Apelin regulates FoxO3 translocation to mediate cardioprotective responses to myocardial injury and obesity
The increasing incidence of obesity accentuates the importance of identifying mechanisms and optimal therapeutic strategies for patients with heart failure (HF) in relation to obesity status. Here, we investigated the association between plasma level of apelin, an adipocyte-derived factor and clinic...
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| Veröffentlicht in: | Scientific reports 2015-11, Vol.5 (1), p.16104-16104, Article 16104 |
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| creator | Boal, Frederic Roumegoux, Jessica Alfarano, Chiara Timotin, Andrei Calise, Denis Anesia, Rodica Drougard, Anne Knauf, Claude Lagente, Christine Roncalli, Jerome Desmoulin, Franck Tronchere, Helene Valet, Philippe Parini, Angelo Kunduzova, Oksana |
| description | The increasing incidence of obesity accentuates the importance of identifying mechanisms and optimal therapeutic strategies for patients with heart failure (HF) in relation to obesity status. Here, we investigated the association between plasma level of apelin, an adipocyte-derived factor and clinicopathological features of obese and non-obese patients with HF. We further explored potential regulatory mechanisms of cardiac cell fate responses in conditions combining myocardial injury and obesity. In a prospective, cross-sectional study involving patients with HF we show that obese patients (BMI ≥30 kg/m
2
) have higher left ventricular ejection fraction (LVEF) and greater levels of plasma apelin (p |
| doi_str_mv | 10.1038/srep16104 |
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2
) have higher left ventricular ejection fraction (LVEF) and greater levels of plasma apelin (p < 0.005) than non-obese patients (< 30 kg/m
2
), independently of ischemic etiology. In a mouse model combining ischemia-reperfusion (I/R) injury and high-fat diet (HFD)-induced obesity, we identify apelin as a novel regulator of FoxO3 trafficking in cardiomyocytes. Confocal microscopy analysis of cardiac cells revealed that apelin prevents nuclear translocation of FoxO3 in response to oxygen deprivation through a PI3K pathway. These findings uncover apelin as a novel regulator of FoxO3 nucleocytoplasmic trafficking in cardiac cells in response to stress and provide insight into its potential clinical relevance in obese patients with HF.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep16104</identifier><identifier>PMID: 26542760</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>1-Phosphatidylinositol 3-kinase ; 14 ; 14/19 ; 14/28 ; 38 ; 38/77 ; 59 ; 631/443/592/75 ; 64 ; 64/60 ; 692/699/75/230 ; 82 ; Adipocytes - metabolism ; Aged ; Animals ; Beta blockers ; Cardiomyocytes ; Cardiotonic Agents - metabolism ; Cell fate ; Cells, Cultured ; Confocal microscopy ; Cross-Sectional Studies ; Diet, High-Fat - adverse effects ; Disease Models, Animal ; Etiology ; Female ; Forkhead Transcription Factors - metabolism ; FOXO3 protein ; Heart diseases ; Heart Failure ; High fat diet ; Humanities and Social Sciences ; Humans ; Intercellular Signaling Peptides and Proteins - blood ; Intercellular Signaling Peptides and Proteins - metabolism ; Ischemia ; Male ; Mice ; Mice, Inbred C57BL ; Middle Aged ; multidisciplinary ; Myocardial Reperfusion Injury - metabolism ; Myocardium - metabolism ; Myocytes, Cardiac - metabolism ; Nuclear transport ; Obesity ; Obesity - metabolism ; Phosphatidylinositol 3-Kinases - metabolism ; Prospective Studies ; Rats ; Reperfusion ; Rodents ; Science ; Translocation ; Ventricle ; Ventricular Function, Left - physiology</subject><ispartof>Scientific reports, 2015-11, Vol.5 (1), p.16104-16104, Article 16104</ispartof><rights>The Author(s) 2015</rights><rights>Copyright Nature Publishing Group Nov 2015</rights><rights>Copyright © 2015, Macmillan Publishers Limited 2015 Macmillan Publishers Limited</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c504t-5bfff1f38dcd883086103a7121c58659e6587f4e489a70217548a63821675e163</citedby><cites>FETCH-LOGICAL-c504t-5bfff1f38dcd883086103a7121c58659e6587f4e489a70217548a63821675e163</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4635427/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4635427/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,41120,42189,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26542760$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Boal, Frederic</creatorcontrib><creatorcontrib>Roumegoux, Jessica</creatorcontrib><creatorcontrib>Alfarano, Chiara</creatorcontrib><creatorcontrib>Timotin, Andrei</creatorcontrib><creatorcontrib>Calise, Denis</creatorcontrib><creatorcontrib>Anesia, Rodica</creatorcontrib><creatorcontrib>Drougard, Anne</creatorcontrib><creatorcontrib>Knauf, Claude</creatorcontrib><creatorcontrib>Lagente, Christine</creatorcontrib><creatorcontrib>Roncalli, Jerome</creatorcontrib><creatorcontrib>Desmoulin, Franck</creatorcontrib><creatorcontrib>Tronchere, Helene</creatorcontrib><creatorcontrib>Valet, Philippe</creatorcontrib><creatorcontrib>Parini, Angelo</creatorcontrib><creatorcontrib>Kunduzova, Oksana</creatorcontrib><title>Apelin regulates FoxO3 translocation to mediate cardioprotective responses to myocardial injury and obesity</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>The increasing incidence of obesity accentuates the importance of identifying mechanisms and optimal therapeutic strategies for patients with heart failure (HF) in relation to obesity status. Here, we investigated the association between plasma level of apelin, an adipocyte-derived factor and clinicopathological features of obese and non-obese patients with HF. We further explored potential regulatory mechanisms of cardiac cell fate responses in conditions combining myocardial injury and obesity. In a prospective, cross-sectional study involving patients with HF we show that obese patients (BMI ≥30 kg/m
2
) have higher left ventricular ejection fraction (LVEF) and greater levels of plasma apelin (p < 0.005) than non-obese patients (< 30 kg/m
2
), independently of ischemic etiology. In a mouse model combining ischemia-reperfusion (I/R) injury and high-fat diet (HFD)-induced obesity, we identify apelin as a novel regulator of FoxO3 trafficking in cardiomyocytes. Confocal microscopy analysis of cardiac cells revealed that apelin prevents nuclear translocation of FoxO3 in response to oxygen deprivation through a PI3K pathway. These findings uncover apelin as a novel regulator of FoxO3 nucleocytoplasmic trafficking in cardiac cells in response to stress and provide insight into its potential clinical relevance in obese patients with HF.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>14</subject><subject>14/19</subject><subject>14/28</subject><subject>38</subject><subject>38/77</subject><subject>59</subject><subject>631/443/592/75</subject><subject>64</subject><subject>64/60</subject><subject>692/699/75/230</subject><subject>82</subject><subject>Adipocytes - metabolism</subject><subject>Aged</subject><subject>Animals</subject><subject>Beta blockers</subject><subject>Cardiomyocytes</subject><subject>Cardiotonic Agents - metabolism</subject><subject>Cell fate</subject><subject>Cells, Cultured</subject><subject>Confocal microscopy</subject><subject>Cross-Sectional Studies</subject><subject>Diet, High-Fat - adverse effects</subject><subject>Disease Models, Animal</subject><subject>Etiology</subject><subject>Female</subject><subject>Forkhead Transcription Factors - metabolism</subject><subject>FOXO3 protein</subject><subject>Heart diseases</subject><subject>Heart Failure</subject><subject>High fat diet</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Intercellular Signaling Peptides and Proteins - blood</subject><subject>Intercellular Signaling Peptides and Proteins - metabolism</subject><subject>Ischemia</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Middle Aged</subject><subject>multidisciplinary</subject><subject>Myocardial Reperfusion Injury - metabolism</subject><subject>Myocardium - metabolism</subject><subject>Myocytes, Cardiac - metabolism</subject><subject>Nuclear transport</subject><subject>Obesity</subject><subject>Obesity - metabolism</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Prospective Studies</subject><subject>Rats</subject><subject>Reperfusion</subject><subject>Rodents</subject><subject>Science</subject><subject>Translocation</subject><subject>Ventricle</subject><subject>Ventricular Function, Left - 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metabolism</topic><topic>Aged</topic><topic>Animals</topic><topic>Beta blockers</topic><topic>Cardiomyocytes</topic><topic>Cardiotonic Agents - metabolism</topic><topic>Cell fate</topic><topic>Cells, Cultured</topic><topic>Confocal microscopy</topic><topic>Cross-Sectional Studies</topic><topic>Diet, High-Fat - adverse effects</topic><topic>Disease Models, Animal</topic><topic>Etiology</topic><topic>Female</topic><topic>Forkhead Transcription Factors - metabolism</topic><topic>FOXO3 protein</topic><topic>Heart diseases</topic><topic>Heart Failure</topic><topic>High fat diet</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Intercellular Signaling Peptides and Proteins - blood</topic><topic>Intercellular Signaling Peptides and Proteins - metabolism</topic><topic>Ischemia</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Middle Aged</topic><topic>multidisciplinary</topic><topic>Myocardial Reperfusion Injury - metabolism</topic><topic>Myocardium - metabolism</topic><topic>Myocytes, Cardiac - metabolism</topic><topic>Nuclear transport</topic><topic>Obesity</topic><topic>Obesity - metabolism</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>Prospective Studies</topic><topic>Rats</topic><topic>Reperfusion</topic><topic>Rodents</topic><topic>Science</topic><topic>Translocation</topic><topic>Ventricle</topic><topic>Ventricular Function, Left - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Boal, Frederic</creatorcontrib><creatorcontrib>Roumegoux, Jessica</creatorcontrib><creatorcontrib>Alfarano, Chiara</creatorcontrib><creatorcontrib>Timotin, Andrei</creatorcontrib><creatorcontrib>Calise, Denis</creatorcontrib><creatorcontrib>Anesia, Rodica</creatorcontrib><creatorcontrib>Drougard, Anne</creatorcontrib><creatorcontrib>Knauf, Claude</creatorcontrib><creatorcontrib>Lagente, Christine</creatorcontrib><creatorcontrib>Roncalli, Jerome</creatorcontrib><creatorcontrib>Desmoulin, Franck</creatorcontrib><creatorcontrib>Tronchere, Helene</creatorcontrib><creatorcontrib>Valet, Philippe</creatorcontrib><creatorcontrib>Parini, Angelo</creatorcontrib><creatorcontrib>Kunduzova, Oksana</creatorcontrib><collection>Springer Nature OA/Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Boal, Frederic</au><au>Roumegoux, Jessica</au><au>Alfarano, Chiara</au><au>Timotin, Andrei</au><au>Calise, Denis</au><au>Anesia, Rodica</au><au>Drougard, Anne</au><au>Knauf, Claude</au><au>Lagente, Christine</au><au>Roncalli, Jerome</au><au>Desmoulin, Franck</au><au>Tronchere, Helene</au><au>Valet, Philippe</au><au>Parini, Angelo</au><au>Kunduzova, Oksana</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Apelin regulates FoxO3 translocation to mediate cardioprotective responses to myocardial injury and obesity</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2015-11-06</date><risdate>2015</risdate><volume>5</volume><issue>1</issue><spage>16104</spage><epage>16104</epage><pages>16104-16104</pages><artnum>16104</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>The increasing incidence of obesity accentuates the importance of identifying mechanisms and optimal therapeutic strategies for patients with heart failure (HF) in relation to obesity status. Here, we investigated the association between plasma level of apelin, an adipocyte-derived factor and clinicopathological features of obese and non-obese patients with HF. We further explored potential regulatory mechanisms of cardiac cell fate responses in conditions combining myocardial injury and obesity. In a prospective, cross-sectional study involving patients with HF we show that obese patients (BMI ≥30 kg/m
2
) have higher left ventricular ejection fraction (LVEF) and greater levels of plasma apelin (p < 0.005) than non-obese patients (< 30 kg/m
2
), independently of ischemic etiology. In a mouse model combining ischemia-reperfusion (I/R) injury and high-fat diet (HFD)-induced obesity, we identify apelin as a novel regulator of FoxO3 trafficking in cardiomyocytes. Confocal microscopy analysis of cardiac cells revealed that apelin prevents nuclear translocation of FoxO3 in response to oxygen deprivation through a PI3K pathway. These findings uncover apelin as a novel regulator of FoxO3 nucleocytoplasmic trafficking in cardiac cells in response to stress and provide insight into its potential clinical relevance in obese patients with HF.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>26542760</pmid><doi>10.1038/srep16104</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 1-Phosphatidylinositol 3-kinase 14 14/19 14/28 38 38/77 59 631/443/592/75 64 64/60 692/699/75/230 82 Adipocytes - metabolism Aged Animals Beta blockers Cardiomyocytes Cardiotonic Agents - metabolism Cell fate Cells, Cultured Confocal microscopy Cross-Sectional Studies Diet, High-Fat - adverse effects Disease Models, Animal Etiology Female Forkhead Transcription Factors - metabolism FOXO3 protein Heart diseases Heart Failure High fat diet Humanities and Social Sciences Humans Intercellular Signaling Peptides and Proteins - blood Intercellular Signaling Peptides and Proteins - metabolism Ischemia Male Mice Mice, Inbred C57BL Middle Aged multidisciplinary Myocardial Reperfusion Injury - metabolism Myocardium - metabolism Myocytes, Cardiac - metabolism Nuclear transport Obesity Obesity - metabolism Phosphatidylinositol 3-Kinases - metabolism Prospective Studies Rats Reperfusion Rodents Science Translocation Ventricle Ventricular Function, Left - physiology |
| title | Apelin regulates FoxO3 translocation to mediate cardioprotective responses to myocardial injury and obesity |
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