{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T18:23:49Z","timestamp":1761157429240,"version":"build-2065373602"},"reference-count":41,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T00:00:00Z","timestamp":1663286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FONDATION DE FRANCE","award":["2008-002688","2012-00029514","2014-00047972"],"award-info":[{"award-number":["2008-002688","2012-00029514","2014-00047972"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Exercise induces cardioprotection against myocardial infarction, despite obesity, by restoring pro-survival pathways and increasing resistance of mitochondrial permeability transition pore (mPTP) opening at reperfusion. Among the mechanisms involved in the inactivation of these pathways, oxysterols appear interesting. Thus, we investigated the influence of regular exercise on the reperfusion injury salvage kinase (RISK) pathway, oxysterols, and mitochondria, in the absence of ischemia-reperfusion. We also studied 7\u03b2-hydroxycholesterol (7\u03b2OH) concentration (mass spectrometry) in human lean and obese subjects. Wild-type (WT) and obese (ob\/ob) mice were assigned to sedentary conditions or regular treadmill exercise. Exercise significantly increased Akt phosphorylation, whereas 7\u03b2OH concentration was reduced. Moreover, exercise induced the translocation of PKC\u03b5 from the cytosol to mitochondria. However, exercise did not affect the calcium concentration required to open mPTP in the mitochondria, neither in WT nor in ob\/ob animals. Finally, human plasma 7\u03b2OH concentration was consistent with observations made in mice. In conclusion, regular exercise enhanced the RISK pathway by increasing kinase phosphorylation and PKC\u03b5 translocation and decreasing 7\u03b2OH concentration. This activation needs the combination with stress conditions, i.e., ischemia-reperfusion, in order to inhibit mPTP opening at the onset of reperfusion. The human findings suggest 7\u03b2OH as a candidate marker for evaluating cardiovascular risk factors in obesity.<\/jats:p>","DOI":"10.3390\/ijms231810840","type":"journal-article","created":{"date-parts":[[2022,9,18]],"date-time":"2022-09-18T23:39:22Z","timestamp":1663544362000},"page":"10840","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cardioprotective Signaling Pathways in Obese Mice Submitted to Regular Exercise: Effect on Oxysterols"],"prefix":"10.3390","volume":"23","author":[{"given":"Caroline","family":"Barau","sequence":"first","affiliation":[{"name":"Inserm U955-IMRB, UPEC, Ecole Nationale V\u00e9t\u00e9rinaire d\u2019Alfort, F-94010 Cr\u00e9teil, France"},{"name":"Plateforme de Ressources Biologiques, APHP, H\u00f4pitaux Universitaires Henri Mondor, F-94000 Cr\u00e9teil, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1980-567X","authenticated-orcid":false,"given":"Shirin","family":"Leick","sequence":"additional","affiliation":[{"name":"Inserm U955-IMRB, UPEC, Ecole Nationale V\u00e9t\u00e9rinaire d\u2019Alfort, F-94010 Cr\u00e9teil, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"Caccia","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS\u2014Istituto Neurologico Carlo Besta, 20131 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lolita","family":"Portal","sequence":"additional","affiliation":[{"name":"Inserm U955-IMRB, UPEC, Ecole Nationale V\u00e9t\u00e9rinaire d\u2019Alfort, F-94010 Cr\u00e9teil, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8954-0366","authenticated-orcid":false,"given":"Valerio","family":"Leoni","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Biochemistry, Hospital Pius XI of Desio, ASST-Brianza, University of Milano-Bicocca, 20126 Monza, Italy"},{"name":"Department of Medicine and Surgery, University of Milano-Bicocca, 20126 Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe","family":"Le Corvoisier","sequence":"additional","affiliation":[{"name":"Inserm U955-IMRB, UPEC, Ecole Nationale V\u00e9t\u00e9rinaire d\u2019Alfort, F-94010 Cr\u00e9teil, France"},{"name":"INSERM CIC 1430, APHP, H\u00f4pitaux Universitaires Henri Mondor, F-94000 Cr\u00e9teil, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Didier","family":"Morin","sequence":"additional","affiliation":[{"name":"Inserm U955-IMRB, UPEC, Ecole Nationale V\u00e9t\u00e9rinaire d\u2019Alfort, F-94010 Cr\u00e9teil, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bijan","family":"Ghaleh","sequence":"additional","affiliation":[{"name":"Inserm U955-IMRB, UPEC, Ecole Nationale V\u00e9t\u00e9rinaire d\u2019Alfort, F-94010 Cr\u00e9teil, France"},{"name":"Plateforme de Ressources Biologiques, APHP, H\u00f4pitaux Universitaires Henri Mondor, F-94000 Cr\u00e9teil, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7561-9869","authenticated-orcid":false,"given":"Sandrine","family":"Pons","sequence":"additional","affiliation":[{"name":"Inserm U955-IMRB, UPEC, Ecole Nationale V\u00e9t\u00e9rinaire d\u2019Alfort, F-94010 Cr\u00e9teil, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/sj.bjp.0706833","article-title":"Obesity\u2014A risk factor or a RISK factor for myocardial infarction?","volume":"149","author":"Heusch","year":"2006","journal-title":"Br. 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