{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T15:31:38Z","timestamp":1783179098312,"version":"3.54.6"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","funder":[{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["67724"],"award-info":[{"award-number":["67724"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["91469"],"award-info":[{"award-number":["91469"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["112330"],"award-info":[{"award-number":["112330"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["138720"],"award-info":[{"award-number":["138720"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["144626"],"award-info":[{"award-number":["144626"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["150881"],"award-info":[{"award-number":["150881"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"HHS | NIH | National Institute on Aging","doi-asserted-by":"publisher","award":["23039"],"award-info":[{"award-number":["23039"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001674","name":"Fondation Leducq","doi-asserted-by":"publisher","award":["15CVD04"],"award-info":[{"award-number":["15CVD04"]}],"id":[{"id":"10.13039\/501100001674","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["20MERIT35120374"],"award-info":[{"award-number":["20MERIT35120374"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2021,6,25]]},"abstract":"<jats:sec>\n            <jats:title>Rationale:<\/jats:title>\n            <jats:p>Diabetic cardiomyopathy is accompanied by increased production of NADH, predominantly through oxidation of fatty acids and consequent increases in oxidative stress. The role of Nampt (nicotinamide phosphoribosyltransferase), the rate-limiting enzyme of the salvage pathway of nicotinamide adenine dinucleotide synthesis, in the development of diabetic cardiomyopathy is poorly understood.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Objective:<\/jats:title>\n            <jats:p>We investigated the role of endogenous and exogenous Nampt during the development of diabetic cardiomyopathy in response to high-fat diet (HFD) consumption and in the context of oxidative stress.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results:<\/jats:title>\n            <jats:p>\n              HFD consumption upregulated endogenous Nampt, and HFD-induced cardiac diastolic dysfunction, fibrosis, apoptosis, and proinflammatory signaling were alleviated in transgenic mice with cardiac-specific overexpression of Nampt. The alleviation of diastolic dysfunction observed in these mice was abolished by inhibition of NADP(H) production via NADK (NAD kinase) inhibition. Nampt overexpression decreased oxidation of GSH (glutathione) and Trx1 (thioredoxin 1) targets, dityrosine, and the accumulation of toxic lipids, including ceramides and diglycerides, in the presence of HFD consumption. Nampt overexpression upregulated not only NAD\n              <jats:sup>+<\/jats:sup>\n              (nicotinamide adenine dinucleotide) but also NADP\n              <jats:sup>+<\/jats:sup>\n              (nicotinamide adenine dinucleotide phosphate) and NADPH in the heart and in cultured cardiomyocytes, which, in turn, stimulated the glutathione and Trx1 systems and alleviated oxidative stress in the heart induced by HFD consumption. In cultured cardiomyocytes, Nampt-induced upregulation of NADPH was abolished in the presence of NADK knockdown, whereas that of NAD\n              <jats:sup>+<\/jats:sup>\n              was not. Nampt overexpression attenuated H\n              <jats:sub>2<\/jats:sub>\n              O\n              <jats:sub>2<\/jats:sub>\n              -induced oxidative inhibition of Prdx1 (peroxiredoxin 1) and mTOR (mammalian target of rapamycin) in an NADK-dependent manner in cultured cardiomyocytes. Nampt overexpression also attenuated H\n              <jats:sub>2<\/jats:sub>\n              O\n              <jats:sub>2<\/jats:sub>\n              -induced cell death, an effect that was partly abolished by inhibition of NADK, Trx1, or glutathione synthesis. In contrast, oxidative stress and the development of diabetic cardiomyopathy in response to HFD consumption were exacerbated in Nampt heterozygous knockout (Nampt\n              <jats:sup>+\/\u2212<\/jats:sup>\n              ) mice.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>\n              Nampt-mediated production of NAD\n              <jats:sup>+<\/jats:sup>\n              protects against oxidative stress, in part, through the NADPH-dependent reducing system, thereby alleviating the development of diabetic cardiomyopathy in response to HFD consumption.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.120.317943","type":"journal-article","created":{"date-parts":[[2021,4,30]],"date-time":"2021-04-30T09:02:02Z","timestamp":1619773322000},"page":"114-130","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":57,"title":["Nampt Potentiates Antioxidant Defense in Diabetic Cardiomyopathy"],"prefix":"10.1161","volume":"129","author":[{"given":"Shin-ichi","family":"Oka","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Molecular Medicine (S.-i.O., J.B., C.-y.H., N.I., G.R., P.Z., X.X., S.K., M.T., Y.I., W.M., T.K., J.S.), Rutgers New Jersey Medical School, Newark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2196-7339","authenticated-orcid":true,"given":"Jaemin","family":"Byun","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Molecular Medicine (S.-i.O., J.B., C.-y.H., N.I., G.R., P.Z., X.X., S.K., M.T., Y.I., W.M., T.K., J.S.), Rutgers New Jersey Medical School, Newark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-yang","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Molecular Medicine (S.-i.O., J.B., C.-y.H., N.I., G.R., P.Z., X.X., S.K., M.T., Y.I., W.M., T.K., J.S.), Rutgers New Jersey Medical School, Newark."},{"name":"Division of Cardiovascular Surgery, Department of Surgery, Taipei Veterans General Hospital, Taiwan (C.-y.H.)."},{"name":"Institute of Clinical Medicine, School of Medicine National Yang-Ming University, Taipei, Taiwan (C.-y.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7985-4150","authenticated-orcid":true,"given":"Nobushige","family":"Imai","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Molecular Medicine (S.-i.O., J.B., C.-y.H., N.I., G.R., P.Z., X.X., S.K., M.T., Y.I., W.M., T.K., J.S.), Rutgers New Jersey Medical School, Newark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guersom","family":"Ralda","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Molecular Medicine (S.-i.O., J.B., C.-y.H., N.I., G.R., P.Z., X.X., S.K., M.T., Y.I., W.M., T.K., J.S.), Rutgers New Jersey Medical School, Newark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiyong","family":"Zhai","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Molecular Medicine (S.-i.O., J.B., C.-y.H., N.I., G.R., P.Z., X.X., S.K., M.T., Y.I., W.M., T.K., J.S.), Rutgers New Jersey Medical School, Newark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyong","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Molecular Medicine (S.-i.O., J.B., C.-y.H., N.I., G.R., P.Z., X.X., S.K., M.T., Y.I., W.M., T.K., J.S.), Rutgers New Jersey Medical School, Newark."},{"name":"Department of Cardiology, Ningbo Medical Center Lihuili Hospital, Zhejiang, China (X.X.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanchita","family":"Kashyap","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Molecular Medicine (S.-i.O., J.B., C.-y.H., N.I., G.R., P.Z., X.X., S.K., M.T., Y.I., W.M., T.K., J.S.), Rutgers New Jersey Medical School, Newark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5231-4181","authenticated-orcid":true,"given":"Junco S.","family":"Warren","sequence":"additional","affiliation":[{"name":"Nora Eccles Harrison Cardiovascular Research and Training Institute (J.S.W.), University of Utah, Salt Lake City."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Alan Maschek","sequence":"additional","affiliation":[{"name":"Metabolomics, Proteomics, and Mass Spectrometry Cores (J.A.M.), University of Utah, Salt Lake City."},{"name":"Department of Nutrition and Integrative Physiology (J.A.M.), University of Utah, Salt Lake City."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trevor S.","family":"Tippetts","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Integrative Physiology and the Diabetes and Metabolism Research Center (T.S.T., S.V.), University of Utah, Salt Lake City."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingming","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Molecular Medicine (S.-i.O., J.B., C.-y.H., N.I., G.R., P.Z., X.X., S.K., M.T., Y.I., W.M., T.K., J.S.), Rutgers New Jersey Medical School, Newark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sundararajan","family":"Venkatesh","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Biochemistry, and Molecular Genetics (S.V.), Rutgers New Jersey Medical School, Newark."},{"name":"Department of Nutrition and Integrative Physiology and the Diabetes and Metabolism Research Center (T.S.T., S.V.), University of Utah, Salt Lake City."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5452-1504","authenticated-orcid":true,"given":"Yoshiyuki","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Molecular Medicine (S.-i.O., J.B., C.-y.H., N.I., G.R., P.Z., X.X., S.K., M.T., Y.I., W.M., T.K., J.S.), Rutgers New Jersey Medical School, Newark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wataru","family":"Mizushima","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Molecular Medicine (S.-i.O., J.B., C.-y.H., N.I., G.R., P.Z., X.X., S.K., M.T., Y.I., W.M., T.K., J.S.), Rutgers New Jersey Medical School, Newark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihide","family":"Kashihara","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Molecular Medicine (S.-i.O., J.B., C.-y.H., N.I., G.R., P.Z., X.X., S.K., M.T., Y.I., W.M., T.K., J.S.), Rutgers New Jersey Medical School, Newark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3724-4132","authenticated-orcid":true,"given":"Junichi","family":"Sadoshima","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Molecular Medicine (S.-i.O., J.B., C.-y.H., N.I., G.R., P.Z., X.X., S.K., M.T., Y.I., W.M., T.K., J.S.), Rutgers New Jersey Medical School, Newark."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-48382-5_1"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hfc.2019.02.003"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2019.08.035"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.306842"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.314607"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.111.247932"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/5028181"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2016.12.020"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2018.03.051"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003544"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau3903"},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.06.044"},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aaq0702"},{"key":"e_1_3_6_15_2","doi-asserted-by":"publisher","DOI":"10.4161\/auto.5.8.10275"},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.203703"},{"key":"e_1_3_6_17_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00222.2019"},{"key":"e_1_3_6_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.01.005"},{"key":"e_1_3_6_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10741-013-9405-8"},{"key":"e_1_3_6_20_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.114.096727"},{"key":"e_1_3_6_21_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.807735"},{"key":"e_1_3_6_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.12.013"},{"key":"e_1_3_6_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2152"},{"key":"e_1_3_6_24_2","doi-asserted-by":"publisher","DOI":"10.1113\/JP276747"},{"key":"e_1_3_6_25_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.7.2005"},{"key":"e_1_3_6_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2007.09.003"},{"key":"e_1_3_6_27_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.302922"},{"key":"e_1_3_6_28_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2017.7415"},{"key":"e_1_3_6_29_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2005.7.1568"},{"key":"e_1_3_6_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11078-z"},{"key":"e_1_3_6_31_2","first-page":"29","article-title":"[The sirtuin family: regulators that connect metabolism, aging, and longevity].","volume":"23","author":"Imai S","year":"2013","unstructured":"Imai, S. [The sirtuin family: regulators that connect metabolism, aging, and longevity]. Clin Calcium. 2013;23:29\u201338. doi: CliCa13012938","journal-title":"Clin Calcium"},{"key":"e_1_3_6_32_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0098972"},{"key":"e_1_3_6_33_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.09-151308"},{"key":"e_1_3_6_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2019.05.019"},{"key":"e_1_3_6_35_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.958033"},{"key":"e_1_3_6_36_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.228437"},{"key":"e_1_3_6_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2011.10.001"},{"key":"e_1_3_6_38_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.D700041-JLR200"},{"key":"e_1_3_6_39_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv380"},{"key":"e_1_3_6_40_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvz251"}],"container-title":["Circulation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCRESAHA.120.317943","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T05:07:11Z","timestamp":1715576831000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCRESAHA.120.317943"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,25]]},"references-count":39,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,6,25]]}},"alternative-id":["10.1161\/CIRCRESAHA.120.317943"],"URL":"https:\/\/doi.org\/10.1161\/circresaha.120.317943","relation":{},"ISSN":["0009-7330","1524-4571"],"issn-type":[{"value":"0009-7330","type":"print"},{"value":"1524-4571","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,25]]},"assertion":[{"value":"2020-08-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-04-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-04-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}