The NLRP3 inflammasome, as an important component of the innate immune system, plays vital roles in various metabolic disorders. It has been reported that the NLRP3 inflammasome can be activated by a broad range of distinct stimuli, such as K⁺ efflux, mitochondrial dysfunction, lysosomal disruption and trans-Golgi disassembly, etc. However, there has been no well-established model for NLRP3 inflammasome activation so far, especially the underlying mechanisms for mitochondria in NLRP3 inflammasome activation remain elusive. Given that K⁺ efflux is a widely accepted nexus for triggering activation of NLRP3 inflammasome in most previous studies, we sought to elucidate the role of mitochondria in K⁺ efflux-induced NLRP3 inflammasome activation. Here, we demonstrated that inflammation activation by LPS evoked the expression of genes that involved in mitochondrial biogenesis and mitophagy, subsequently mitochondrial mass and mitochondrial membrane potential were also elevated, suggesting the contribution of mitochondria in inflammatory responses. Moreover, we inhibited mitochondrial biogenesis by silencing Tfam and genetic ablation of Tfam abolished the NLRP3 inflammasome activation induced by K⁺ efflux via release of mitochondrial DNA (mtDNA), as deprivation of cellular mtDNA by EtBr treatment could reverse inflammasome activation induced by K⁺ efflux. Collectively, we reveal that mtDNA release induced by K⁺ efflux in macrophages activates NLRP3 inflammasome, and propose that mitochondria may serve as a potential therapeutic target for NLRP3 inflammasome-related diseases.

Obesity is an epidemic all around the world. Weight loss interventions that are effective differ from each other with regard to various lipidomic responses. Here, we aimed to find lipidomic biomarkers that are related to beneficial changes in weight loss. We adopted an untargeted liquid chromatography with tandem mass spectrometry (LC-MS/MS) method to measure 953 lipid species for Exercise (exercise intervention cohort, N = 25), 1388 lipid species for LSG (laparoscopic sleeve gastrectomy cohort, N = 36), and 886 lipid species for Cushing (surgical removal of the ACTH-secreting pituitary adenomas cohort, N = 25). Overall, the total diacylglycerol (DG), triacylglycerol (TG), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylserine (PS), and sphingomyelin (SM) levels were associated with changes in BMI, glycated hemoglobin (HbA1c), triglyceride, and total cholesterol according to weight loss interventions. We found that 73 lipid species changed among the three weight loss interventions. We screened 13 lipid species with better predictive accuracy in diagnosing weight loss situations in either Exercise, LSG, or Cushing cohorts (AUROC > 0.7). More importantly, we identified three phosphatidylcholine (PC) lipid species, PC (14:0_18:3), PC (31:1), and PC (32:2) that were significantly associated with weight change in three studies. Our results highlight potential lipidomic biomarkers that, in the future, could be used in personalized approaches involving weight loss interventions.

Objective: Type 2 diabetes (T2D) is a common chronic metabolic disease, and its prevalence is increasing globally. Exercise is crucial for T2D management, yet many aspects of its mechanisms remain unclear. This study employs CiteSpace to reveal research hotspots and frontier issues in exercise intervention for T2D.Method: A literature review spanning from January 1, 2013 to December 31, 2022, was conducted using the Web of Science Core Collection (WoSCC), with keywords including “exercise,” “type 2 diabetes,” and “mechanisms.” We analyzed network diagrams generated by CiteSpace, which depicted relationships among countries, authors, and keywords.Results: This study includes 1,210 English papers from 555 journals, affiliated with 348 institutions across 80 countries/regions. Notably, the United States, China, and the United Kingdom account for nearly half of all publications. The University of Copenhagen leads in publication volume, followed by Harvard Medical School and the University of Colorado. Key authors include Kirwan, John P (Case Western Reserve University), Malin, Steven K (Rutgers University), and Pedersen, Bente Klarlund (University of Copenhagen). Based on co-occurrence analysis of keywords, it is evident that terms such as “disease,” “glucagon-like peptide 1,” and “cardiovascular risk factor” exhibit high intermediary centrality.Conclusion: The analysis highlights ongoing investigations into molecular mechanisms, such as β-cell function enhancement, exerkines, and epigenetic mechanisms. Emerging areas include exercise response heterogeneity, circadian rhythm regulation, transcription factors, neurotrophic factors, and mitochondrial function. Future studies should prioritize understanding interactions between different exercise mechanisms and optimizing exercise prescriptions for T2D. Exercise prescriptions are crucial for effective interventions. Collaboration between countries and institutions is essential to understand the influences of different genetic backgrounds and environmental factors. Currently, a combination of aerobic and resistance training is considered the optimal form of exercise. However, considering time efficiency, high-intensity interval training (HIIT) has gained widespread attention and research due to its ability to achieve similar exercise effects in a shorter duration. Additionally, circadian rhythm regulation may affect the exercise outcomes of diabetic individuals at different times of the day, particularly concerning the specific types, doses, and intensities used for precision intervention in T2D.

High-intensity interval training (HIIT) has been shown in studies to enhance glucose management and cardiovascular well-being in patients with type 2 diabetes. In this study, we used power cycling to assess the physical activity levels of men with type 2 diabetes during a single low-volume HIIT session. First, fifty-six men with type 2 diabetes volunteered to take part in the study, and they were split into two groups based on the International Physical Activity Scale Short Form (IPA). To the first 1–4 labor bouts, both the sufficiently physically active and insufficiently physically active groups exhibited equal positive emotional reactions ( ). However, over time (about 5–10 times), both of them showed reduced emotional reactions, with a significant difference ( ). The insufficiently physically active group had lower mean emotional response, lowest effective response, and maximum effective response values than the sufficiently physically active group ( ), while the difference in RPE between the two groups was not statistically significant ( ). From the standpoint of emotional response, the proposed model shows that HIIT or reduced volume HIIT exercise prescriptions should be utilized with caution in physical activity programs for novices and less active and chronically sick persons. The frequency, intensity, and effects of low-volume HIIT on individuals’ emotional reactions and health conditions in the T2DM group are also investigated. Furthermore, this low-volume HIIT program can be successfully applied in the real-world setting of people who are not physically active enough or who are chronically unwell.

Purpose: To examine how baseline insulin resistance (IR) modulates exercise-induced changes in systemic immune-inflammation index (SII) and metabolic parameters in type 2 diabetes mellitus (T2DM). Methods: Fifty-five T2DM patients stratified by fasting C-peptide tertiles into low- (Group 1), moderate- (Group 2), and high-IR groups (Group 3) completed a 4-week moderate-intensity combined aerobic-resistance exercise program. Changes in SII (neutrophils × platelets/lymphocytes), anthropometrics, and glucolipid markers were assessed, with ANCOVA and hierarchical regression modeling intergroup differences and predictors (Clinical Trial Registration ID: ChiCTR2200066710). Results: Significant reductions in weight, BMI, and body fat% occurred in Group 1/Group 2 (all p <0.05) but not Group 3. SII decreased in Group 1 ( p <0.05) yet increased in Group 3 due to neutrophil elevation ( p <0.05). Fasting glucose and HbA1c improved across all groups ( p <0.05), with Group 3’s glycemic benefits independent of weight loss or anti-inflammatory effects. Baseline C-peptide independently predicted increases in ΔSII across all adjusted models (β=19.85–21.94, p <0.01), whereas covariates including age, diabetes duration, and BMI showed no significant effects. Conclusion: Severe baseline IR attenuates exercise-mediated SII improvement and body composition optimization, whereas glycemic benefits remain IR-independent, necessitating IR-stratified exercise prescriptions. Clinical trial registration: Chinese Clinical Trial Registry, identifier ChiCTR2200066710.