{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T23:19:17Z","timestamp":1788477557940,"version":"build-2803163510"},"reference-count":194,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Metabolic dysfunction\u2013associated steatotic liver disease (MASLD) and heart failure with preserved ejection fraction (HFpEF) are increasingly prevalent cardiometabolic disorders that frequently coexist in clinical practice. Growing evidence indicates that MASLD is associated with an increased risk of heart failure, with emerging data suggesting particular relevance to the HFpEF phenotype. This relationship is supported by several shared pathophysiological mechanisms, including insulin resistance, lipotoxicity, chronic low-grade inflammation, neurohormonal activation, microvascular dysfunction, fibrotic remodeling, and dysregulation of the gut\u2013heart\u2013liver axis, collectively supporting the concept of a heart\u2013liver metabolic axis linking hepatic and cardiac injury. Clinically, MASLD, especially when accompanied by a greater fibrosis burden, may help identify a metabolically enriched HFpEF subgroup characterized by more advanced systemic derangement and organ remodeling. Although lifestyle intervention, sodium\u2013glucose cotransporter 2 (SGLT2) inhibitors, incretin-based therapies, and liver-directed treatments have broadened the therapeutic framework for this overlap phenotype, prospective evidence specifically addressing patients with coexisting MASLD and HFpEF remains limited. This review summarizes the epidemiological links, shared mechanisms, risk stratification approaches, and therapeutic strategies relevant to the coexistence of MASLD and HFpEF.<\/jats:p>","DOI":"10.3389\/fphar.2026.1863710","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T05:00:42Z","timestamp":1779944442000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Metabolic dysfunction\u2013associated steatotic liver disease and heart failure with preserved ejection fraction: mechanisms and clinical implications from a heart\u2013liver metabolic axis perspective"],"prefix":"10.3389","volume":"17","author":[{"given":"Xuebi","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Clinical Medicine, North Sichuan Medical College","place":["Nanchong, Sichuan, China"]},{"name":"Department of Cardiac and Great Vascular Surgery, Suining Central Hospital","place":["Suining, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongxin","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, North Sichuan Medical College","place":["Nanchong, Sichuan, China"]},{"name":"Department of Cardiac and Great Vascular Surgery, Suining Central Hospital","place":["Suining, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueshi","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, North Sichuan Medical College","place":["Nanchong, Sichuan, China"]},{"name":"Department of Cardiac and Great Vascular Surgery, Suining Central Hospital","place":["Suining, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianping","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiac and Great Vascular Surgery, Suining Central Hospital","place":["Suining, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiac and Great Vascular Surgery, Suining Central Hospital","place":["Suining, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"E130","DOI":"10.1152\/ajpendo.00158","article-title":"Insulin signaling in the heart","volume":"321","author":"Abel","year":"2021","journal-title":"Am. 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