期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 21, 页码 -出版社
MDPI
DOI: 10.3390/ijms222111497
关键词
peroxisome-proliferator-activated receptor; fatty acid oxidation; doping control; regulatory T cells; inflammation; exercise
资金
- INSERM
- Universite Cote d'Azur
- Fondation pour la Recherche Medicale (FRM) [DRM20101220437]
- Agence Francaise de Lutte contre le Dopage (AFLD) [R17020AA]
Studies have shown that PPAR beta/delta activation increases the FAO potential in human and mouse T cells, as well as in mouse secondary lymphoid organs. It also induces Treg polarization in human primary T cells. However, the signature of PPAR beta/delta activation in mouse blood T cells may be masked by exercise training.
Synthetic ligands of peroxisome-proliferator-activated receptor beta/delta (PPAR beta /delta) are being used as performance-enhancing drugs by athletes. Since we previously showed that PPAR beta /delta activation affects T cell biology, we wanted to investigate whether a specific blood T cell signature could be employed as a method to detect the use of PPAR beta /delta agonists. We analyzed in primary human T cells the in vitro effect of PPAR beta /delta activation on fatty acid oxidation (FAO) and on their differentiation into regulatory T cells (Tregs). Furthermore, we conducted studies in mice assigned to groups according to an 8-week exercise training program and/or a 6-week treatment with 3 mg/kg/day of GW0742, a PPAR beta /delta agonist, in order to (1) determine the immune impact of the treatment on secondary lymphoid organs and to (2) validate a blood signature. Our results show that PPAR beta /delta activation increases FAO potential in human and mouse T cells and mouse secondary lymphoid organs. This was accompanied by increased Treg polarization of human primary T cells. Moreover, Treg prevalence in mouse lymph nodes was increased when PPAR beta /delta activation was combined with exercise training. Lastly, PPAR beta /delta activation increased FAO potential in mouse blood T cells. Unfortunately, this signature was masked by training in mice. In conclusion, beyond the fact that it is unlikely that this signature could be used as a doping-control strategy, our results suggest that the use of PPAR beta /delta agonists could have potential detrimental immune effects that may not be detectable in blood samples.
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