Metabolic rewiring and inter-organ crosstalk in diabetic HFpEF
Abstract Heart failure with preserved ejection fraction (HFpEF) represents a significant and growing clinical challenge. Initially, for an extended period, HFpEF was simply considered as a subset of heart failure, manifesting as haemodynamic disorders such as hypertension, myocardial hypertrophy, an...
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BMC
2025-04-01
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| Series: | Cardiovascular Diabetology |
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| Online Access: | https://doi.org/10.1186/s12933-025-02707-7 |
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| author | Lingyun Luo Yuyue Zuo Lei Dai |
| author_facet | Lingyun Luo Yuyue Zuo Lei Dai |
| author_sort | Lingyun Luo |
| collection | DOAJ |
| description | Abstract Heart failure with preserved ejection fraction (HFpEF) represents a significant and growing clinical challenge. Initially, for an extended period, HFpEF was simply considered as a subset of heart failure, manifesting as haemodynamic disorders such as hypertension, myocardial hypertrophy, and diastolic dysfunction. However, the rising prevalence of obesity and diabetes has reshaped the HFpEF phenotype, with nearly 45% of cases coexisting with diabetes. Currently, it is recognized as a multi-system disorder that involves the heart, liver, kidneys, skeletal muscle, adipose tissue, along with immune and inflammatory signaling pathways. In this review, we summarize the landscape of metabolic rewiring and the crosstalk between the heart and other organs/systems (e.g., adipose, gut, liver and hematopoiesis system) in diabetic HFpEF for the first instance. A diverse array of metabolites and cytokines play pivotal roles in this intricate crosstalk process, with metabolic rewiring, chronic inflammatory responses, immune dysregulation, endothelial dysfunction, and myocardial fibrosis identified as the central mechanisms at the heart of this complex interplay. The liver-heart axis links nonalcoholic steatohepatitis and HFpEF through shared lipid accumulation, inflammation, and fibrosis pathways, while the gut-heart axis involves dysbiosis-driven metabolites (e.g., trimethylamine N-oxide, indole-3-propionic acid and short-chain fatty acids) impacting cardiac function and inflammation. Adipose-heart crosstalk highlights epicardial adipose tissue as a source of local inflammation and mechanical stress, whereas the hematopoietic system contributes via immune cell activation and cytokine release. We contend that, based on the viewpoints expounded in this review, breaking this inter-organ/system vicious cycle is the linchpin of treating diabetic HFpEF. Graphical abstract |
| format | Article |
| id | doaj-art-c8d7a67c767d40c69b8caec8cc43c531 |
| institution | OA Journals |
| issn | 1475-2840 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Cardiovascular Diabetology |
| spelling | doaj-art-c8d7a67c767d40c69b8caec8cc43c5312025-08-20T01:53:19ZengBMCCardiovascular Diabetology1475-28402025-04-0124111410.1186/s12933-025-02707-7Metabolic rewiring and inter-organ crosstalk in diabetic HFpEFLingyun Luo0Yuyue Zuo1Lei Dai2Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of DermatologyDepartment of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstract Heart failure with preserved ejection fraction (HFpEF) represents a significant and growing clinical challenge. Initially, for an extended period, HFpEF was simply considered as a subset of heart failure, manifesting as haemodynamic disorders such as hypertension, myocardial hypertrophy, and diastolic dysfunction. However, the rising prevalence of obesity and diabetes has reshaped the HFpEF phenotype, with nearly 45% of cases coexisting with diabetes. Currently, it is recognized as a multi-system disorder that involves the heart, liver, kidneys, skeletal muscle, adipose tissue, along with immune and inflammatory signaling pathways. In this review, we summarize the landscape of metabolic rewiring and the crosstalk between the heart and other organs/systems (e.g., adipose, gut, liver and hematopoiesis system) in diabetic HFpEF for the first instance. A diverse array of metabolites and cytokines play pivotal roles in this intricate crosstalk process, with metabolic rewiring, chronic inflammatory responses, immune dysregulation, endothelial dysfunction, and myocardial fibrosis identified as the central mechanisms at the heart of this complex interplay. The liver-heart axis links nonalcoholic steatohepatitis and HFpEF through shared lipid accumulation, inflammation, and fibrosis pathways, while the gut-heart axis involves dysbiosis-driven metabolites (e.g., trimethylamine N-oxide, indole-3-propionic acid and short-chain fatty acids) impacting cardiac function and inflammation. Adipose-heart crosstalk highlights epicardial adipose tissue as a source of local inflammation and mechanical stress, whereas the hematopoietic system contributes via immune cell activation and cytokine release. We contend that, based on the viewpoints expounded in this review, breaking this inter-organ/system vicious cycle is the linchpin of treating diabetic HFpEF. Graphical abstracthttps://doi.org/10.1186/s12933-025-02707-7HFpEFDiabetesMetabolismInflammationInter-organ crosstalk |
| spellingShingle | Lingyun Luo Yuyue Zuo Lei Dai Metabolic rewiring and inter-organ crosstalk in diabetic HFpEF Cardiovascular Diabetology HFpEF Diabetes Metabolism Inflammation Inter-organ crosstalk |
| title | Metabolic rewiring and inter-organ crosstalk in diabetic HFpEF |
| title_full | Metabolic rewiring and inter-organ crosstalk in diabetic HFpEF |
| title_fullStr | Metabolic rewiring and inter-organ crosstalk in diabetic HFpEF |
| title_full_unstemmed | Metabolic rewiring and inter-organ crosstalk in diabetic HFpEF |
| title_short | Metabolic rewiring and inter-organ crosstalk in diabetic HFpEF |
| title_sort | metabolic rewiring and inter organ crosstalk in diabetic hfpef |
| topic | HFpEF Diabetes Metabolism Inflammation Inter-organ crosstalk |
| url | https://doi.org/10.1186/s12933-025-02707-7 |
| work_keys_str_mv | AT lingyunluo metabolicrewiringandinterorgancrosstalkindiabetichfpef AT yuyuezuo metabolicrewiringandinterorgancrosstalkindiabetichfpef AT leidai metabolicrewiringandinterorgancrosstalkindiabetichfpef |