Yue Yang, Qian Hu, Hongxin Kang, Long Xie, Yue Hu, Juan Li, Xianlin Zhao, Lv Zhu, Wenfu Tang, Jingping Liu, Christopher J Lyon, Meihua Wan
{"title":"中药自噬驱动的脂质调节可减轻重症急性胰腺炎的心脏脂肪毒性。","authors":"Yue Yang, Qian Hu, Hongxin Kang, Long Xie, Yue Hu, Juan Li, Xianlin Zhao, Lv Zhu, Wenfu Tang, Jingping Liu, Christopher J Lyon, Meihua Wan","doi":"10.7150/thno.117243","DOIUrl":null,"url":null,"abstract":"<p><p><b>Rationale:</b> Myocardial injury is a common and life-threatening complication of severe acute pancreatitis (SAP) and is driven primarily by metabolic disturbances. This study aimed to elucidate the pathogenesis of SAP-induced cardiac injury (SACI) and to identify effective therapeutic strategies. <b>Methods:</b> Untargeted metabolomics and proteomics analyses were employed to identify metabolic pathways and proteins associated with myocardial injury in SACI mouse model. Histological and Western blot assays were used to assess lipid droplet (LD) accumulation, the expression of autophagy markers, and LD-autophagosome colocalization. The traditional Chinese medicine formula Taohong Siwu Decoction (THSWD) was tested for its therapeutic potential in a SACI mouse model and a SACI cardiomyocyte model established by incubating primary mouse cardiomyocytes with serum from the SACI mouse model. These SACI cardiomyocytes cultures were then treated with serum from control or THSWD-treated mice, with or without autophagy inhibitors, and analyzed for effects on lipophagy, mitochondrial structure and function, long-chain fatty acid metabolism, and oxidative stress. <b>Results:</b> SAP-induced myocardial injury was characterized by disrupted lipid metabolism, leading to abnormal cardiomyocyte LD accumulation and structural and functional deficiencies in their mitochondria. THSWD treatment reduced LD accumulation, restored LD-autophagosome colocalization, and increased mitochondrial structural integrity, membrane potential, and fatty acid β-oxidation. However, these THSWD effects were abolished in the presence of an autophagy inhibitor, implying they occur via a lipophagy-dependent mechanism. <b>Conclusion:</b> Excessive LD accumulation drives mitochondrial dysfunction, contributing to SAP-induced myocardial lipotoxicity. THSWD promotes lipophagy to mitigate lipid accumulation and restore mitochondrial function, and may serve as an effective therapeutic strategy for SAP-induced cardiac metabolic disorders and mitochondrial dysfunction.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 17","pages":"8822-8839"},"PeriodicalIF":13.3000,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439263/pdf/","citationCount":"0","resultStr":"{\"title\":\"Autophagy-driven lipid regulation by an herbal decoction alleviates cardiac lipotoxicity in severe acute pancreatitis.\",\"authors\":\"Yue Yang, Qian Hu, Hongxin Kang, Long Xie, Yue Hu, Juan Li, Xianlin Zhao, Lv Zhu, Wenfu Tang, Jingping Liu, Christopher J Lyon, Meihua Wan\",\"doi\":\"10.7150/thno.117243\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><b>Rationale:</b> Myocardial injury is a common and life-threatening complication of severe acute pancreatitis (SAP) and is driven primarily by metabolic disturbances. This study aimed to elucidate the pathogenesis of SAP-induced cardiac injury (SACI) and to identify effective therapeutic strategies. <b>Methods:</b> Untargeted metabolomics and proteomics analyses were employed to identify metabolic pathways and proteins associated with myocardial injury in SACI mouse model. Histological and Western blot assays were used to assess lipid droplet (LD) accumulation, the expression of autophagy markers, and LD-autophagosome colocalization. The traditional Chinese medicine formula Taohong Siwu Decoction (THSWD) was tested for its therapeutic potential in a SACI mouse model and a SACI cardiomyocyte model established by incubating primary mouse cardiomyocytes with serum from the SACI mouse model. These SACI cardiomyocytes cultures were then treated with serum from control or THSWD-treated mice, with or without autophagy inhibitors, and analyzed for effects on lipophagy, mitochondrial structure and function, long-chain fatty acid metabolism, and oxidative stress. <b>Results:</b> SAP-induced myocardial injury was characterized by disrupted lipid metabolism, leading to abnormal cardiomyocyte LD accumulation and structural and functional deficiencies in their mitochondria. THSWD treatment reduced LD accumulation, restored LD-autophagosome colocalization, and increased mitochondrial structural integrity, membrane potential, and fatty acid β-oxidation. However, these THSWD effects were abolished in the presence of an autophagy inhibitor, implying they occur via a lipophagy-dependent mechanism. <b>Conclusion:</b> Excessive LD accumulation drives mitochondrial dysfunction, contributing to SAP-induced myocardial lipotoxicity. THSWD promotes lipophagy to mitigate lipid accumulation and restore mitochondrial function, and may serve as an effective therapeutic strategy for SAP-induced cardiac metabolic disorders and mitochondrial dysfunction.</p>\",\"PeriodicalId\":22932,\"journal\":{\"name\":\"Theranostics\",\"volume\":\"15 17\",\"pages\":\"8822-8839\"},\"PeriodicalIF\":13.3000,\"publicationDate\":\"2025-08-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439263/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Theranostics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.7150/thno.117243\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Theranostics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.7150/thno.117243","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Autophagy-driven lipid regulation by an herbal decoction alleviates cardiac lipotoxicity in severe acute pancreatitis.
Rationale: Myocardial injury is a common and life-threatening complication of severe acute pancreatitis (SAP) and is driven primarily by metabolic disturbances. This study aimed to elucidate the pathogenesis of SAP-induced cardiac injury (SACI) and to identify effective therapeutic strategies. Methods: Untargeted metabolomics and proteomics analyses were employed to identify metabolic pathways and proteins associated with myocardial injury in SACI mouse model. Histological and Western blot assays were used to assess lipid droplet (LD) accumulation, the expression of autophagy markers, and LD-autophagosome colocalization. The traditional Chinese medicine formula Taohong Siwu Decoction (THSWD) was tested for its therapeutic potential in a SACI mouse model and a SACI cardiomyocyte model established by incubating primary mouse cardiomyocytes with serum from the SACI mouse model. These SACI cardiomyocytes cultures were then treated with serum from control or THSWD-treated mice, with or without autophagy inhibitors, and analyzed for effects on lipophagy, mitochondrial structure and function, long-chain fatty acid metabolism, and oxidative stress. Results: SAP-induced myocardial injury was characterized by disrupted lipid metabolism, leading to abnormal cardiomyocyte LD accumulation and structural and functional deficiencies in their mitochondria. THSWD treatment reduced LD accumulation, restored LD-autophagosome colocalization, and increased mitochondrial structural integrity, membrane potential, and fatty acid β-oxidation. However, these THSWD effects were abolished in the presence of an autophagy inhibitor, implying they occur via a lipophagy-dependent mechanism. Conclusion: Excessive LD accumulation drives mitochondrial dysfunction, contributing to SAP-induced myocardial lipotoxicity. THSWD promotes lipophagy to mitigate lipid accumulation and restore mitochondrial function, and may serve as an effective therapeutic strategy for SAP-induced cardiac metabolic disorders and mitochondrial dysfunction.
期刊介绍:
Theranostics serves as a pivotal platform for the exchange of clinical and scientific insights within the diagnostic and therapeutic molecular and nanomedicine community, along with allied professions engaged in integrating molecular imaging and therapy. As a multidisciplinary journal, Theranostics showcases innovative research articles spanning fields such as in vitro diagnostics and prognostics, in vivo molecular imaging, molecular therapeutics, image-guided therapy, biosensor technology, nanobiosensors, bioelectronics, system biology, translational medicine, point-of-care applications, and personalized medicine. Encouraging a broad spectrum of biomedical research with potential theranostic applications, the journal rigorously peer-reviews primary research, alongside publishing reviews, news, and commentary that aim to bridge the gap between the laboratory, clinic, and biotechnology industries.