The Adipokine Hypothesis: Rethinking Heart Failure With Preserved Ejection Fraction | JACC | ESC 2025

Join Milton Packer, MD, FACC as he introduces the Adipokine Hypothesis—a groundbreaking framework for understanding heart failure with preserved ejection fraction (HFpEF). Drawing on decades of research, he explains how excess visceral adiposity alters adipokine biology, shifting from cardioprotective to pro-inflammatory signaling. This shift drives hypertrophy, inflammation, fibrosis, and ultimately HFpEF. Dr. Packer highlights striking parallels between obesity and HFpEF, reviews experimental and clinical evidence, and discusses how therapies—ranging from bariatric surgery to GLP-1 receptor agonists and SGLT2 inhibitors—restore adipokine balance and improve outcomes. Tune in for a thought-provoking exploration of how fat functions as the largest endocrine organ in the body and why it may hold the key to preventing and treating HFpEF.