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For example, adipose tissue\u2013driven inflammation contributes to the development of other cardiometabolic comorbidities, such as hypertension, leading to left ventricular pressure overload and adverse remodeling of the heart. Adipose tissue also functions as an endocrine organ, and altered secretion of proteins, lipid mediators, metabolites, and small extracellular vesicles (collectively referred to as the secretome) from dysfunctional fat can lead to cardiac inflammation and oxidative stress, which drive changes in structure and function of the heart. In this review, we begin with an overview of current therapies for obesity and what is known about how they influence the heart. Then we focus on mechanisms by which fat communicates with the heart via secreted factors and highlight druggable nodes in this circuit that could be exploited to develop next-generation therapies for heart failure.<\/jats:p>","DOI":"10.1161\/circresaha.125.325593","type":"journal-article","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T18:00:24Z","timestamp":1747936824000},"page":"1363-1381","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["Modulating the Secretome of Fat to Treat Heart Failure"],"prefix":"10.1161","volume":"136","author":[{"given":"Lorien G.","family":"Salyer","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Medicine (L.G.S., T.A.M.), University of Colorado Anschutz Medical Campus, Aurora, CO."},{"name":"Consortium for Fibrosis Research &amp; Translation (L.G.S., T.A.M.), University of Colorado Anschutz Medical Campus, Aurora, CO."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6358-6948","authenticated-orcid":true,"given":"Yajing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL (Y.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9041-0876","authenticated-orcid":true,"given":"Xinliang","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA (X.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0938-9986","authenticated-orcid":true,"given":"Anna","family":"Foryst-Ludwig","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, Max Rubner Center for Cardiovascular Metabolic Renal Research (MRC), Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, Germany (A.F.-L., U.K.)."},{"name":"DZHK (German Centre for Cardiovascular Research), Berlin, Germany (A.F.-L., U.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7386-0990","authenticated-orcid":true,"given":"Ulrich","family":"Kintscher","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, Max Rubner Center for Cardiovascular Metabolic Renal Research (MRC), Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, Germany (A.F.-L., U.K.)."},{"name":"DZHK (German Centre for Cardiovascular Research), Berlin, Germany (A.F.-L., U.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1588-1512","authenticated-orcid":true,"given":"Saravanakkumar","family":"Chennappan","sequence":"additional","affiliation":[{"name":"Department of Biomedical Research and Translational Medicine, Masonic Medical Research Institute, Utica, NY (S.C., M.I.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6121-0533","authenticated-orcid":true,"given":"Maria I.","family":"Kontaridis","sequence":"additional","affiliation":[{"name":"Department of Biomedical Research and Translational Medicine, Masonic Medical Research Institute, Utica, NY (S.C., M.I.K.)."},{"name":"Division of Cardiology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA (M.I.K.)."},{"name":"Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA (M.I.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7778-4470","authenticated-orcid":true,"given":"Timothy A.","family":"McKinsey","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine (L.G.S., T.A.M.), University of Colorado Anschutz Medical Campus, Aurora, CO."},{"name":"Consortium for Fibrosis Research &amp; Translation (L.G.S., T.A.M.), University of Colorado Anschutz Medical Campus, Aurora, CO."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","first-page":"1","article-title":"Prevalence of obesity and severe obesity among adults: United States, 2017-2018.","author":"Hales CM","year":"2020","unstructured":"Hales CM, Carroll MD, Fryar CD, Ogden CL. 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