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Recent studies in aging suggest that oral supplementation with the natural polyamine spermidine has a cardioprotective effect. Here, the hypothesis was tested that spermidine or voluntary activity alone or in combination protect the heart from adverse effects induced by obesity. Therefore, C57Bl\/6 mice (<jats:italic>n<\/jats:italic>\u2009=\u20098\u201310 per group) were subjected to control or high fat diet (HFD) and were left untreated, or either received spermidine via drinking water or were voluntarily active or both. After 30\u00a0weeks, the mice were killed and the left ventricle of the hearts was processed for light and electron microscopy. Design-based stereology was used to estimate parameters of hypertrophy, fibrosis, and lipid accumulation. HFD induced cardiac hypertrophy as demonstrated by higher volumes of the left ventricle, cardiomyocytes, interstitium, myofibrils and cardiomyocyte mitochondria. These changes were not influenced by spermidine or voluntary activity. HFD also induced myocardial fibrosis and accumulation of lipid droplets within cardiomyocytes. These HFD effects were enhanced in spermidine treated animals but not in voluntarily active mice. This was even the case in voluntarily active mice that received spermidine. In conclusion, the data confirm the induction of left ventricular hypertrophy by high-fat diet and suggest that\u2014under high fat diet\u2014spermidine enhances cardiomyocyte lipid accumulation and interstitial fibrosis which is counteracted by voluntary activity.<\/jats:p>","DOI":"10.1007\/s00418-020-01926-1","type":"journal-article","created":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T13:03:43Z","timestamp":1611147823000},"page":"75-88","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Voluntary activity reverses spermidine-induced myocardial fibrosis and lipid accumulation in the obese male mouse"],"prefix":"10.1007","volume":"155","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7827-4867","authenticated-orcid":false,"given":"Christian","family":"M\u00fchlfeld","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clara","family":"Pfeiffer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanessa","family":"Schneider","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melanie","family":"Bornemann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Schipke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,10,27]]},"reference":[{"key":"1926_CR1","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1152\/physrev.00017.2007","volume":"88","author":"ED Abel","year":"2008","unstructured":"Abel ED, Litwin SE, Sweeney G (2008) Cardiac remodeling in obesity. 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