Immunomodulatory effects of aerobic training in obesity

Abstract

Introduction: Physical inactivity and obesity are independent risk factors for atherosclerosis. We analyzed the immunomodulatory capacity of 10-week intensified exercise training (ET) in obese and lean athletes. Markers of the innate immune response were investigated in obese (ONE: ET≤40 km/week) and lean athletes (LNE: ET≤40 km/week and LE: ET≥55 km/week).

Methods: Circulating dendritic cells (DC) were analyzed by flow-cytometry for BDCA-1/-2-expression. TLR-2/-4/-7 and MyD88 were analyzed by RT-PCR and Western blot. Circulating oxLDL levels were analyzed by ELISA.

Results: BDCA-1 expression at baseline was lower in ONE compared to both other groups (ONE 0.15%; LNE 0.27%; LE 0.33%; P < .05), but significantly increased in ONE after training (+50%; P < .05). In contrast, BDCA-2 expression at baseline was higher in ONE (ONE 0.25%; LNE 0.11%; LE 0.09%; P < .05) and decreased in ONE after the 10-week training period (-27%; P < .05). Gene activations of TLR-4 and TLR-7 with corresponding protein increase were found for all three groups (P < .01/P < .05) compared to pre training. A reduction of oxLDL levels was seen in ONE (-61%; P < .05).

Conclusions: Intensified exercise induces an increase of BDCA-1+ DCs and TLR-4/-7 in obese athletes. We hereby describe new immune modulatory effects, which-through regular aerobic exercise-modulate innate immunity and pro-inflammatory cytokines in obesity.

Figure 1

Representative FACS scans in PBMC expressing of BDCA-1 (a) and BDCA-2 (b) in LE, LNE, and ONE at baseline and after training. Data presented state the expression of the corresponding receptors in percent. Statistical analysis of the different timepoints (intra group analysis) was performed using the Wilcoxon Test; the comparison of the different groups with each other (inter group analysis) was done by using the Mann-Whitney U Test (*P < .05; n = 15/16/16).

Figure 2

Expression of TLR-2 (a), TLR-4 (b), and TLR-7 (c) by analysis of mRNA levels via RT-PCR. Training-induced changes were analyzed using the delta-delta ct method. Expression of MyD88 (d), TLR-2 (e), TLR-4 (f), and TLR-7 (g) by analyses of protein expression (Western blot of 4 representative examples of the LNE-group). Densitometry analysis (h) found a significant increased expression for TLR-4 and TLR-7. For MyD88 and TLR-2, no significant changes were found. Statistical analysis of the different time-points (intra group-analysis) was performed using the Wilcoxon-Test; the comparison of the different groups with each other (inter group analysis) was done by using the Mann-Whitney U Test (**P < .01; *P < .05; n = 15/16/16 for PCR and n = 8 for Western blot).