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We previously reported that medium-chain fatty acids (MCFAs) improve cancer-induced myocardial damage but did not evaluate the differences in effect according to MCFA type. Therefore, this study investigated the role of inflammatory cytokines in cancer-induced myocardial damage and the effects of three types of MCFAs (caprylic acid [C8], capric acid [C10], and lauric acid [C12]). In a mouse model, the C8 diet showed a greater effect on improving myocardial damage compared with C10 and C12 diets. Myocardial tubes differentiated from H9C2 cardiomyoblasts demonstrated increased mitochondrial oxidative stress, decreased membrane potential and mitochondrial volume, and inhibited myocardial tube differentiation following treatment with high-mobility group box-1 (HMGB1) but not interleukin-6 and tumor necrosis factor-\u03b1 cytokines. However, HMGB1 treatment combined with C8 improved HMGB1-induced mitochondrial damage, enhanced autophagy, and increased mitochondrial biogenesis and maturation. However, these effects were only partial when combined with beta-hydroxybutyrate, a C8 metabolite. Thus, HMGB1 may play an important role in cancer-related myocardial damage. C8 counteracts HMGB1\u2019s effects and improves cancer-related myocardial damage. Further clinical studies are required to investigate the effects of C8.<\/jats:p>","DOI":"10.3390\/ijms25158081","type":"journal-article","created":{"date-parts":[[2024,7,24]],"date-time":"2024-07-24T15:47:32Z","timestamp":1721836052000},"page":"8081","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Caprylic Acid Inhibits High Mobility Group Box-1-Induced Mitochondrial Damage in Myocardial Tubes"],"prefix":"10.3390","volume":"25","author":[{"given":"Shota","family":"Nukaga","sequence":"first","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rina","family":"Fujiwara-Tani","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6517-8420","authenticated-orcid":false,"given":"Ryoichi","family":"Nishida","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Miyagawa","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei","family":"Goto","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isao","family":"Kawahara","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chie","family":"Nakashima","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyomu","family":"Fujii","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiko","family":"Ogata","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Ohmori","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2298-8825","authenticated-orcid":false,"given":"Hiroki","family":"Kuniyasu","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,24]]},"reference":[{"key":"ref_1","first-page":"91","article-title":"Increased risk of alteration of nutritional status in hospitalized elderly patients with advanced cancer","volume":"10","author":"Paillaud","year":"2006","journal-title":"J. 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