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FGF15\/19 mainly targets the liver, but recent studies indicate that it also regulates skeletal muscle mass and adipose tissue plasticity. The aim of this study was to determine the role(s) of the enterokine FGF15\/19 during the development of cardiac hypertrophy. Studies in a cohort of humans suffering from heart failure showed increased circulating levels of FGF19 compared with control individuals. We found that mice lacking FGF15 did not develop cardiac hypertrophy in response to three different pathophysiological stimuli (high\u2010fat diet, isoproterenol, or cold exposure). The heart weight\/tibia length ratio and the cardiomyocyte area (as measures of cardiac hypertrophy development) under hypertrophy\u2010inducing conditions were lower in\n                    <jats:italic>Fgf15<\/jats:italic>\n                    \u2010null mice than in wild\u2010type mice, whereas the levels of the cardiac damage marker atrial natriuretic factor (\n                    <jats:italic>Nppa<\/jats:italic>\n                    ) were up\u2010regulated. Echocardiographic measurements showed similar results. Moreover, the genes involved in fatty acid metabolism were down\u2010regulated in\n                    <jats:italic>Fgf15<\/jats:italic>\n                    \u2010null mice. Conversely, experimental increases in FGF15 induced cardiac hypertrophy\n                    <jats:italic>in vivo<\/jats:italic>\n                    , without changes in\n                    <jats:italic>Nppa<\/jats:italic>\n                    and up\u2010regulation of metabolic genes. Finally,\n                    <jats:italic>in vitro<\/jats:italic>\n                    studies using cardiomyocytes showed that FGF19 had a direct effect on these cells promoting hypertrophy. We have identified herein an inter\u2010organ signaling pathway that runs from the gut to the heart, acts through the enterokine FGF15\/19, and is involved in cardiac hypertrophy development and regulation of fatty acid metabolism in the myocardium. \u00a9 2023 The Authors.\n                    <jats:italic>The Journal of Pathology<\/jats:italic>\n                    published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.6193","type":"journal-article","created":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T04:51:23Z","timestamp":1693457483000},"page":"335-348","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A new\n                    <scp>FGF15<\/scp>\n                    \/19\u2010mediated gut\u2010to\u2010heart axis controls cardiac hypertrophy"],"prefix":"10.1002","volume":"261","author":[{"given":"Samantha","family":"Mor\u00f3n\u2010Ros","sequence":"first","affiliation":[{"name":"Departament de Bioqu\u00edmica i Biomedicina Molecular Institut de Biomedicina (IBUB), Universitat de Barcelona and CIBER Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4686-6075","authenticated-orcid":false,"given":"Albert","family":"Blasco\u2010Roset","sequence":"additional","affiliation":[{"name":"Departament de Bioqu\u00edmica i Biomedicina Molecular Institut de Biomedicina (IBUB), Universitat de Barcelona and CIBER Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artur","family":"Navarro\u2010Gascon","sequence":"additional","affiliation":[{"name":"Departament de Bioqu\u00edmica i Biomedicina Molecular Institut de Biomedicina (IBUB), Universitat de Barcelona and CIBER Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia","family":"Rup\u00e9rez","sequence":"additional","affiliation":[{"name":"Departament de Bioqu\u00edmica i Biomedicina Molecular Institut de Biomedicina (IBUB), Universitat de Barcelona and CIBER Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Zamora","sequence":"additional","affiliation":[{"name":"Fetal i+D Fetal Medicine Research Center, BCNatal \u2013 Barcelona Center for Maternal\u2010Fetal and Neonatal Medicine (Hospital Clinic and Hospital San Juan de Deu) Institut Clinic de Ginecologia, Obstetricia i Neonatalogia, Institut d'Investigacions Biomediques August Pi i Sunyer, University of Barcelona  Barcelona 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