Heart failure with preserved ejection fraction (HFpEF) has long lacked a unifying biological explanation—until now. In this presentation, Dr. Milton Packer introduces The Adipokine Hypothesis, a new framework that links visceral adiposity to the onset and progression of HFpEF through endocrine signaling between adipose tissue and the heart. Dr. Packer describes how visceral fat acts as an active endocrine organ, releasing adipokines that influence inflammation, fibrosis, and cardiac remodeling. He explains the roles of three major adipokine domains - protective, compensatory, and pathological—and how imbalances between them drive disease development.