Gene Doping with Peroxisome-Proliferator-Activated Receptor Beta/Delta Agonists Alters Immunity but Exercise Training Mitigates the Detection of Effects in Blood Samples

Synthetic ligands of peroxisome-proliferator-activated receptor beta/delta (PPARβ/δ) are being used as performance-enhancing drugs by athletes. Since we previously showed that PPARβ/δ activation affects T cell biology, we wanted to investigate whether a specific blood T cell signature could be emplo...

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Autores principales:	Brigitte Sibille, Isabelle Mothe-Satney, Gwenaëlle Le Menn, Doriane Lepouse, Sébastien Le Garf, Elodie Baudoin, Joseph Murdaca, Claudine Moratal, Noura Lamghari, Giulia Chinetti, Jaap G. Neels, Anne-Sophie Rousseau
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	peroxisome-proliferator-activated receptor fatty acid oxidation doping control regulatory T cells inflammation exercise Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/3ef7540ca4824c7e8d9762079a644faa
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spelling	oai:doaj.org-article:3ef7540ca4824c7e8d9762079a644faa2021-11-11T16:57:39ZGene Doping with Peroxisome-Proliferator-Activated Receptor Beta/Delta Agonists Alters Immunity but Exercise Training Mitigates the Detection of Effects in Blood Samples10.3390/ijms2221114971422-00671661-6596https://doaj.org/article/3ef7540ca4824c7e8d9762079a644faa2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11497https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Synthetic ligands of peroxisome-proliferator-activated receptor beta/delta (PPARβ/δ) are being used as performance-enhancing drugs by athletes. Since we previously showed that PPARβ/δ 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 PPARβ/δ agonists. We analyzed in primary human T cells the in vitro effect of PPARβ/δ 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 PPARβ/δ 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 PPARβ/δ 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 PPARβ/δ activation was combined with exercise training. Lastly, PPARβ/δ 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 PPARβ/δ agonists could have potential detrimental immune effects that may not be detectable in blood samples.Brigitte SibilleIsabelle Mothe-SatneyGwenaëlle Le MennDoriane LepouseSébastien Le GarfElodie BaudoinJoseph MurdacaClaudine MoratalNoura LamghariGiulia ChinettiJaap G. NeelsAnne-Sophie RousseauMDPI AGarticleperoxisome-proliferator-activated receptorfatty acid oxidationdoping controlregulatory T cellsinflammationexerciseBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11497, p 11497 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	peroxisome-proliferator-activated receptor fatty acid oxidation doping control regulatory T cells inflammation exercise Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	peroxisome-proliferator-activated receptor fatty acid oxidation doping control regulatory T cells inflammation exercise Biology (General) QH301-705.5 Chemistry QD1-999 Brigitte Sibille Isabelle Mothe-Satney Gwenaëlle Le Menn Doriane Lepouse Sébastien Le Garf Elodie Baudoin Joseph Murdaca Claudine Moratal Noura Lamghari Giulia Chinetti Jaap G. Neels Anne-Sophie Rousseau Gene Doping with Peroxisome-Proliferator-Activated Receptor Beta/Delta Agonists Alters Immunity but Exercise Training Mitigates the Detection of Effects in Blood Samples
description	Synthetic ligands of peroxisome-proliferator-activated receptor beta/delta (PPARβ/δ) are being used as performance-enhancing drugs by athletes. Since we previously showed that PPARβ/δ 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 PPARβ/δ agonists. We analyzed in primary human T cells the in vitro effect of PPARβ/δ 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 PPARβ/δ 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 PPARβ/δ 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 PPARβ/δ activation was combined with exercise training. Lastly, PPARβ/δ 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 PPARβ/δ agonists could have potential detrimental immune effects that may not be detectable in blood samples.
format	article
author	Brigitte Sibille Isabelle Mothe-Satney Gwenaëlle Le Menn Doriane Lepouse Sébastien Le Garf Elodie Baudoin Joseph Murdaca Claudine Moratal Noura Lamghari Giulia Chinetti Jaap G. Neels Anne-Sophie Rousseau
author_facet	Brigitte Sibille Isabelle Mothe-Satney Gwenaëlle Le Menn Doriane Lepouse Sébastien Le Garf Elodie Baudoin Joseph Murdaca Claudine Moratal Noura Lamghari Giulia Chinetti Jaap G. Neels Anne-Sophie Rousseau
author_sort	Brigitte Sibille
title	Gene Doping with Peroxisome-Proliferator-Activated Receptor Beta/Delta Agonists Alters Immunity but Exercise Training Mitigates the Detection of Effects in Blood Samples
title_short	Gene Doping with Peroxisome-Proliferator-Activated Receptor Beta/Delta Agonists Alters Immunity but Exercise Training Mitigates the Detection of Effects in Blood Samples
title_full	Gene Doping with Peroxisome-Proliferator-Activated Receptor Beta/Delta Agonists Alters Immunity but Exercise Training Mitigates the Detection of Effects in Blood Samples
title_fullStr	Gene Doping with Peroxisome-Proliferator-Activated Receptor Beta/Delta Agonists Alters Immunity but Exercise Training Mitigates the Detection of Effects in Blood Samples
title_full_unstemmed	Gene Doping with Peroxisome-Proliferator-Activated Receptor Beta/Delta Agonists Alters Immunity but Exercise Training Mitigates the Detection of Effects in Blood Samples
title_sort	gene doping with peroxisome-proliferator-activated receptor beta/delta agonists alters immunity but exercise training mitigates the detection of effects in blood samples
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/3ef7540ca4824c7e8d9762079a644faa
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Gene Doping with Peroxisome-Proliferator-Activated Receptor Beta/Delta Agonists Alters Immunity but Exercise Training Mitigates the Detection of Effects in Blood Samples

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