title: Moderate-intensity exercise alters markers of alternative activation in circulating monocytes in females: a putative role for PPARγ.
abstract: OBJECTIVE
  Monocytes 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.
  
  
  RESULTS
  19 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).
  
  
  CONCLUSIONS
  Exercise 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.
authors.affiliation: Centre for Biomedical Science, Cardiff Metropolitan University, Cardiff, CF5 2YB, UK.
authors.forename: J S
authors.initials: JS
authors.lastname: Ruffino
authors.affiliation: College of Medicine, Swansea University, Swansea, SA2 8PP, UK.
authors.forename: N A
authors.initials: NA
authors.lastname: Davies
authors.affiliation: Centre for Endocrine & Diabetes Sciences, Cardiff University School of Medicine, Cardiff, CF14 4YU, UK.
authors.forename: K
authors.initials: K
authors.lastname: Morris
authors.affiliation: Centre for Endocrine & Diabetes Sciences, Cardiff University School of Medicine, Cardiff, CF14 4YU, UK.
authors.forename: M
authors.initials: M
authors.lastname: Ludgate
authors.affiliation: Centre for Endocrine & Diabetes Sciences, Cardiff University School of Medicine, Cardiff, CF14 4YU, UK.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Centre for Biomedical Science, Cardiff Metropolitan University, Cardiff, CF5 2YB, UK.
authors.forename: R
authors.initials: R
authors.lastname: Webb
authors.affiliation: Centre for Biomedical Science, Cardiff Metropolitan University, Cardiff, CF5 2YB, UK. AThomas@cardiffmet.ac.uk.
authors.forename: A W
authors.initials: AW
authors.lastname: Thomas
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D002454:Cell Differentiation / Q000276:immunology; D015444:Exercise / Q000502:physiology*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood / Q000276:immunology*; D009000:Monocytes / Q000145:classification / Q000166:cytology* / Q000276:immunology*; D047495:PPAR gamma / Q000097:blood / Q000276:immunology*; D005082:Physical Exertion / Q000276:immunology*
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D047495:PPAR gamma
keywords: Exercise; Insulin resistance; Monocyte; PPARγ; Polarisation