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Physical exercise reduces the expression of RANTES and its CCR5 receptor in the adipose tissue of obese humans.

Baturcam E, Abubaker J, Tiss A, Abu-Farha M, Khadir A, Al-Ghimlas F, Al-Khairi I, Cherian P, Elkum N, Hammad M, John J, Kavalakatt S, Lehe C, Warsame S, Behbehani K, Dermime S, Dehbi M - Mediators Inflamm. (2014)

Bottom Line: Fifty-seven adult nondiabetic subjects (17 lean and 40 obese) were enrolled in a 3-month supervised physical exercise.Physical exercise significantly reduced the expression of both RANTES and CCR5 (P < 0.05) in the adipose tissue of obese individuals with a concomitant decrease in the levels of the inflammatory markers TNF- α , IL-6, and P-JNK.Circulating RANTES correlated negatively with anti-inflammatory IL-1 ra (P = 0.001) and positively with proinflammatory IP-10 and TBARS levels (P < 0.05).

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Research, Dasman Diabetes Institute, 1180 Dasman, Kuwait ; Queensland Children's Medical Research Institute, University of Queensland, Brisbane, QLD 4029, Australia.

ABSTRACT
RANTES and its CCR5 receptor trigger inflammation and its progression to insulin resistance in obese. In the present study, we investigated for the first time the effect of physical exercise on the expression of RANTES and CCR5 in obese humans. Fifty-seven adult nondiabetic subjects (17 lean and 40 obese) were enrolled in a 3-month supervised physical exercise. RANTES and CCR5 expressions were measured in PBMCs and subcutaneous adipose tissue before and after exercise. Circulating plasma levels of RANTES were also investigated. There was a significant increase in RANTES and CCR5 expression in the subcutaneous adipose tissue of obese compared to lean. In PBMCs, however, while the levels of RANTES mRNA and protein were comparable between both groups, CCR5 mRNA was downregulated in obese subjects (P < 0.05). Physical exercise significantly reduced the expression of both RANTES and CCR5 (P < 0.05) in the adipose tissue of obese individuals with a concomitant decrease in the levels of the inflammatory markers TNF- α , IL-6, and P-JNK. Circulating RANTES correlated negatively with anti-inflammatory IL-1 ra (P = 0.001) and positively with proinflammatory IP-10 and TBARS levels (P < 0.05). Therefore, physical exercise may provide an effective approach for combating the deleterious effects associated with obesity through RANTES signaling in the adipose tissue.

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Correlation analysis of circulating RANTES with key inflammatory makers. In a mixed population of lean (n = 17) and obese (n = 40), circulating RANTES correlated negatively with the IL-1ra levels and positively with IP-10 chemokine levels and TBARS activity. Correlations were assessed using Spearman's rank correlation coefficient.
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fig1: Correlation analysis of circulating RANTES with key inflammatory makers. In a mixed population of lean (n = 17) and obese (n = 40), circulating RANTES correlated negatively with the IL-1ra levels and positively with IP-10 chemokine levels and TBARS activity. Correlations were assessed using Spearman's rank correlation coefficient.

Mentions: In agreement with our recent investigation [38], obese subjects had higher levels of RANTES in the circulation that correlated negatively with IL-1ra (r2 = 0.42; P = 0.001) and positively with IP-10 (r2 = 0.31; P = 0.02) and TBARS levels (r2 = 0.29; P = 0.03) (Figure 1(a)). To investigate the endogenous expression of RANTES between the two groups at the protein level, we determined its expression in PBMCs and adipose tissue by western blot, flow cytometry, and immunohistochemistry (IHC). As shown in Figure 2(a), there was no difference in the expression of RANTES protein in PBMCs between lean and obese subjects (n = 3 for each group). Consistent with this finding, flow cytometry indicated that RANTES levels were comparable between lean and obese subjects (n = 3 for each group) in both monocytes and lymphocytes (Figure 2(b)). By contrast to PBMCs, the expression of RANTES protein in the adipose tissue as monitored by IHC studies was significantly higher in obese (n = 11) compared to lean (n = 7) subjects (P = 0.01; Figure 2(c)). The differential expression of RANTES between PBMCs and adipose tissue in lean and obese subjects was also confirmed at the mRNA level by using quantitative real-time PCR (qRT-PCR) and the results are displayed in Figures 2(d) and 2(e). Accordingly, there was no change in RANTES mRNA levels in PBMCs from lean and obese subjects (n = 10 for both lean and obese, Figure 2(d)), whereas the levels of RANTES mRNA in the adipose tissue were significantly higher in obese (n = 11) compared to lean (n = 7) subjects (P = 0.02, Figure 2(e)). Under the same conditions, the endogenous expression of the two key inflammatory markers TNF-α and IL-6 in the adipose tissue were significantly increased in obese subjects both at the protein level (P < 0.05, Figure 2(f)) and mRNA level (P < 0.05, Figure 2(g)).


Physical exercise reduces the expression of RANTES and its CCR5 receptor in the adipose tissue of obese humans.

Baturcam E, Abubaker J, Tiss A, Abu-Farha M, Khadir A, Al-Ghimlas F, Al-Khairi I, Cherian P, Elkum N, Hammad M, John J, Kavalakatt S, Lehe C, Warsame S, Behbehani K, Dermime S, Dehbi M - Mediators Inflamm. (2014)

Correlation analysis of circulating RANTES with key inflammatory makers. In a mixed population of lean (n = 17) and obese (n = 40), circulating RANTES correlated negatively with the IL-1ra levels and positively with IP-10 chemokine levels and TBARS activity. Correlations were assessed using Spearman's rank correlation coefficient.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4016945&req=5

fig1: Correlation analysis of circulating RANTES with key inflammatory makers. In a mixed population of lean (n = 17) and obese (n = 40), circulating RANTES correlated negatively with the IL-1ra levels and positively with IP-10 chemokine levels and TBARS activity. Correlations were assessed using Spearman's rank correlation coefficient.
Mentions: In agreement with our recent investigation [38], obese subjects had higher levels of RANTES in the circulation that correlated negatively with IL-1ra (r2 = 0.42; P = 0.001) and positively with IP-10 (r2 = 0.31; P = 0.02) and TBARS levels (r2 = 0.29; P = 0.03) (Figure 1(a)). To investigate the endogenous expression of RANTES between the two groups at the protein level, we determined its expression in PBMCs and adipose tissue by western blot, flow cytometry, and immunohistochemistry (IHC). As shown in Figure 2(a), there was no difference in the expression of RANTES protein in PBMCs between lean and obese subjects (n = 3 for each group). Consistent with this finding, flow cytometry indicated that RANTES levels were comparable between lean and obese subjects (n = 3 for each group) in both monocytes and lymphocytes (Figure 2(b)). By contrast to PBMCs, the expression of RANTES protein in the adipose tissue as monitored by IHC studies was significantly higher in obese (n = 11) compared to lean (n = 7) subjects (P = 0.01; Figure 2(c)). The differential expression of RANTES between PBMCs and adipose tissue in lean and obese subjects was also confirmed at the mRNA level by using quantitative real-time PCR (qRT-PCR) and the results are displayed in Figures 2(d) and 2(e). Accordingly, there was no change in RANTES mRNA levels in PBMCs from lean and obese subjects (n = 10 for both lean and obese, Figure 2(d)), whereas the levels of RANTES mRNA in the adipose tissue were significantly higher in obese (n = 11) compared to lean (n = 7) subjects (P = 0.02, Figure 2(e)). Under the same conditions, the endogenous expression of the two key inflammatory markers TNF-α and IL-6 in the adipose tissue were significantly increased in obese subjects both at the protein level (P < 0.05, Figure 2(f)) and mRNA level (P < 0.05, Figure 2(g)).

Bottom Line: Fifty-seven adult nondiabetic subjects (17 lean and 40 obese) were enrolled in a 3-month supervised physical exercise.Physical exercise significantly reduced the expression of both RANTES and CCR5 (P < 0.05) in the adipose tissue of obese individuals with a concomitant decrease in the levels of the inflammatory markers TNF- α , IL-6, and P-JNK.Circulating RANTES correlated negatively with anti-inflammatory IL-1 ra (P = 0.001) and positively with proinflammatory IP-10 and TBARS levels (P < 0.05).

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Research, Dasman Diabetes Institute, 1180 Dasman, Kuwait ; Queensland Children's Medical Research Institute, University of Queensland, Brisbane, QLD 4029, Australia.

ABSTRACT
RANTES and its CCR5 receptor trigger inflammation and its progression to insulin resistance in obese. In the present study, we investigated for the first time the effect of physical exercise on the expression of RANTES and CCR5 in obese humans. Fifty-seven adult nondiabetic subjects (17 lean and 40 obese) were enrolled in a 3-month supervised physical exercise. RANTES and CCR5 expressions were measured in PBMCs and subcutaneous adipose tissue before and after exercise. Circulating plasma levels of RANTES were also investigated. There was a significant increase in RANTES and CCR5 expression in the subcutaneous adipose tissue of obese compared to lean. In PBMCs, however, while the levels of RANTES mRNA and protein were comparable between both groups, CCR5 mRNA was downregulated in obese subjects (P < 0.05). Physical exercise significantly reduced the expression of both RANTES and CCR5 (P < 0.05) in the adipose tissue of obese individuals with a concomitant decrease in the levels of the inflammatory markers TNF- α , IL-6, and P-JNK. Circulating RANTES correlated negatively with anti-inflammatory IL-1 ra (P = 0.001) and positively with proinflammatory IP-10 and TBARS levels (P < 0.05). Therefore, physical exercise may provide an effective approach for combating the deleterious effects associated with obesity through RANTES signaling in the adipose tissue.

Show MeSH
Related in: MedlinePlus