[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-457718-105":59,"doc-detail-457718-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","succinategpr91-signaling-promotes-cardiomyocyte-metabolic-reprogramming-and-nad-production-to-alleviate-hfpef","Succinate–GPR91 signaling promotes cardiomyocyte metabolic reprogramming and NAD+ production to alleviate HFpEF","","Disrupted cardiomyocyte energy metabolism is a hallmark of heart failure with preserved ejection fraction (HFpEF), where the TCA-cycle intermediate succinate is markedly reduced. Beyond metabolism, succinate signals through GPR91 (SUCNR1) to coordinate metabolic and immune pathways, yet the cardiomyocyte-specific succinate–GPR91 mechanisms in HFpEF remain insufficiently defined. In mouse HFpEF models and human AC16 cardiomyocytes, succinate restores metabolism and diastolic function via Gq-AMPK signaling and boosts cardiomyocyte NAD+ production.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/succinategpr91-signaling-promotes-cardiomyocyte-metabolic-reprogramming-and-nad-production-to-alleviate-hfpef/457718/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/succinategpr91-signaling-promotes-cardiomyocyte-metabolic-reprogramming-and-nad-production-to-alleviate-hfpef/457718.png","ImageObject",300,407,{"name":92,"@type":93},"awa","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-09","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":24},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What problem does the study address in HFpEF?","Question",{"text":112,"@type":113},"It addresses impaired cardiomyocyte energy metabolism in HFpEF and the reduced succinate level that may weaken succinate–GPR91 signaling.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were HFpEF models and GPR91 perturbations designed?",{"text":117,"@type":113},"HFpEF models were generated in wild-type mice, global GPR91 knockout mice, and cardiomyocyte-specific GPR91 knockout mice, with or without succinate supplementation.",{"name":119,"@type":110,"acceptedAnswer":120},"What key mechanism connects succinate–GPR91 to cardiomyocyte metabolism?",{"text":121,"@type":113},"Succinate activates Gq-mediated signaling to enhance AMPK phosphorylation and increases NAD+ production, promoting metabolic reprogramming.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},457718,1790789378,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":24,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},3985747858093,"https://ap-avatar.wpscdn.com/davatar_3d24733baf745e90a7e4bdd5f77d97b2","Jia et al. Cardiovascular Diabetology (2026) 25:5 [https://doi.org/10.1186/s12933-025-03030-x](https://doi.org/10.1186/s12933-025-03030-x)  \nCardiovascular Diabetology  \nRESEARCH Open Access  \nSuccinate–GPR91 signaling promotes cardiomyocyte metabolic reprogramming and NAD+ production to alleviate HFpEF  \nYumeng Jia 1, Wenhui Niu 1, Lu Liu 1, Qun Zhang2, Dingwei Li 1, Tangyu Dai 1, Jie Du3,4*† and Lei Wang 1*†  \nAbstract  \nBackground Disrupted cardiomyocyte energy metabolism is a hallmark of heart failure with preserved ejection fraction (HFpEF) . Succinate, a key intermediate of the tricarboxylic acid cycle, is markedly decreased in HFpEF myocardium. In addition to its metabolic role, succinate functions as a signaling molecule that activates GPR91 to regulate metabolic and immune pathways. However, the precise contributions and mechanisms of cardiomyocyte succinate–GPR91 signaling in HFpEF pathogenesis remain incompletely understood.  \nMethods HFpEF models were established in wild-type (WT), global GPR91 knockout (Gpr91-/-), and cardiomyocytespecific GPR91 knockout (Gpr91ΔCM) mice, with or without succinate supplementation. Cardiac structure, function, and metabolic phenotypes were assessed using echocardiography, histology, and molecular assays. Transcriptome sequencing of myocardial tissues was performed to identify pathways regulated by succinate–GPR91 signaling. Mechanistic studies in human AC16 cardiomyocytes were conducted to validate pathway regulation and clarify downstream molecular mechanisms. Additionally, rescue experiments were performed to confirm the functional relevance of succinate–GPR91 signaling in cardiomyocyte metabolism and HFpEF progression.  \nResults Cardiac succinate levels and GPR91 expression were markedly decreased in HFpEF mice. Succinate supplementation restored systemic metabolism, improved diastolic function, and attenuated myocardial hypertrophy and fibrosis in WT HFpEF mice, whereas these protective effects were abolished in both Gpr91-/- and Gpr91ΔCM mice. Transcriptomic analysis demonstrated that succinate activated AMPK signaling and enriched pathways related to glucose–lipid metabolism and NAD+ biosynthesis in Gpr91fl/fl but not in Gpr91ΔCM hearts. Mechanistically, succinate enhanced AMPK phosphorylation and NAD+ production via Gq-mediated signaling, thereby promoting cardiomyocyte metabolic reprogramming.  \nConclusion These findings identify the succinate–GPR91 axis as a critical regulator of cardiometabolic homeostasis and a potential therapeutic target in HFpEF.  \n†Jie Du and Lei Wang contributed equally to this work.  \n*Correspondence:  \nJie Du [jiedu@ccmu.edu.cn](jiedu@ccmu.edu.cn)[ ](jiedu@ccmu.edu.cn)Lei Wang [lei.wang2@ccmu.edu.cn](lei.wang2@ccmu.edu.cn)  \nFull list of author information is available at the end of the article  \n© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creati](http://creati)[vecommons.org/l](vecommons.org/l)icenses/by-nc-nd/4.0/.  \nJia et al. Cardiovascular Diabetology (2026) 25:5 Page 2 of 18  \nKeywords Succinate, GPR91,","cbCainLaxhl1hQ5W","https://ap.wps.com/l/cbCainLaxhl1hQ5W","pdf",3027471,18,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusion\n## Keywords","[{\"question\":\"What problem does the study address in HFpEF?\",\"answer\":\"It addresses impaired cardiomyocyte energy metabolism in HFpEF and the reduced succinate level that may weaken succinate–GPR91 signaling.\"},{\"question\":\"How were HFpEF models and GPR91 perturbations designed?\",\"answer\":\"HFpEF models were generated in wild-type mice, global GPR91 knockout mice, and cardiomyocyte-specific GPR91 knockout mice, with or without succinate supplementation.\"},{\"question\":\"What key mechanism connects succinate–GPR91 to cardiomyocyte metabolism?\",\"answer\":\"Succinate activates Gq-mediated signaling to enhance AMPK phosphorylation and increases NAD+ production, promoting metabolic reprogramming.\"}]","Succinate–GPR91 signaling promotes cardiomyocyte metabolic reprogramming and NAD+ production to alleviate HFpEF | PDF",1790750222,45]