DPP-4 inhibitor induces FGF21 expression via sirtuin 1 signaling and improves myocardial energy metabolism
Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used incretin-based therapy for the treatment of type 2 diabetes. We investigated the cardioprotective effect of a DPP-4 inhibitor, vildagliptin ( vilda ), on myocardial metabolism and cardiac performance under pressure overload. Mice were treated...
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| Veröffentlicht in: | Heart and vessels 2021-01, Vol.36 (1), p.136-146 |
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| creator | Furukawa, Nozomi Koitabashi, Norimichi Matsui, Hiroki Sunaga, Hiroaki Umbarawan, Yogi Syamsunarno, Mas Rizky A. A. Yamaguchi, Aiko Obokata, Masaru Hanaoka, Hirofumi Yokoyama, Tomoyuki Kurabayashi, Masahiko |
| description | Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used incretin-based therapy for the treatment of type 2 diabetes. We investigated the cardioprotective effect of a DPP-4 inhibitor, vildagliptin (
vilda
), on myocardial metabolism and cardiac performance under pressure overload. Mice were treated with either vehicle or
vilda
, followed by transverse aortic constriction (TAC). After 3 weeks of TAC, cardiac hypertrophy and impairment of systolic function were attenuated in
vilda
-treated mice. Pressure–volume analysis showed that
vilda
treatment significantly improved left-ventricular contractile efficiency in TAC heart. Myocardial energy substrate analysis showed that
vilda
treatment significantly increased glucose uptake as well as fatty acid uptake. Fibroblast growth factor 21 (FGF21), a peptide involved in the regulation of energy metabolism, increased in TAC heart and was further increased by
vilda
treatment. FGF21 was strongly expressed in cardiac fibroblasts than in cardiomyocytes in mouse heart after TAC with
vilda
treatment.
Vilda
treatment markedly induced FGF21 expression in human cardiac fibroblasts through a sirtuin (Sirt) 1-mediated pathway, suggesting that fibroblast-mediated FGF21 expression may regulate energy metabolism and exert
vilda
-mediated beneficial effects in stressed heart.
Vilda
induced a metabolic regulator, FGF21 expression in cardiac fibroblasts via Sirt1, and increased contractile efficiency in murine pressure-overloaded heart. |
| doi_str_mv | 10.1007/s00380-020-01711-z |
| format | Article |
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vilda
), on myocardial metabolism and cardiac performance under pressure overload. Mice were treated with either vehicle or
vilda
, followed by transverse aortic constriction (TAC). After 3 weeks of TAC, cardiac hypertrophy and impairment of systolic function were attenuated in
vilda
-treated mice. Pressure–volume analysis showed that
vilda
treatment significantly improved left-ventricular contractile efficiency in TAC heart. Myocardial energy substrate analysis showed that
vilda
treatment significantly increased glucose uptake as well as fatty acid uptake. Fibroblast growth factor 21 (FGF21), a peptide involved in the regulation of energy metabolism, increased in TAC heart and was further increased by
vilda
treatment. FGF21 was strongly expressed in cardiac fibroblasts than in cardiomyocytes in mouse heart after TAC with
vilda
treatment.
Vilda
treatment markedly induced FGF21 expression in human cardiac fibroblasts through a sirtuin (Sirt) 1-mediated pathway, suggesting that fibroblast-mediated FGF21 expression may regulate energy metabolism and exert
vilda
-mediated beneficial effects in stressed heart.
Vilda
induced a metabolic regulator, FGF21 expression in cardiac fibroblasts via Sirt1, and increased contractile efficiency in murine pressure-overloaded heart.</description><identifier>ISSN: 0910-8327</identifier><identifier>EISSN: 1615-2573</identifier><identifier>DOI: 10.1007/s00380-020-01711-z</identifier><identifier>PMID: 33073318</identifier><language>eng</language><publisher>Tokyo: Springer Japan</publisher><subject>Aorta ; Biomedical Engineering and Bioengineering ; Cardiac Surgery ; Cardiology ; Cardiomyocytes ; Diabetes mellitus (non-insulin dependent) ; Dipeptidyl-peptidase IV ; Energy metabolism ; Energy resources ; Fatty acids ; Fibroblast growth factors ; Fibroblasts ; Growth factors ; Heart ; Hypertrophy ; Medicine ; Medicine & Public Health ; Metabolism ; Muscle contraction ; Original ; Original Article ; Overloading ; Peptidase ; Peptidases ; Pressure ; SIRT1 protein ; Substrates ; Vascular Surgery ; Ventricle</subject><ispartof>Heart and vessels, 2021-01, Vol.36 (1), p.136-146</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c697t-db490aba3838547ba6d05977ee8e733b78fc7b40f33f3161622cb9c248738443</citedby><cites>FETCH-LOGICAL-c697t-db490aba3838547ba6d05977ee8e733b78fc7b40f33f3161622cb9c248738443</cites><orcidid>0000-0002-2113-3422</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00380-020-01711-z$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00380-020-01711-z$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33073318$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Furukawa, Nozomi</creatorcontrib><creatorcontrib>Koitabashi, Norimichi</creatorcontrib><creatorcontrib>Matsui, Hiroki</creatorcontrib><creatorcontrib>Sunaga, Hiroaki</creatorcontrib><creatorcontrib>Umbarawan, Yogi</creatorcontrib><creatorcontrib>Syamsunarno, Mas Rizky A. A.</creatorcontrib><creatorcontrib>Yamaguchi, Aiko</creatorcontrib><creatorcontrib>Obokata, Masaru</creatorcontrib><creatorcontrib>Hanaoka, Hirofumi</creatorcontrib><creatorcontrib>Yokoyama, Tomoyuki</creatorcontrib><creatorcontrib>Kurabayashi, Masahiko</creatorcontrib><title>DPP-4 inhibitor induces FGF21 expression via sirtuin 1 signaling and improves myocardial energy metabolism</title><title>Heart and vessels</title><addtitle>Heart Vessels</addtitle><addtitle>Heart Vessels</addtitle><description>Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used incretin-based therapy for the treatment of type 2 diabetes. We investigated the cardioprotective effect of a DPP-4 inhibitor, vildagliptin (
vilda
), on myocardial metabolism and cardiac performance under pressure overload. Mice were treated with either vehicle or
vilda
, followed by transverse aortic constriction (TAC). After 3 weeks of TAC, cardiac hypertrophy and impairment of systolic function were attenuated in
vilda
-treated mice. Pressure–volume analysis showed that
vilda
treatment significantly improved left-ventricular contractile efficiency in TAC heart. Myocardial energy substrate analysis showed that
vilda
treatment significantly increased glucose uptake as well as fatty acid uptake. Fibroblast growth factor 21 (FGF21), a peptide involved in the regulation of energy metabolism, increased in TAC heart and was further increased by
vilda
treatment. FGF21 was strongly expressed in cardiac fibroblasts than in cardiomyocytes in mouse heart after TAC with
vilda
treatment.
Vilda
treatment markedly induced FGF21 expression in human cardiac fibroblasts through a sirtuin (Sirt) 1-mediated pathway, suggesting that fibroblast-mediated FGF21 expression may regulate energy metabolism and exert
vilda
-mediated beneficial effects in stressed heart.
Vilda
induced a metabolic regulator, FGF21 expression in cardiac fibroblasts via Sirt1, and increased contractile efficiency in murine pressure-overloaded heart.</description><subject>Aorta</subject><subject>Biomedical Engineering and Bioengineering</subject><subject>Cardiac Surgery</subject><subject>Cardiology</subject><subject>Cardiomyocytes</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Dipeptidyl-peptidase IV</subject><subject>Energy metabolism</subject><subject>Energy resources</subject><subject>Fatty acids</subject><subject>Fibroblast growth factors</subject><subject>Fibroblasts</subject><subject>Growth factors</subject><subject>Heart</subject><subject>Hypertrophy</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolism</subject><subject>Muscle contraction</subject><subject>Original</subject><subject>Original Article</subject><subject>Overloading</subject><subject>Peptidase</subject><subject>Peptidases</subject><subject>Pressure</subject><subject>SIRT1 protein</subject><subject>Substrates</subject><subject>Vascular Surgery</subject><subject>Ventricle</subject><issn>0910-8327</issn><issn>1615-2573</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><recordid>eNp9kU9v3CAQxVHVqtmm_QI9VEi95OIWGGzwpVKVdtNKkZJD7ggwdljZsAV71c2nD9tN0z-HHBAjze89ZngIvaXkAyVEfMyEgCQVYeVQQWl19wytaEPritUCnqMVaSmpJDBxgl7lvCGE1i1tX6ITACIAqFyhzZfr64pjH2698XNMpeoW6zJeX6wZxe7nNrmcfQx45zXOPs2LD5iWagh69GHAOnTYT9sUd0U17aPVqfN6xC64NOzx5GZt4ujz9Bq96PWY3ZuH-xTdrL_enH-rLq8uvp9_vqxs04q56gxviTYaJMiaC6ObjtStEM5JV4Y2QvZWGE56gB7Ktg1j1rSWcSlAcg6n6NPRdruYyXXWhTnpUW2Tn3Taq6i9-rcT_K0a4k4JISXhdTE4ezBI8cfi8qwmn60bRx1cXLJivGakBYAD-v4_dBOXVD7mQIlaCsZ5Uyh2pGyKOSfXPw5DiTokqY5JqpKk-pWkuiuid3-v8Sj5HV0B4Ajk0gqDS3_efsL2Hsjgqjc</recordid><startdate>20210101</startdate><enddate>20210101</enddate><creator>Furukawa, Nozomi</creator><creator>Koitabashi, Norimichi</creator><creator>Matsui, Hiroki</creator><creator>Sunaga, Hiroaki</creator><creator>Umbarawan, Yogi</creator><creator>Syamsunarno, Mas Rizky A. A.</creator><creator>Yamaguchi, Aiko</creator><creator>Obokata, Masaru</creator><creator>Hanaoka, Hirofumi</creator><creator>Yokoyama, Tomoyuki</creator><creator>Kurabayashi, Masahiko</creator><general>Springer Japan</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-2113-3422</orcidid></search><sort><creationdate>20210101</creationdate><title>DPP-4 inhibitor induces FGF21 expression via sirtuin 1 signaling and improves myocardial energy metabolism</title><author>Furukawa, Nozomi ; Koitabashi, Norimichi ; Matsui, Hiroki ; Sunaga, Hiroaki ; Umbarawan, Yogi ; Syamsunarno, Mas Rizky A. 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A.</creatorcontrib><creatorcontrib>Yamaguchi, Aiko</creatorcontrib><creatorcontrib>Obokata, Masaru</creatorcontrib><creatorcontrib>Hanaoka, Hirofumi</creatorcontrib><creatorcontrib>Yokoyama, Tomoyuki</creatorcontrib><creatorcontrib>Kurabayashi, Masahiko</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Heart and vessels</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Furukawa, Nozomi</au><au>Koitabashi, Norimichi</au><au>Matsui, Hiroki</au><au>Sunaga, Hiroaki</au><au>Umbarawan, Yogi</au><au>Syamsunarno, Mas Rizky A. A.</au><au>Yamaguchi, Aiko</au><au>Obokata, Masaru</au><au>Hanaoka, Hirofumi</au><au>Yokoyama, Tomoyuki</au><au>Kurabayashi, Masahiko</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>DPP-4 inhibitor induces FGF21 expression via sirtuin 1 signaling and improves myocardial energy metabolism</atitle><jtitle>Heart and vessels</jtitle><stitle>Heart Vessels</stitle><addtitle>Heart Vessels</addtitle><date>2021-01-01</date><risdate>2021</risdate><volume>36</volume><issue>1</issue><spage>136</spage><epage>146</epage><pages>136-146</pages><issn>0910-8327</issn><eissn>1615-2573</eissn><abstract>Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used incretin-based therapy for the treatment of type 2 diabetes. We investigated the cardioprotective effect of a DPP-4 inhibitor, vildagliptin (
vilda
), on myocardial metabolism and cardiac performance under pressure overload. Mice were treated with either vehicle or
vilda
, followed by transverse aortic constriction (TAC). After 3 weeks of TAC, cardiac hypertrophy and impairment of systolic function were attenuated in
vilda
-treated mice. Pressure–volume analysis showed that
vilda
treatment significantly improved left-ventricular contractile efficiency in TAC heart. Myocardial energy substrate analysis showed that
vilda
treatment significantly increased glucose uptake as well as fatty acid uptake. Fibroblast growth factor 21 (FGF21), a peptide involved in the regulation of energy metabolism, increased in TAC heart and was further increased by
vilda
treatment. FGF21 was strongly expressed in cardiac fibroblasts than in cardiomyocytes in mouse heart after TAC with
vilda
treatment.
Vilda
treatment markedly induced FGF21 expression in human cardiac fibroblasts through a sirtuin (Sirt) 1-mediated pathway, suggesting that fibroblast-mediated FGF21 expression may regulate energy metabolism and exert
vilda
-mediated beneficial effects in stressed heart.
Vilda
induced a metabolic regulator, FGF21 expression in cardiac fibroblasts via Sirt1, and increased contractile efficiency in murine pressure-overloaded heart.</abstract><cop>Tokyo</cop><pub>Springer Japan</pub><pmid>33073318</pmid><doi>10.1007/s00380-020-01711-z</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-2113-3422</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Springer Nature - Complete Springer Journals |
| subjects | Aorta Biomedical Engineering and Bioengineering Cardiac Surgery Cardiology Cardiomyocytes Diabetes mellitus (non-insulin dependent) Dipeptidyl-peptidase IV Energy metabolism Energy resources Fatty acids Fibroblast growth factors Fibroblasts Growth factors Heart Hypertrophy Medicine Medicine & Public Health Metabolism Muscle contraction Original Original Article Overloading Peptidase Peptidases Pressure SIRT1 protein Substrates Vascular Surgery Ventricle |
| title | DPP-4 inhibitor induces FGF21 expression via sirtuin 1 signaling and improves myocardial energy metabolism |
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