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Adipose tissue is now recognized as a heterogeneous endocrine and immunometabolic organ that actively communicates with the cardiovascular system through adipokines, inflammatory mediators, metabolites, and extracellular vesicles. Under physiological conditions, adipose\u2013cardiac crosstalk contributes to metabolic and cardiovascular homeostasis, whereas adipose tissue dysfunction promotes inflammation, fibrosis, endothelial injury, and cardiac remodeling. This review summarizes the heterogeneity of adipose depots and their secretomes, discusses the molecular mechanisms underlying adipose\u2013cardiac communication, and highlights their contributions to atherosclerosis, heart failure, hypertension, diabetic cardiomyopathy, and atrial fibrillation. We further discuss emerging biomarkers, therapeutic strategies, and precision medicine approaches targeting the adipose\u2013cardiac axis. Understanding depot-specific signaling networks may facilitate the development of novel diagnostic and therapeutic interventions for cardiometabolic diseases.<\/jats:p>","DOI":"10.3390\/biom16081093","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T05:49:27Z","timestamp":1785131367000},"page":"1093","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular Basis of Adipose\u2013Cardiac Crosstalk in Cardiovascular Diseases: From Mechanisms to Therapeutic Opportunities"],"prefix":"10.3390","volume":"16","author":[{"given":"Siqi","family":"Gan","sequence":"first","affiliation":[{"name":"Xi\u2019an Key Laboratory of Stem Cell and Regenerative Medicine, School of Life Science and Technology, Northwestern Polytechnical University, Xi\u2019an 710072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qixuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Xi\u2019an Key Laboratory of Stem Cell and Regenerative Medicine, School of Life Science and Technology, Northwestern Polytechnical University, Xi\u2019an 710072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Xi\u2019an Key Laboratory of Stem Cell and Regenerative Medicine, School of Life Science and Technology, Northwestern Polytechnical University, Xi\u2019an 710072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9079-8826","authenticated-orcid":false,"given":"Li","family":"Yan","sequence":"additional","affiliation":[{"name":"Xi\u2019an Key Laboratory of Stem Cell and Regenerative Medicine, School of Life Science and Technology, Northwestern Polytechnical University, Xi\u2019an 710072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic Medicine, Fourth Military Medical University, Xi\u2019an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1893-0658","authenticated-orcid":false,"given":"Heng","family":"Ma","sequence":"additional","affiliation":[{"name":"Xi\u2019an Key Laboratory of Stem Cell and Regenerative Medicine, School of Life Science and Technology, Northwestern Polytechnical University, Xi\u2019an 710072, China"},{"name":"Department of Physiology and Pathophysiology, School of Basic Medicine, Fourth Military Medical University, Xi\u2019an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Xi\u2019an Key Laboratory of Stem Cell and Regenerative Medicine, School of Life Science and Technology, Northwestern Polytechnical University, Xi\u2019an 710072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"ref_1","first-page":"e471","article-title":"Gene Therapy in Cardiovascular Disease: Recent Advances and Future Directions in Science: A Science Advisory from the American Heart Association","volume":"150","author":"Kim","year":"2024","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3388","DOI":"10.1093\/eurheartj\/ehab454","article-title":"Association between Adiposity and Cardiovascular Outcomes: An Umbrella Review and Meta-Analysis of Observational and Mendelian Randomization Studies","volume":"42","author":"Kim","year":"2021","journal-title":"Eur. 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