Molecular Basis of Adipose–Cardiac Crosstalk in Cardiovascular Diseases: From Mechanisms to Therapeutic Opportunities

Figures

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  Figure 1. Heterogeneity of adipose tissue and its secretome in cardio-metabolic regulation. WAT, BAT, and beige/brite adipose tissue exhibit distinct metabolic and endocrine functions. WAT primarily serves as an energy reservoir and secretes adipokines that regulate metabolism and inflammation. In contrast, BAT is integral to adaptive thermogenesis and secretes cardioprotective batokines. Beige/brite adipose tissue demonstrates phenotypic plasticity, capable of interconverting between WAT- and BAT-like states. Cardiovascular-specific depots, such as EAT and PVAT, exert local modulatory effects on the heart and vascular system. Protective factors, including adiponectin, irisin, FGF21, and MFG-E8, enhance cardiac function, whereas dysregulated depots in the context of obesity or metabolic stress secrete pro-inflammatory cytokines (e.g., TNF-α, IL-6), pathogenic adipokines (e.g., leptin, resistin), and EVs (e.g., miR-221-3p), contributing to myocardial injury, vascular dysfunction, and atherosclerosis. Created by the authors using Figdraw 2.0.

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  Figure 2. Key molecular mechanisms underlying adipose–cardiac crosstalk. Adipose tissue secretes adipokines, EVs, metabolites, and proinflammatory cytokines, which travel through the bloodstream to the heart. These secretions, including visfatin, leptin, resistin, adiponectin, FABP4, and irisin, play a role in regulating inflammation, metabolism, and cardiovascular health, potentially impacting the heart. EVs may also act as pro-inflammatory mediators. Created by the authors using Figdraw.

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  Figure 3. Roles of adipose–cardiac crosstalk in major CVDs. Schematic overview of the pathological roles of adipose–cardiac crosstalk in CVDs. In atherosclerosis, adipose-derived cytokines, FFAs, and miRNAs promote endothelial dysfunction, lipid deposition, and plaque progression. In HF, EAT shifts toward a pro-inflammatory and pro-fibrotic phenotype, driving myocardial remodeling, apoptosis, and metabolic dysfunction. In hypertension-associated hypertrophy, VAT contributes to renin–angiotensin system activation, oxidative stress, and sympathetic overactivity, thereby increasing afterload and ventricular remodeling. In DCM, lipotoxicity, chronic inflammation, and AGE–RAGE signaling promote fibrosis and diastolic dysfunction. In AF, EAT-mediated inflammation, fatty infiltration, and electrical remodeling increase arrhythmogenic susceptibility and recurrence. Created by the authors using Figdraw.

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  Figure 4. Clinical and translational advances targeting the adipose–cardiac axis; Overview of clinical biomarkers, imaging tools, and therapeutic strategies related to adipose–heart crosstalk. Circulating markers such as the adiponectin/leptin ratio and EVs miRNAs (e.g., miR-146a, miR-126) reflect adipose dysfunction and cardiovascular risk. Multimodal imaging, including 18F-FDG PET-CT, cardiac CT, and MRI, enables quantification of adipose inflammation and EAT volume, providing incremental prognostic value. Pharmacological interventions (e.g., GLP-1RAs, SGLT2 inhibitors, anti–IL-1β therapy), metabolic surgery (e.g., RYGB), and emerging device-based or microbiota-targeted approaches modulate adipose inflammation and remodeling. Integration of lipidomics and AI-based imaging analysis further supports precision risk stratification and individualized cardiovascular therapy. Created by the authors using Figdraw.

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  Figure 5. Challenges and Future Directions in Adipose–Cardiac Crosstalk Research. The diagram illustrates key components in understanding the interactions between adipose tissue and the heart. It highlights the roles of adipokines in both pathological and protective contexts. The chart also emphasizes the integration of advanced technologies like single-cell sequencing, multicellular co-culture, organ-on-a-chip models, and protein labeling tracing to address bottlenecks and enhance therapeutic targeting. Future directions focus on multi-omics approaches, animal model validation, and the use of innovative protein tracing techniques, such as iSLET, to explore adipose–cardiac communication and potential biomarkers for disease treatment. Created by the authors using Figdraw.