{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T03:54:21Z","timestamp":1791431661992,"version":"4.3.3"},"reference-count":53,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2025,4,25]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>Individuals with diabetes are susceptible to cardiac dysfunction and heart failure, potentially resulting in mortality. Metabolic disorders frequently occur in patients with diabetes, and diabetes usually leads to remodeling of heart structure and cardiac dysfunction. However, the contribution and underlying mechanisms of metabolic and structural coupling in diabetic cardiac dysfunction remain elusive.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>Two mouse models of type 2 diabetes (T2DM) were used to assess alterations in glucose\/lipid metabolism and cardiac structure. The potential metabolic-structural coupling molecule ACBP (acyl\u2013coenzyme A\u2013binding protein) was screened from 4 published datasets of T2DM-associated heart disease. In vivo loss-of-function and gain-of-function approaches were used to investigate the role of ACBP in diabetic cardiac dysfunction. The underlying mechanisms of metabolic and structural coupling were investigated by stable-isotope tracing metabolomics, coimmunoprecipitation coupled with mass spectrometry, and chromatin immunoprecipitation sequencing.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              Diabetic mouse hearts exhibit enhanced lipid metabolism and impaired ultrastructure with marked cardiac systolic and diastolic dysfunction. Analysis of 4 T2DM public datasets revealed that\n              <jats:italic>Acbp<\/jats:italic>\n              was a significant lipid metabolism gene whose expression was upregulated. Consistently, ACBP expression levels were markedly elevated in the hearts of patients with diabetes and diabetic mice. Moreover, we constructed cardiomyocyte-specific\n              <jats:italic>Acbp<\/jats:italic>\n              knockout mice that exhibited attenuation of T2DM-induced cardiac remodeling and cardiac dysfunction, including attenuation of cardiac hypertrophy, fibrosis, ultrastructural damage, and enhanced cardiomyocyte contractility and cardiac function. Conversely, cardiac-specific\n              <jats:italic>Acbp<\/jats:italic>\n              overexpression via adeno-associated virus type 9, which encodes\n              <jats:italic>Acbp<\/jats:italic>\n              under the cTnT (cardiac troponin T) promoter, recapitulated cardiac dysfunction. Mechanistically, cardiac-specific\n              <jats:italic>Acbp<\/jats:italic>\n              knockout enhances glucose utilization in diabetic cardiomyocytes, suggesting a potential compensatory mechanism for insufficient ATP levels, highlighting its metabolic role. In addition, combined with mass spectrometry analysis revealed that ACBP binds MyBPC3 (myosin-binding protein C3) in T2DM individuals, which potentially prevents MyBPC3 from assisting the formation of cross-bridge structures between myosin and actin, thereby impairing myocardial contraction. Importantly, chromatin immunoprecipitation sequencing revealed that peroxisome proliferator\u2013activated receptor \u03b3 regulates the transcriptional activity of\n              <jats:italic>Acbp<\/jats:italic>\n              .\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>Our findings demonstrated that ACBP mediates the bidirectional regulation of cardiomyocyte metabolic and structural associations and identified a promising therapeutic target for ameliorating cardiac dysfunction in patients with T2DM.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.124.326044","type":"journal-article","created":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T09:07:40Z","timestamp":1744016860000},"page":"946-967","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":27,"title":["Metabolic Coordination Structures Contribute to Diabetic Myocardial Dysfunction"],"prefix":"10.1161","volume":"136","author":[{"given":"Teng","family":"Wu","sequence":"first","affiliation":[{"name":"Guangdong Engineering &amp; Technology Research Center for Disease-Model Animals, Laboratory Animal Center (T.W., T.H., H.R., C.S., J.Q., X.F., J.W., S.X., Y.J., M.L., H.Z., Y.Z., K.L., Maoquan Yang, Z.S., X. Li, Y.W., Ming Yang, H.L., X.H., J.T., W.C.), Sun Yat-sen University, Guangzhou, China."},{"name":"Department of Biochemistry, Zhongshan School of Medicine (T.W., T.H., H.R., C.S., J.W., S.X., Y.J., M.L., H.Z., K.L., Maoquan Yang, Z.S., X. Li, Y.W., Ming Yang, J.T., W.C.), Sun Yat-sen University, Guangzhou, China."},{"name":"Reproductive Medicine Center, Sun Yat-sen Memorial Hospital (T.W., T.L., W.L., P.L., H.C.), Sun Yat-sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7944-5242","authenticated-orcid":true,"given":"Tongsheng","family":"Huang","sequence":"additional","affiliation":[{"name":"Guangdong Engineering &amp; Technology Research Center for Disease-Model Animals, Laboratory Animal Center (T.W., T.H., H.R., C.S., J.Q., X.F., J.W., S.X., Y.J., M.L., H.Z., Y.Z., K.L., Maoquan Yang, Z.S., X. Li, Y.W., Ming Yang, H.L., X.H., J.T., W.C.), Sun Yat-sen University, Guangzhou, China."},{"name":"Department of Biochemistry, Zhongshan School of Medicine (T.W., T.H., H.R., C.S., J.W., S.X., Y.J., M.L., H.Z., K.L., Maoquan Yang, Z.S., X. Li, Y.W., Ming Yang, J.T., W.C.), Sun Yat-sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6024-7325","authenticated-orcid":true,"given":"Honglin","family":"Ren","sequence":"additional","affiliation":[{"name":"Guangdong Engineering &amp; Technology Research Center for Disease-Model Animals, Laboratory Animal Center (T.W., T.H., H.R., C.S., J.Q., X.F., J.W., S.X., Y.J., M.L., H.Z., Y.Z., K.L., Maoquan Yang, Z.S., X. Li, Y.W., Ming Yang, H.L., X.H., J.T., W.C.), Sun Yat-sen University, Guangzhou, China."},{"name":"Department of Biochemistry, Zhongshan School of Medicine (T.W., T.H., H.R., C.S., J.W., S.X., Y.J., M.L., H.Z., K.L., Maoquan Yang, Z.S., X. Li, Y.W., Ming Yang, J.T., W.C.), Sun Yat-sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conghui","family":"Shen","sequence":"additional","affiliation":[{"name":"Guangdong Engineering &amp; Technology Research Center for Disease-Model Animals, Laboratory Animal Center (T.W., T.H., H.R., C.S., J.Q., X.F., J.W., S.X., Y.J., M.L., H.Z., Y.Z., K.L., Maoquan Yang, Z.S., X. Li, Y.W., Ming Yang, H.L., X.H., J.T., W.C.), Sun Yat-sen University, Guangzhou, China."},{"name":"Department of Biochemistry, Zhongshan School of Medicine (T.W., T.H., H.R., C.S., J.W., S.X., Y.J., M.L., H.Z., K.L., Maoquan Yang, Z.S., X. Li, Y.W., Ming Yang, J.T., W.C.), Sun Yat-sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang","family":"Qian","sequence":"additional","affiliation":[{"name":"Guangdong Engineering &amp; Technology Research Center for Disease-Model Animals, Laboratory Animal Center (T.W., T.H., H.R., C.S., J.Q., X.F., J.W., S.X., Y.J., M.L., H.Z., Y.Z., K.L., Maoquan Yang, Z.S., X. Li, Y.W., Ming Yang, H.L., X.H., J.T., W.C.), Sun Yat-sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinlu","family":"Fu","sequence":"additional","affiliation":[{"name":"Guangdong Engineering &amp; Technology Research Center for Disease-Model Animals, Laboratory Animal Center (T.W., T.H., H.R., C.S., J.Q., X.F., J.W., S.X., Y.J., M.L., H.Z., Y.Z., K.L., Maoquan Yang, Z.S., X. Li, Y.W., Ming Yang, H.L., X.H., J.T., W.C.), Sun Yat-sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shangyuan","family":"Liu","sequence":"additional","affiliation":[{"name":"GMU-GIBH Joint School of Life Sciences, The Guangdong-Hong Kong-Macau Joint Laboratory for Cell Fate Regulation and Diseases, Guangzhou Medical University, China (S.L., C.X.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2706-5379","authenticated-orcid":true,"given":"Chengshu","family":"Xie","sequence":"additional","affiliation":[{"name":"GMU-GIBH Joint School of Life Sciences, The Guangdong-Hong Kong-Macau Joint Laboratory for Cell Fate Regulation and Diseases, Guangzhou Medical University, China (S.L., C.X.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Lin","sequence":"additional","affiliation":[{"name":"ZEISS Microscopy Customer Center China, Shanghai (X. Lin)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhong","family":"Wan","sequence":"additional","affiliation":[{"name":"Guangdong Engineering &amp; Technology Research Center for Disease-Model Animals, Laboratory Animal Center (T.W., T.H., H.R., C.S., J.Q., X.F., J.W., S.X., Y.J., M.L., H.Z., Y.Z., K.L., Maoquan Yang, Z.S., X. Li, Y.W., Ming Yang, H.L., X.H., J.T., W.C.), Sun Yat-sen University, Guangzhou, China."},{"name":"Department of Biochemistry, Zhongshan School of Medicine (T.W., T.H., H.R., C.S., J.W., S.X., Y.J., M.L., H.Z., K.L., Maoquan Yang, Z.S., X. Li, Y.W., Ming Yang, J.T., W.C.), Sun Yat-sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2505-6847","authenticated-orcid":true,"given":"Shijie","family":"Xiong","sequence":"additional","affiliation":[{"name":"Guangdong Engineering &amp; Technology Research Center for Disease-Model Animals, Laboratory Animal Center (T.W., T.H., H.R., C.S., J.Q., X.F., J.W., S.X., Y.J., M.L., H.Z., Y.Z., K.L., Maoquan Yang, Z.S., X. Li, Y.W., Ming Yang, H.L., X.H., J.T., W.C.), Sun Yat-sen University, Guangzhou, China."},{"name":"Department of Biochemistry, Zhongshan School of Medicine (T.W., T.H., H.R., C.S., J.W., S.X., Y.J., M.L., H.Z., K.L., Maoquan Yang, Z.S., X. Li, Y.W., Ming Yang, J.T., W.C.), Sun Yat-sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3171-253X","authenticated-orcid":true,"given":"Yuanjun","family":"Ji","sequence":"additional","affiliation":[{"name":"Guangdong Engineering &amp; Technology Research Center for Disease-Model Animals, Laboratory Animal Center (T.W., T.H., H.R., C.S., J.Q., X.F., J.W., S.X., Y.J., M.L., H.Z., Y.Z., K.L., Maoquan Yang, Z.S., X. Li, Y.W., Ming Yang, H.L., X.H., J.T., W.C.), Sun Yat-sen University, Guangzhou, China."},{"name":"Department of Biochemistry, Zhongshan School of Medicine (T.W., T.H., H.R., C.S., J.W., S.X., Y.J., M.L., H.Z., K.L., Maoquan Yang, Z.S., X. Li, Y.W., Ming Yang, J.T., W.C.), Sun Yat-sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengying","family":"Liu","sequence":"additional","affiliation":[{"name":"Guangdong Engineering &amp; Technology Research Center for Disease-Model Animals, Laboratory Animal Center (T.W., T.H., H.R., C.S., J.Q., X.F., J.W., S.X., Y.J., M.L., H.Z., Y.Z., K.L., Maoquan Yang, Z.S., X. Li, Y.W., Ming Yang, H.L., X.H., J.T., W.C.), Sun Yat-sen University, Guangzhou, China."},{"name":"Department of Biochemistry, Zhongshan School of Medicine (T.W., T.H., H.R., C.S., J.W., S.X., Y.J., M.L., H.Z., K.L., Maoquan Yang, Z.S., X. Li, Y.W., Ming Yang, J.T., W.C.), Sun Yat-sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1904-6853","authenticated-orcid":true,"given":"Huiting","family":"Zheng","sequence":"additional","affiliation":[{"name":"Guangdong Engineering &amp; Technology Research Center for Disease-Model Animals, Laboratory Animal Center (T.W., T.H., H.R., C.S., J.Q., X.F., J.W., S.X., Y.J., M.L., H.Z., Y.Z., K.L., Maoquan Yang, Z.S., X. Li, Y.W., Ming Yang, H.L., X.H., J.T., W.C.), Sun Yat-sen University, Guangzhou, China."},{"name":"Department of Biochemistry, Zhongshan School of Medicine (T.W., T.H., H.R., C.S., J.W., S.X., Y.J., M.L., H.Z., K.L., Maoquan Yang, Z.S., X. Li, Y.W., Ming Yang, J.T., W.C.), Sun Yat-sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4418-1996","authenticated-orcid":true,"given":"Ting","family":"Liang","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Sun Yat-sen Memorial Hospital (T.W., T.L., W.L., P.L., H.C.), Sun Yat-sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8234-950X","authenticated-orcid":true,"given":"Wenyi","family":"Liu","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Sun Yat-sen Memorial Hospital (T.W., T.L., W.L., P.L., H.C.), Sun Yat-sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1719-9197","authenticated-orcid":true,"given":"Yan","family":"Zou","sequence":"additional","affiliation":[{"name":"Guangdong Engineering &amp; Technology Research Center for Disease-Model Animals, Laboratory Animal Center (T.W., T.H., H.R., C.S., J.Q., X.F., J.W., S.X., Y.J., M.L., H.Z., Y.Z., K.L., Maoquan Yang, Z.S., X. Li, Y.W., Ming Yang, H.L., X.H., J.T., W.C.), Sun Yat-sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kingwai","family":"Lai","sequence":"additional","affiliation":[{"name":"Guangdong Engineering &amp; Technology Research Center for Disease-Model Animals, Laboratory Animal Center (T.W., T.H., H.R., C.S., J.Q., X.F., J.W., S.X., Y.J., M.L., H.Z., Y.Z., K.L., Maoquan Yang, Z.S., X. Li, Y.W., Ming Yang, H.L., X.H., J.T., W.C.), Sun Yat-sen University, Guangzhou, China."},{"name":"Department of Biochemistry, Zhongshan School of Medicine (T.W., T.H., H.R., C.S., J.W., S.X., Y.J., M.L., H.Z., K.L., Maoquan Yang, Z.S., X. Li, Y.W., Ming Yang, J.T., W.C.), Sun Yat-sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6542-3260","authenticated-orcid":true,"given":"Maoquan","family":"Yang","sequence":"additional","affiliation":[{"name":"Guangdong Engineering &amp; Technology Research Center for Disease-Model Animals, Laboratory Animal Center (T.W., T.H., H.R., C.S., J.Q., X.F., J.W., S.X., Y.J., M.L., H.Z., Y.Z., K.L., Maoquan Yang, Z.S., X. Li, Y.W., Ming Yang, H.L., X.H., J.T., W.C.), Sun Yat-sen University, Guangzhou, China."},{"name":"Department of Biochemistry, Zhongshan School of Medicine (T.W., T.H., H.R., C.S., J.W., S.X., Y.J., M.L., H.Z., K.L., Maoquan Yang, Z.S., X. Li, Y.W., Ming Yang, J.T., W.C.), Sun Yat-sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyi","family":"Song","sequence":"additional","affiliation":[{"name":"Guangdong Engineering &amp; Technology Research Center for Disease-Model Animals, Laboratory Animal Center (T.W., T.H., H.R., C.S., J.Q., X.F., J.W., S.X., Y.J., M.L., H.Z., Y.Z., K.L., Maoquan Yang, Z.S., X. Li, Y.W., Ming Yang, H.L., X.H., J.T., W.C.), Sun Yat-sen University, Guangzhou, China."},{"name":"Department of Biochemistry, Zhongshan School of Medicine (T.W., T.H., H.R., C.S., J.W., S.X., Y.J., M.L., H.Z., K.L., Maoquan Yang, Z.S., X. Li, Y.W., Ming Yang, J.T., W.C.), Sun Yat-sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peixuan","family":"Lan","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Sun Yat-sen Memorial Hospital (T.W., T.L., W.L., P.L., H.C.), Sun Yat-sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinghui","family":"Li","sequence":"additional","affiliation":[{"name":"Guangdong Engineering &amp; Technology Research Center for Disease-Model Animals, Laboratory Animal Center (T.W., T.H., H.R., C.S., J.Q., X.F., J.W., S.X., Y.J., M.L., H.Z., Y.Z., K.L., Maoquan Yang, Z.S., X. Li, Y.W., Ming Yang, H.L., X.H., J.T., W.C.), Sun Yat-sen University, Guangzhou, China."},{"name":"Department of Biochemistry, Zhongshan School of Medicine (T.W., T.H., H.R., C.S., J.W., S.X., Y.J., M.L., H.Z., K.L., Maoquan Yang, Z.S., X. Li, Y.W., Ming Yang, J.T., W.C.), Sun Yat-sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9380-4109","authenticated-orcid":true,"given":"Yandi","family":"Wu","sequence":"additional","affiliation":[{"name":"Guangdong Engineering &amp; Technology Research Center for Disease-Model Animals, Laboratory Animal Center (T.W., T.H., H.R., C.S., J.Q., X.F., J.W., S.X., Y.J., M.L., H.Z., Y.Z., K.L., Maoquan Yang, Z.S., X. Li, Y.W., Ming Yang, H.L., X.H., J.T., W.C.), Sun Yat-sen University, Guangzhou, China."},{"name":"Department of Biochemistry, Zhongshan School of Medicine (T.W., T.H., H.R., C.S., J.W., S.X., Y.J., M.L., H.Z., K.L., Maoquan Yang, Z.S., X. Li, Y.W., Ming Yang, J.T., W.C.), Sun Yat-sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Yang","sequence":"additional","affiliation":[{"name":"Guangdong Engineering &amp; Technology Research Center for Disease-Model Animals, Laboratory Animal Center (T.W., T.H., H.R., C.S., J.Q., X.F., J.W., S.X., Y.J., M.L., H.Z., Y.Z., K.L., Maoquan Yang, Z.S., X. Li, Y.W., Ming Yang, H.L., X.H., J.T., W.C.), Sun Yat-sen University, Guangzhou, China."},{"name":"Department of Biochemistry, Zhongshan School of Medicine (T.W., T.H., H.R., C.S., J.W., S.X., Y.J., M.L., H.Z., K.L., Maoquan Yang, Z.S., X. Li, Y.W., Ming Yang, J.T., W.C.), Sun Yat-sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Li","sequence":"additional","affiliation":[{"name":"Guangdong Engineering &amp; Technology Research Center for Disease-Model Animals, Laboratory Animal Center (T.W., T.H., H.R., C.S., J.Q., X.F., J.W., S.X., Y.J., M.L., H.Z., Y.Z., K.L., Maoquan Yang, Z.S., X. Li, Y.W., Ming Yang, H.L., X.H., J.T., W.C.), Sun Yat-sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuezhe","family":"Huang","sequence":"additional","affiliation":[{"name":"Guangdong Engineering &amp; Technology Research Center for Disease-Model Animals, Laboratory Animal Center (T.W., T.H., H.R., C.S., J.Q., X.F., J.W., S.X., Y.J., M.L., H.Z., Y.Z., K.L., Maoquan Yang, Z.S., X. Li, Y.W., Ming Yang, H.L., X.H., J.T., W.C.), Sun Yat-sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3709-6494","authenticated-orcid":true,"given":"Hui","family":"Chen","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Sun Yat-sen Memorial Hospital (T.W., T.L., W.L., P.L., H.C.), Sun Yat-sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1411-9526","authenticated-orcid":true,"given":"Jing","family":"Tan","sequence":"additional","affiliation":[{"name":"Guangdong Engineering &amp; Technology Research Center for Disease-Model Animals, Laboratory Animal Center (T.W., T.H., H.R., C.S., J.Q., X.F., J.W., S.X., Y.J., M.L., H.Z., Y.Z., K.L., Maoquan Yang, Z.S., X. 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