Editorial: Exercise intervention on metabolic syndrome: focus on pyroptosis

Topic Exercise intervention on metabolic syndrome: focus on pyroptosisMetabolic syndrome (MetS) involves various dysfunctional metabolic processes, spanning from the subcellular compartments to entire organs, and is associated with serious metabolic diseases including diabetes, obesity, and cardiovascular diseases (CVDs).Exercise has been well-documented as a key interventional strategy to alleviate or treat the syndrome, though the underlying mechanisms remain elusive.For example, aerobic exercise can mitigate impaired vasodilation in diabetic mice by enhancement of BKCa channel protein expression through AMPK/Nrf2/HO-1 pathway (1).In addition, exercise can induce the release of signaling molecules (exerkines) from organs and tissues, which influence various chronic inflammation-related diseases.Thus, exercise plays an important role in regulating metabolism and augmenting the anti-inflammatory effects, providing significant advantages for MetS management (2).Recently, a cell death pattern, pyroptosis, has been shown to be inhibited in exercise-induced improvement of metabolic disorders, implying a novel target for the treatment of MetS and related diseases.Pyroptosis is mediated by inflammasomes and a downstream effector, gasdermin D (GSDMD).The NOD-like receptor family pyrin domain-containing 3 (NLRP3) is a key cytosolic inflammasome, composed of the innate immune receptor protein NLRP3, adapter protein ASC, and inflammatory protease caspase-1.The assembled NLRP3 inflammasome can activate the protease caspase-1 to induce GSDMD-dependent pyroptosis and facilitate the release of IL-1b and IL-18, which further contribute to innate immune defense and homeostatic maintenance.However, aberrant activation of the NLRP3 inflammasome is linked with the pathogenesis of inflammatory diseases (3).For example, human and obese mice studies show that obesity and insulin resistance (IR) are associated with increased NLRP3 expression in adipose tissue (4).Accordingly, targeting the secretion of hormones (5) or activating endogenous substances (6) to resist pyroptosis could be a promising research direction for mitigating MetS.IR and its related factors related to pyroptosis can be improved by exercise training.IR is an important pathological index in overweight/obesity and numerous metabolic disorders, prevalent even in many obese children and adolescents.It is associated with Frontiers in Endocrinology frontiersin.