{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:44:45Z","timestamp":1791391485499,"version":"4.3.3"},"reference-count":180,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Obesity, sarcopenia, and heart failure with preserved ejection fraction (HFpEF) constitute an interconnected clinical triad driven by multisystem mechanisms centered on the adipokine axis. Adipose tissue, now recognized as a dynamic endocrine organ, undergoes pathological remodeling in obesity, characterized by hypoxia, chronic low-grade inflammation, and dysregulated adipokine secretion. These changes impair endothelial function, promote myocardial fibrosis, and disrupt skeletal muscle metabolism, thereby linking cardiometabolic and musculoskeletal dysfunction. This review integrates current evidence on homeostatic adipokines, such as adiponectin, apelin, and omentin, that preserve vascular and muscular resilience, as well as stress-inducible adipokines, such as leptin, resistin, and GDF15, that reflect or amplify metabolic and inflammatory injury. A maladaptive adipokine milieu associates with a self-reinforcing cycle of endothelial dysfunction, myocardial stiffening, and muscle atrophy that characterizes s HFpEF in the context of obesity and sarcopenia. We further discuss emerging translational applications, including diagnostic and prognostic adipokine signatures, targeted modulation of adipokine pathways, and the therapeutic impact of GLP-1 receptor agonists on adipose\u2013cardiovascular\u2013muscle crosstalk. Remaining challenges, including the adiponectin paradox and pleiotropic adipokine effects, highlight the need for precision-medicine approaches integrating multimodal biomarker profiling with cardiometabolic and musculoskeletal phenotyping.<\/jats:p>","DOI":"10.3390\/ijms27020612","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T11:46:43Z","timestamp":1767786403000},"page":"612","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The Adipokine Axis in Heart Failure: Linking Obesity, Sarcopenia and Cardiac Dysfunction in HFpEF"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0616-9101","authenticated-orcid":false,"given":"Luka","family":"Komi\u0107","sequence":"first","affiliation":[{"name":"Department of Family Medicine, Split-Dalmatia County Health Center, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3536-2713","authenticated-orcid":false,"given":"Jelena","family":"Komi\u0107","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, Split-Dalmatia County Health Center, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3452-389X","authenticated-orcid":false,"given":"Nikola","family":"Pavlovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, University of Split School of Medicine, 21000 Split, Croatia"},{"name":"Laboratory for Cardiometabolic Research, University of Split School of Medicine, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9696-3359","authenticated-orcid":false,"given":"Marko","family":"Kumri\u0107","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, University of Split School of Medicine, 21000 Split, Croatia"},{"name":"Laboratory for Cardiometabolic Research, University of Split School of Medicine, 21000 Split, Croatia"},{"name":"Department of Cardiovascular Diseases, University Hospital of Split, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9316-5538","authenticated-orcid":false,"given":"Josipa","family":"Buki\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Split School of Medicine, 21000 Split, Croatia"},{"name":"Department of Laboratory Medicine and Pharmacy, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"Jeron\u010di\u0107 Tomi\u0107","sequence":"additional","affiliation":[{"name":"Department of Public Health, University of Split School of Medicine, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1634-0635","authenticated-orcid":false,"given":"Jo\u0161ko","family":"Bo\u017ei\u0107","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, University of Split School of Medicine, 21000 Split, Croatia"},{"name":"Laboratory for Cardiometabolic Research, University of Split School of Medicine, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,7]]},"reference":[{"key":"ref_1","first-page":"204","article-title":"Obesity in reproduction: Mechanisms from fertilization to post-uterine development (Review)","volume":"56","year":"2025","journal-title":"Int. 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