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The Contributions of Oxidative Stress, Oxidised Lipoproteins and AMPK Towards Exercise-Associated PPARγ Signalling within Human Monocytic Cells.
MedLine Citation:
PMID:  25377300     Owner:  NLM     Status:  Publisher    
ABSTRACT PPARγ is known to be activated via exercise-associated transient increases in oxidative stress. However, the precise mechanism(s) triggering PPARγ activation in monocytes during/following exercise remain to be confirmed. Here, two cohorts of five healthy male individuals undertook exercise bouts (cycling; 70%max; 45min) in the presence/absence of dietary antioxidant supplementation (vitamins C (1000mg/day) and E (400IU/day) for four weeks prior to exercise), and monocytic AMPK/PGC-1α/PPARγ signalling was investigated in samples obtained pre- and up to 24h post-exercise, while THP-1 cells were cultured as an in-vitro monocyte model. In THP-1 cells, AMPKα1 was phosphorylated within 1h of menadione (15μM)-triggered increases in [ROS]cyto, an effect which was followed by upregulation of PPARγ and several of its target genes (PGC-1α, LXRα, ABCA1; 24-72h), with these effects being blunted by co-administration of Vitamin C (62.5μM). Conversely, treatment with oxLDL (1μg/mL; 24-72h), but not non-oxidised LDL, upregulated the above PPARγ-regulated genes without affecting AMPKα1 phosphorylation. In-vivo, dietary antioxidant supplementation (which is known to prevent exercise-triggered increases in oxLDL levels) blunted exercise-associated upregulation of the above PPARγ-regulated genes, but had no effect on exercise-associated transient [ROS]cyto increases, or on AMPK phosphorylation. These data suggest that exercise-associated PPARγ signalling effects appear, at least in monocytes, to be mediated by increased generation of PPARγ ligands via oxidation of lipoproteins (following exercise-associated transient increases in oxidative stress), rather than via [ROS]cyto-mediated AMPK activation. These findings may be of clinical relevance, as PPARγ activation in monocytes is associated with beneficial effects related to Type-2 Diabetes and its cardiovascular complications.
N A Davies; L Watkeys; L Butcher; S Potter; M G Hughes; H Moir; K Morris; A W Thomas; R Webb
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-11-7
Journal Detail:
Title:  Free radical research     Volume:  -     ISSN:  1029-2470     ISO Abbreviation:  Free Radic. Res.     Publication Date:  2014 Nov 
Date Detail:
Created Date:  2014-11-7     Completed Date:  -     Revised Date:  2014-11-8    
Medline Journal Info:
Nlm Unique ID:  9423872     Medline TA:  Free Radic Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  1-32     Citation Subset:  -    
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