Physical fitness status modulates the inflammatory proteins in peripheral blood and circulating monocytes: role of PPAR-gamma

Abstract

The aim of this study was to analyze the metabolic and molecular profile according to physical fitness status (Low or High VO_2max) and its impacts on peripheral and cellular inflammatory responses in healthy men. First (Phase I), inflammatory profile (TNF-α, IL-6, IL-10) was analyzed at baseline and post-acute exercise sessions performed at low (< 60% VO_2max) and high (> 90% VO_2max) intensities considering the individual endotoxin concentrations. Next (Phase II), monocyte cell cultures were treated with LPS alone or associated with Rosiglitazone (PPAR-γ agonist drug) to analyze cytokine production and gene expression. Monocyte subsets were also evaluated by flow cytometry. A positive relationship was observed between LPS concentrations and oxygen uptake (VO_2max) (r = 0.368; p = 0.007); however, in the post-exercise an inverse correlation was found between LPS variation (Δ%) and VO_2max (r = -0.385; p = 0.004). With the low-intensity exercise session, there was inverse correlation between LPS and IL-6 concentrations post-exercise (r = -0.505; p = 0.046) and a positive correlation with IL-10 in the recovery (1 h post) (r = 0.567; p = 0.011), whereas with the high-intensity exercise an inverse correlation was observed with IL-6 at pre-exercise (r = -0.621; p = 0.013) and recovery (r = -0.574; p = 0.016). When monocyte cells were treated with LPS, High VO_2max individuals showed higher PPAR-γ gene expression whereas Low VO_2max individuals displayed higher IL-10 production. Additionally, higher TLR-4, IKK1, and PGC-1α gene expression were observed in the High VO_2max group than Low VO_2max individuals. In conclusion, even with elevated endotoxemia, individuals with High VO_2max exhibited higher IL-6 concentration in peripheral blood post-acute aerobic exercise and lower IL-10 concentration during recovery (1 h post-exercise). The anti-inflammatory effects linked with exercise training and physical fitness status may be explained by a greater gene expression of IKK1, TLR-4, and PGC-1α, displaying an extremely efficient cellular framework for the PPAR-γ responses.

Figure 1

Relationship between LPS concentration (absolute and relative variation) and physical fitness level, represented by VO_2max, at baseline (A, B) and immediately post exercise-session (C, D), independently of exercise intensities (all N = 28 subjects; < LPS N = 14; > LPS N = 14). (A), (C) represent Spearman's correlation with significance established at 5%; (B), (D) represent Mann–Whitney test expressing the results in median and interquartile range being the Y-axis represented by maximal oxygen uptake and X-axis represented by LPS initial concentration or variation post-exercise.

Figure 2

Relationship between relative variation in LPS (percentage difference between the pre and immediately post-exercise concentration values) and physical fitness status, represented by VO_2max, according to exercise sessions performed at low and high intensities (all N = 28 subjects; < LPS N = 14; > LPS N = 14). (A), (B) represent Spearman's correlation with significance established at 5%.

Figure 3

Relative Peroxisome proliferator-activated receptor gamma (PPAR-γ) gene expression in monocytes cell culture treated with LPS ([100 ng/mL]) and without stimulation (control) of individuals classified as Low (N = 6) or High (N = 6) VO_2max. (*)Significant difference between groups (p < 0.05).

Figure 4

Monocyte population in peripheral blood mononuclear cells (PBMC) of individuals classified as Low (N = 11) or High (N = 11) VO_2max. The data are showing in relative expression (percentage of expression) according to the subpopulation.

Figure 5

Cytokine release in monocyte cell culture incubated for 24 h with ( +) or without (−) LPS and Rosiglitazone (Low VO_2max N = 11 or High VO_2max N = 11). Values are expressed as mean ± standard deviation. *Group X Treatment interaction, #Difference within the group between the treatments. Dashed line represents the control group (without stimuli) according to groups. Significance value adopted was 5%.

Figure 6

Relative gene expression of monocyte cell culture incubated for 24 h with ( +) or without (-) LPS and Rosiglitazone (Low VO_2max N = 6 or High VO_2max N = 6). Values expressed as mean ± standard deviation. Letter = difference of condition (treatment) independent of the group (physical fitness status) and Symbols = difference of condition (treatment) dependent of the group (physical fitness status).^aDifferent from control, ^bDifferent from LPS, ^cDifferent from LPS + Rosiglitazone, *Group effect, #Group X Treatment interaction, $Difference within the group between the treatments. Dashed line represents the control group (without stimuli) according to groups. Significance value adopted was 5%.

Figure 7

Conclusion diagram of the experiments and results.