# Targeting Adipose Tissue Function Protects Against Heart Failure with Preserved Ejection Fraction

## TL;DR

This study shows that activating fat tissue can protect the heart in obesity-related heart failure.

## Contribution

The study identifies the adipose-heart axis as a novel therapeutic target for heart failure with preserved ejection fraction.

## Key findings

- Activating thermogenic adipose tissue improves cardiac function and protects against HFpEF.
- Transplanting thermogenic adipose tissue from treated mice provides cardioprotection.
- Genetic enhancement of thermogenic adipose tissue improves heart structure and function.

## Abstract

This study seeks to develop a better understanding of how the targeting of adipose tissue (AT) can mediate outcomes in cardiac function. Obesity is highly prevalent among individuals with heart failure with preserved ejection fraction (HFpEF). While thermogenic AT helps counteract obesity‐related conditions, its impact on heart function in obesity‐related HFpEF is unclear. Using a “two‐hit” HFpEF model, the study evaluates the impact of thermogenic AT on cardiac function through pharmacological, surgical, and genetic interventions. Activation of thermogenic AT via the β3‐adrenergic receptor agonist CL‐316,243 (CL) improves cardiac function, protects against HFpEF‐induced remodeling, and enhances energy expenditure. Similarly, transplantation of AT from CL‐treated mice into wild‐type recipients confers cardioprotection. In contrast, genetic suppression of thermogenesis (Adipoq‐Cre; Prdm16
fl/fl) abolishes CL's benefits, while genetic enhancement of thermogenic AT (Ucp1‐CreERT2; Cdkn2a
fl/fl) improves cardiac structure and function. Mechanistically, AT thermogenesis is linked with significant alterations in the cardiac lipidome, as revealed by lipidomic analysis via LC/MS‐MS. These findings establish the adipose‐heart axis as a promising therapeutic target for obesity‐related HFpEF and cardiometabolic health.

This study explores the role adipose tissue (AT) phenotypes have in determining cardiovascular outcomes in an obesity‐related heart failure with preserved ejection fraction (HFpEF) model. Pharmacological induction of thermogenesis promoted resilience to HFpEF‐induced remodeling of AT and conferred cardioprotection. Surgical and genetic models confirmed cardioprotection was mediated through AT. Mechanistically, AT targeting was linked with alterations in the cardiac lipidome.