Cardiometabolic and immune response to exercise training in patients with metabolic syndrome: retrospective analysis of two randomized clinical trials

Background Metabolic syndrome (MetS) is defined by the presence of central obesity plus >= two metabolic/cardiovascular risk factors (RF), with inflammation being a major disease-driving mechanism. Structured endurance exercise training (ET) may positively affect these traits, as well as cardiorespiratory fitness (VO(2)peak). Aims We explore individual ET-mediated improvements of MetS-associated RF in relation to improvements in VO(2)peak and inflammatory profile. Methods MetS patients from two randomized controlled trials, ExMET (n = 24) and OptimEx (n = 34), had performed 4- or 3-months supervised ET programs according to the respective trial protocol. VO2peak, MetS-defining RFs (both RCTs), broad blood leukocyte profile, cytokines and plasma proteins (ExMET only) were assessed at baseline and follow-up. Intra-individual changes in RFs were analysed for both trials separately using non-parametric approaches. Associations between changes in each RF over the exercise period (n-fold of baseline values) were correlated using a non-parametrical approach (Spearman). RF clustering was explored by uniform manifold approximation and projection (UMAP) and changes in RF depending on other RF or exercise parameters were explored by recursive partitioning. Results Four months of ET reduced circulating leukocyte counts (63.5% of baseline, P = 8.0e-6), especially effector subtypes. ET response of MetS-associated RFs differed depending on patients' individual RF constellation, but was not associated with individual change in VO(2)peak. Blood pressure lowering depended on cumulative exercise duration (ExMET: >= 102 min per week; OptimEx-MetS: >= 38 min per session) and baseline triglyceride levels (ExMET: <150 mg/dl; OptimEx-MetS: <174.8 mg/dl). Neuropilin-1 plasma levels were inversely associated with fasting plasma triglycerides (R: -0.4, P = 0.004) and changes of both parameters during the ET phase were inversely correlated (R: -0.7, P = 0.0001). Conclusions ET significantly lowered effector leukocyte blood counts. The improvement of MetS-associated cardiovascular RFs depended on individual basal RF profile and exercise duration but was not associated with exercise-mediated increase in VO(2)peak. Neuropilin-1 may be linked to exercise-mediated triglyceride lowering.