{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T12:30:40Z","timestamp":1774269040480,"version":"3.50.1"},"reference-count":94,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T00:00:00Z","timestamp":1715126400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Swiss National Research Foundation","award":["CRSK-3_220309"],"award-info":[{"award-number":["CRSK-3_220309"]}]},{"name":"Research Fund of the University of Basel for Excellent Junior Researchers","award":["U.360.0002"],"award-info":[{"award-number":["U.360.0002"]}]},{"DOI":"10.13039\/501100022796","name":"Swiss Life Jubilee Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100022796","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Introduction<\/jats:title>\n<jats:p>Evidence indicates that sphingolipid accumulation drives complex molecular alterations promoting cardiometabolic diseases. Clinically, it was shown that sphingolipids predict cardiometabolic risk independently of and beyond traditional biomarkers such as low-density lipoprotein cholesterol. To date, little is known about therapeutic modalities to lower sphingolipid levels. Exercise, a powerful means to prevent and treat cardiometabolic diseases, is a promising modality to mitigate sphingolipid levels in a cost-effective, safe, and patient-empowering manner.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>This randomised controlled trial will explore whether and to what extent an 8-week fitness-enhancing training programme can lower serum sphingolipid levels of middle-aged adults at elevated cardiometabolic risk (n = 98, 50% females). The exercise intervention will consist of supervised high-intensity interval training (three sessions weekly), while the control group will receive physical activity counselling based on current guidelines. Blood will be sampled early in the morning in a fasted state before and after the 8-week programme. Participants will be provided with individualised, pre-packaged meals for the two days preceding blood sampling to minimise potential confounding. An \u2019omic-scale sphingolipid profiling, using high-coverage reversed-phase liquid chromatography coupled to tandem mass spectrometry, will be applied to capture the circulating sphingolipidome. Maximal cardiopulmonary exercise tests will be performed before and after the 8-week programme to assess patient fitness changes. Cholesterol, triglycerides, glycated haemoglobin, the homeostatic model assessment for insulin resistance, static retinal vessel analysis, flow-mediated dilatation, and strain analysis of the heart cavities will also be assessed pre- and post-intervention. This study shall inform whether and to what extent exercise can be used as an evidence-based treatment to lower circulating sphingolipid levels.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Trial registration<\/jats:title>\n<jats:p>The trial was registered on <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.clinicaltrials.gov\/\" xlink:type=\"simple\">www.clinicaltrials.gov<\/jats:ext-link> (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT06024291\" xlink:type=\"simple\">NCT06024291<\/jats:ext-link>) on August 28, 2023.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0302477","type":"journal-article","created":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T17:30:01Z","timestamp":1715189401000},"page":"e0302477","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effect of an eight-week high-intensity interval training programme on circulating sphingolipid levels in middle-aged adults at elevated cardiometabolic risk (SphingoFIT)\u2014Protocol for a randomised controlled exercise trial"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2380-105X","authenticated-orcid":true,"given":"Justin","family":"Carrard","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel","family":"Hofer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luisa","family":"Prechtl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Fleischlin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel","family":"Huber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hector","family":"Gallart-Ayala","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tony","family":"Teav","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9028-7110","authenticated-orcid":true,"given":"Denis","family":"Infanger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"H\u00f6chsmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karsten","family":"Koehler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timo","family":"Hinrichs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5501-4205","authenticated-orcid":true,"given":"Henner","family":"Hanssen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julijana","family":"Ivanisevic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arno","family":"Schmidt-Trucks\u00e4ss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,5,8]]},"reference":[{"issue":"9859","key":"pone.0302477.ref001","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1016\/S0140-6736(12)61728-0","article-title":"Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010","volume":"380","author":"R Lozano","year":"2012","journal-title":"The Lancet"},{"key":"pone.0302477.ref002","unstructured":"Global, regional, and national disability-adjusted life years (DALYs) for diseases and injuries and healthy life expectancy (HALE), 1990 to 2019: quantifying the epidemiological transition. 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