{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:56:14Z","timestamp":1790711774098,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T00:00:00Z","timestamp":1698624000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81970411"],"award-info":[{"award-number":["81970411"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82270359"],"award-info":[{"award-number":["82270359"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81970317"],"award-info":[{"award-number":["81970317"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Diabetic cardiomyopathy, a distinctive complication of diabetes mellitus, has been correlated with the presence of intracellular lipid deposits. However, the intricate molecular mechanisms governing the aberrant accumulation of lipid droplets within cardiomyocytes remain to be comprehensively elucidated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Both obese diabetic (db\/db) mice and HL\u20101 cells treated with 200\u00a0\u03bcmol\/L palmitate and 200\u00a0\u03bcmol\/L oleate were used to simulate type 2 diabetes conditions. Transmission electron microscopy is employed to assess the size and quantity of lipid droplets in the mouse hearts. Transcriptomics analysis was utilized to interrogate mRNA levels. Lipidomics and ubiquitinomics were employed to explore the lipid composition alterations and proteins participating in ubiquitin\u2010mediated degradation in mice. Clinical data were collected from patients with diabetes\u2010associated cardiomyopathy and healthy controls. Western blot analysis was conducted to assess the levels of proteins linked to lipid metabolism, and the biotin\u2010switch assay was employed to quantify protein cysteine S\u2010sulfhydration levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The administration of H\n                      <jats:sub>2<\/jats:sub>\n                      S donor, NaHS, effectively restored hydrogen sulfide levels in both the cardiac tissue and plasma of db\/db mice (+7%,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.001; +5%,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.001). Both db\/db mice (+210%,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.001) and diabetic patients (+83%,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.22,\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a05) exhibit elevated plasma triglyceride levels. Treatment with GYY4137 effectively lowers triglyceride levels in db\/db mice (\u221243%,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.007). The expression of cystathionine gamma\u2010lyase and HMG\u2010CoA reductase degradation protein 1 (SYVN1) was decreased in db\/db mice compared with the wild\u2010type mice (cystathionine gamma\u2010lyase: \u221231%,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0240; SYVN1: \u221235%,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.01), and NaHS\u2010treated mice (SYVN1: \u221231%,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.03). Conversely, the expression of sterol regulatory element\u2010binding protein 1 (SREBP1) was elevated (+91%,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.007; +51%,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.03 compared with control and NaHS\u2010treated mice, respectively), along with diacylglycerol\n                      <jats:italic>O<\/jats:italic>\n                      \u2010acyltransferase 1 (DGAT1) (+95%,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.001; +35%,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.02) and 1\u2010acylglycerol\u20103\u2010phosphate\n                      <jats:italic>O<\/jats:italic>\n                      \u2010acyltransferase 3 (AGPAT3) (+88%,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.01; +22%,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.32). Exogenous H\n                      <jats:sub>2<\/jats:sub>\n                      S led to a reduction in lipid droplet formation (\u221248%,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.001), restoration of SYVN1 expression, modification of SYVN1's S\u2010sulfhydration status and enhancement of SREBP1 ubiquitination. Overexpression of SYVN1 mutated at Cys115 decreased SREBP1 ubiquitination and increased the number of lipid droplets.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Exogenous H\n                      <jats:sub>2<\/jats:sub>\n                      S enhances ubiquitin\u2010proteasome degradation of SREBP1 and reduces its nuclear translocation by modulating SYVN1's cysteine S\u2010sulfhydration. This pathway limits lipid droplet buildup in cardiac myocytes, ameliorating diabetic cardiomyopathy.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.13347","type":"journal-article","created":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T03:46:09Z","timestamp":1698637569000},"page":"2719-2732","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Exogenous H\n                    <sub>2<\/sub>\n                    S promotes ubiquitin\u2010mediated degradation of SREBP1 to alleviate diabetic cardiomyopathy via SYVN1 S\u2010sulfhydration"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3983-4654","authenticated-orcid":false,"given":"Shiwu","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pathophysiology Harbin Medical University  Harbin 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Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kemiao","family":"Pang","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Urologic Surgery First Affiliated Hospital of Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urologic Surgery First Affiliated Hospital of Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanghao","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology Harbin Medical University  Harbin 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of Cachexia, Sarcopenia and Muscle"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.13347","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T00:07:12Z","timestamp":1704931632000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcsm.13347"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,30]]},"references-count":39,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,12]]}},"alternative-id":["10.1002\/jcsm.13347"],"URL":"https:\/\/doi.org\/10.1002\/jcsm.13347","archive":["Portico"],"relation":{},"ISSN":["2190-5991","2190-6009"],"issn-type":[{"value":"2190-5991","type":"print"},{"value":"2190-6009","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,30]]},"assertion":[{"value":"2023-04-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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