# Metabo-epigenetic circuits of heart failure: chromatin-modifying enzymes as determinants of metabolic plasticity

## TL;DR

This paper explores how chromatin-modifying enzymes regulate heart metabolism and contribute to heart failure through epigenetic changes.

## Contribution

The paper introduces a new model of 'metabo-epigenetic circuitry' linking metabolic stress to cardiac gene regulation.

## Key findings

- Chromatin-modifying enzymes act as sensors and transducers of metabolic stress in the heart.
- Metabolic shifts drive epigenetic modifications that alter cardiac gene expression.
- These findings suggest new therapeutic targets for preventing heart failure.

## Abstract

Metabolic adaptations are a functional requirement for the heart to accommodate its broad range of physiologic operating conditions. It is increasingly recognized that persistent and exaggerated metabolic alterations precede adverse cardiac remodeling leading to heart failure. These metabolic shifts are coupled with changes in cardiac gene expression, driven in part by chromatin-modifying enzymes, which have recently been identified as both sensors and transducers of metabolic stress and gene regulatory networks, respectively. This review synthesizes the latest evidence implicating chromatin-modifying enzymes as key regulators of metabolic reprogramming in the heart, providing a framework to understand how metabolic stressors are incorporated as epigenetic modifications that regulate cardiac gene expression. We propose a model of ‘metabo-epigenetic circuitry’ within which energy metabolic perturbations drive transcriptional and epigenetic changes that ultimately contribute to cardiac dysfunction. Although many nodes in these circuits remain unidentified, this viewpoint opens new avenues for investigating chromatin-modifying enzymes as therapeutic targets to halt the metabolic programs that promote heart failure.

J Backs and colleagues summarize the latest evidence suggesting that chromatin-modifying enzymes are key regulators of heart metabolic reprogramming and provide a framework for understanding how metabolic stressors are incorporated as epigenetic modifications that regulate cardiac gene expression.