To investigate the effects of aerobic exercise, caloric restriction, and their combined intervention on NLRP3 inflammasome activation and macrophage M1/M2 polarization in the liver of db/db mice, and to elucidate their potential mechanisms in alleviating hepatic inflammation. Thirty-two mice were randomly divided into four groups (n=8/group): control (CON), aerobic exercise (AE), caloric restriction (CR), and combined intervention (ECR). The AE group underwent treadmill running at 50%-55% VO2max for 1 h/day, 5 days/week. The CR group received 70% of the CON group’s daily food intake. The ECR group combined both interventions for 12 weeks. Body weight and food intake were monitored weekly. Post-intervention, liver mass, lipid profiles (TC, TG, LDL-C, HDL-C), hepatic morphology (HE staining), lipid deposition (Oil Red O staining), and protein levels of iNOS, Arg-1, IL-1β, IL-10, NLRP3, Cleaved-Caspase-1, and ASC (Western blot) were analyzed. Macrophage polarization was assessed via immunofluorescence (F4/80, CD86, CD206). Data were analyzed using one-way ANOVA (significance levels: *p < 0.05, **p < 0.01) (1). CR, AE, and ECR groups exhibited significantly lower body weight than CON, with ECR showing the most pronounced reduction (p < 0.05). (2) ECR significantly reduced TC and LDL-C levels compared to CON (p < 0.05). (3) All interventions improved hepatic histology and lowered NAFLD activity scores (NAS), with ECR outperforming AE and CR (p < 0.01). (4) CR and ECR reduced lipid droplet area, with ECR showing superior efficacy (p < 0.01). (5) AE, CR, and ECR suppressed IL-1β and iNOS while elevating IL-10 and Arg-1, with ECR achieving the most significant effects (p < 0.01). NLRP3, Cleaved-Caspase-1, and ASC expression were markedly reduced in ECR versus CON and AE (p < 0.05). (6) ECR decreased F4/80+/CD86+ (M1) co-localization and increased F4/80+/CD206+ (M2) co-localization compared to all groups (p < 0.01). Conclusion: (1) Aerobic exercise primarily induces M2 polarization and anti-inflammatory cytokine upregulation, while caloric restriction suppresses M1 polarization and pro-inflammatory factors. The combined intervention demonstrated superior effects by integrating both mechanisms. (2) NLRP3 inflammasome inhibition correlates with improved macrophage polarization, with the combined intervention exerting stronger suppression on NLRP3 pathway proteins than individual interventions.
Wang et al. (Thu,) studied this question.