Low-intensity exercise enhances expression of markers of alternative activation in circulating leukocytes: Roles of PPARy and Th2 cytokines
Roberts, Aled W.
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Objective: Pharmacological activation of the nuclear receptor PPAR is linked to numerous beneficial effects in the contexts of inflammation, lipid homeostasis, Type-2 Diabetes (T2D) and atherosclerosis. These beneficial effects include priming of circulating monocytes for differentiation towards an 'alternative' anti-inflammatory M2 macrophage phenotype. As we have recently shown that participation in low-intensity exercise increases PPAR expression and activity in leukocytes from previously sedentary individuals, we aimed to elucidate whether low-intensity exercise elicited a pattern of gene expression similar to that reported for M2 monocyte-macrophage differentiation. Methods: 17 sedentary individuals undertook an 8-week low-intensity exercise programme (walking 10,000 steps/day, three times/week). Changes in expression of PPARs and the PPAR co-activators PGC- 1 and PGC-1 ; Th2 (IL-4; IL-10) and Th1 (IL-6) cytokines; and markers for the M2 (AMAC1, CD14, MR, IL-4) and the 'classical' pro-inflammatory M1 (MCP-1, TNF , IL-6) phenotypes, were determined using RT-PCR (to assess leukocyte mRNA expression) and ELISA (to assess plasma cytokine levels). Results: Exercise was associated with upregulation of M2 markers, PGC-1 and PGC-1 , and with downregulation of M1 markers. Moreover, plasma levels of Th2 cytokines increased after exercise, while those of Th1 cytokines decreased. However, other PPARs (PPAR ; PPAR / ) did not undergo marked exerciseinduced activation or upregulation. Thus, participation in low-intensity exercise may prime monocytes for differentiation towards an M2 macrophage phenotype via PPAR /PGC-1 / . Conclusion: Given the similarities between these effects and pharmacologically induced M2 polarisation, we propose that exercise-induced PPAR /PGC-1 / -mediated M2 polarisation may constitute a novel anti-inflammatory benefit of low-intensity exercise. © 2010 Elsevier Ireland Ltd. All rights reserved.
Yakeu, G., Butcher, L., Isa, S., Webb, R., Roberts, A.W., Thomas, A.W., Backx, K., James, P.E. and Morris, K. (2010) 'Low-intensity exercise enhances expression of markers of alternative activation in circulating leukocytes: roles of PPARγ and Th2 cytokines', Atherosclerosis, 212(2), pp.668-673.
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Yakeu, Gertrude (University of WalesCardiff School of Health Sciences, 2010)Pharmacological activation of the nuclear receptor PPARγ enhances differentiation of circulating monocytes towards an alternative anti-inflammatory M2 phenotype, linked to atherosclerosis and its cardiovascular complications. ...
Yakeu, Gertrude (Cardiff Metropolitan University, 2010)Pharmacological activation of the nuclear receptor PPARγ enhances differentiation of circulating monocytes towards an alternative anti-inflammatory M2 phenotype, linked to atherosclerosis and its cardiovascular complications. ...
Butcher, Lee; Thomas, Andrew; Backx, Karianne; Roberts, Aled W.; Webb, Richard; Morris, Keith (American College of Sports Medicine, 2008)Introduction: An important mechanism by which physical activity reduces the risk of cardiovascular disease is through regulating plasma lipids. We investigated whether low-intensity exercise modulates lipid metabolism and ...