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

María Valero-Muñoz; Eng Leng Saw; Hannah Cooper; David R Pimentel; Flora Sam

doi:10.1016/j.jacbts.2025.02.021

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.

Authors

María Valero-Muñoz¹, Eng Leng Saw¹, Hannah Cooper¹, David R Pimentel¹, Flora Sam²

Affiliations

¹ Whitaker Cardiovascular Institute, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts, USA.
² Whitaker Cardiovascular Institute, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts, USA. Electronic address: florasam@bu.edu.

PMID: 40338771
DOI: 10.1016/j.jacbts.2025.02.021

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.