro and anti-inflammatory cytokines, CCR2, CCR5 and CX3CR1 receptors). (AU)