{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T19:22:52Z","timestamp":1790968972788,"version":"4.1.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2018,6,20]],"date-time":"2018-06-20T00:00:00Z","timestamp":1529452800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["#267637"],"award-info":[{"award-number":["#267637"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["#292540"],"award-info":[{"award-number":["#292540"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["#305396"],"award-info":[{"award-number":["#305396"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["#277986"],"award-info":[{"award-number":["#277986"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Sigrid Juselius Foundation"},{"name":"Finnish Foundation for Alcohol Studies"},{"name":"Finnish Cultural Foundation, North Savo Regional Fund"},{"DOI":"10.13039\/501100008397","name":"Finnish Society of Sciences and Letters","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008397","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Heart failure (HF) is associated with drastic changes in metabolism leading to a cardiac energy deficiency well as maladaptive changes in multiple other tissues. It is still unclear which of these changes originates from cardiomyocyte metabolic remodelling or whether they are induced secondarily by systemic factors. Our aim here was to induce cardiac restricted metabolic changes mimicking those seen in HF and to characterize the associated metabolite changes in the heart, circulation, and peripheral tissues.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>We generated a cardiac specific PGC-1\u03b1 knockout mice (KO) to specifically induce metabolic dysregulation typically accompanied by HF and performed a non-targeted LC-MS metabolite profiling analysis of heart, plasma, liver, and skeletal muscle to identify metabolites associated with cardiac specific metabolic remodelling. The KO animals developed a progressive cardiomyopathy with cardiac dilatation leading to fatal HF. At 17\u2009weeks of age, when significant remodelling had occurred but before the onset of HF, isolated PGC-1\u03b1 deficient cardiomyocytes had suppressed glucose and fatty acid oxidation as well as blunted anaerobic metabolism. KO hearts displayed a distinctive metabolite profile with 92 significantly altered molecular features including metabolite changes in energy metabolism, phospholipid metabolism, amino acids, and oxidative stress signalling. Some of the metabolite changes correlated with the specific parameters of cardiac function. We did not observe any significant alterations in the metabolomes of the other measured tissues or in plasma.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Heart specific PGC-1\u03b1 KO induces metabolic, functional, and structural abnormalities leading to dilating cardiomyopathy and HF. The metabolic changes were limited to the cardiac tissue indicating that cardiomyocyte metabolic remodelling is not sufficient to evoke the body wide metabolic alterations usually associated with HF.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvy155","type":"journal-article","created":{"date-parts":[[2018,6,16]],"date-time":"2018-06-16T07:07:22Z","timestamp":1529132842000},"page":"107-118","source":"Crossref","is-referenced-by-count":67,"title":["Heart specific PGC-1\u03b1 deletion identifies metabolome of cardiac restricted metabolic heart failure"],"prefix":"10.1093","volume":"115","author":[{"given":"Olli","family":"K\u00e4rkk\u00e4inen","sequence":"first","affiliation":[{"name":"Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Yliopistonranta 1 C, Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomi","family":"Tuomainen","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Neulaniementie 2, Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maija","family":"Mutikainen","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Neulaniementie 2, Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marko","family":"Lehtonen","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Eastern Finland, Yliopistonranta 1 C, Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge L","family":"Ruas","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Karolinska Institutet, Solnav\u00e4gen 1, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kati","family":"Hanhineva","sequence":"additional","affiliation":[{"name":"Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Yliopistonranta 1 C, Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasi","family":"Tavi","sequence":"additional","affiliation":[{"name":"A.I. 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