White Adipose Tissue in Obesity-Associated HFpEF: Insights From Mice and Humans

JACC Basic Transl Sci. 2025 May 8:101262. doi: 10.1016/j.jacbts.2025.02.021. Online ahead of print.

Abstract

Obesity and hypertension are prevalent comorbidities in heart failure with preserved ejection fraction (HFpEF). Increased adiposity is implicated in its pathophysiology. We investigated changes in white adipose tissue (WAT) in obesity-associated HFpEF utilizing patient samples and a murine model of obesity-associated HFpEF. WAT analysis revealed "browning", characterized by smaller adipocytes and increased UCP1 expression, alongside fibrosis and reduced vascular markers during acute HF decompensation. During chronic, stable HFpEF, "browning" markers declined. There is a dynamic process in WAT, where acute HF exacerbations trigger transient "browning", fibrosis, and vascular deterioration, which partially reverse but fibrosis persists. WAT dysfunction worsens during acute HF, highlighting a potential therapeutic target for obesity-related HFpEF.

Keywords: HFpEF; obesity; white adipose tissue; “browning,” fibrosis.