Moderate-intensity exercise alters markers of alternative activation in circulating monocytes in females: a putative role for PPARγ

Abstract

PurposeMonocytes may be primed towards differentiation into classically activated M1 macrophages or alternatively activated M2 macrophages. M1 macrophages greatly contribute to the inflammation which promotes insulin resistance, whereas M2 macrophages resolve inflammation. We have previously shown that exercise increases M2 marker expression in mixed mononuclear cells, possibly via activation of the nuclear transcription factor PPARγ. However, these effects have not been demonstrated specifically within monocytes. Thus, we aimed to investigate whether moderate-intensity exercise elicited similar effects on monocytic M1/M2 marker expression and PPARγ activity to those reported previously in mononuclear cells, so as to further elucidate the mechanisms by which exercise may alter inflammatory status and, accordingly, prevent insulin resistance.Methods/results19 sedentary females completed an 8 week moderate-intensity exercise programme (walking 45 min, thrice weekly). Monocytes were isolated from blood via immunomagnetic separation; monocyte expression of M2 markers (Dectin-1: 2.6 ± 1.9-fold; IL-10: 3.0 ± 2.8-fold) significantly increased, whilst the expression of the M1 marker MCP-1 significantly decreased (0.83 ± 0.2 cf. basal), over the duration of the programme. Serum PPARγ activity levels and PPARγ target-genes (CD36: 1.9 ± 1.5-fold; LXRα: 5.0 ± 4.7-fold) were significantly increased after the 8 week exercise programme. Associated with these effects were significant improvements in systemic insulin sensitivity (McAuley’s ISI: Δ0.98 M/mU/L cf. basal).ConclusionExercise participation suppressed M1 markers and induced M2 markers in monocytes, potentially via PPARγ-triggered signalling, and these effects may contribute (perhaps via priming of monocytes for differentiation into M2 tissue-macrophages) to improved systemic insulin sensitivity in exercising participants. These findings provide an alternative mechanism by which exercise may exert its anti-inflammatory effects in order to prevent insulin resistance and type 2 diabetes.Electronic supplementary materialThe online version of this article (doi:10.1007/s00421-016-3414-y) contains supplementary material, which is available to authorized users.

Towards a personalised approach in exercise-based cardiovascular rehabilitation: How can translational research help? A ‘call to action’ from the Section on Secondary Prevention and Cardiac Rehabilitation of the European Association of Preventive Cardiology

“…[95][96][97] This might be attributed to acute and chronic effects: strain and acute release of pro-inflammatory mediators are associated with SPM release in acute high-intensity exertion, while chronic effects of exercise intervention might be connected to the exercise-mediated shift in macrophage polarization towards the M2-like phenotype. 95,97,98 M2-like macrophages are better suited to perform efferocytosis than the M1-like phenotype and it is during efferocytosis that SPMs are released. 99 Thus, we know that regular exercise is associated with a shift towards the more proresolving macrophage spectrum, as well as higher levels of pro-resolving mediators, but we do not know which exercise parameters (e.g.…”

Exercise effects on perivascular adipose tissue: endocrine and paracrine determinants of vascular function

“…Exercise can be considered an anti‐inflammatory treatment (Ruffino et al ., ). Firstly, exercise decreases body fat and adipocyte hypertrophy.…”

<p>High-Intensity Interval Training Reversed High-Fat Diet–Induced M1-Macrophage Polarization in Rat Adipose Tissue via Inhibition of NOTCH Signaling</p>

“…36 In parallel, Ruffino et al showed that an 8-week walking-intervention program induced M2-biomarker expression in humans. 37 In another study, Kawanishi et al showed that exercise training reduced macrophage clusters in adipose tissue and increased the number of CD8 + T cells in obese mice. 38 It was shown that exercise training in HFD-fed mice also inhibited adipose-tissue inflammation by inhibiting TNFα, TLR4, and the number of F4/80 macrophages.…”