Dietary branched-chain amino acids get to the heart of H3K23Pr
Christina Demetriadou, … , Daniel S. Kantner, Nathaniel W. Snyder
Christina Demetriadou, … , Daniel S. Kantner, Nathaniel W. Snyder
Published November 15, 2023
Citation Information: J Clin Invest. 2023;133(22):e174953. https://doi.org/10.1172/JCI174953.
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Commentary

Dietary branched-chain amino acids get to the heart of H3K23Pr

Abstract

Cardiac metabolism provides effects that extend beyond the transformation of energy for the heart to operate effectively. Some metabolites also function as signaling molecules and exert transcriptional changes. Heart failure is a progressive pathology in which these metabolite functions falter. In this issue of the JCI, Yang et al. describe a protective effect from a low–branched chain amino acid (BCAA) diet in a mouse model of heart failure. The findings implicate a propionylation mark on histone H3 lysine 23 (H3K23Pr), previously shown to be dependent on the BCAA isoleucine, in transcriptional control of the cardiac stress response. The result underscores the interplay between metabolism and histone acylation, highlighting targeted dietary and pharmacological intervention as a means to decelerate cardiac hypertrophy.

Authors

Christina Demetriadou, Daniel S. Kantner, Nathaniel W. Snyder

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Figure 1

Yang et al. (6) demonstrate a cardioprotective role of a BCAA-free diet in a mouse model of heart failure.

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Yang et al. (6) demonstrate a cardioprotective role of a BCAA-free diet ...
Hearts from mice fed a standard BCAA diet and subjected to short-term pressure overload exhibited enrichment of propionylation on H3K23Pr at the promoters of specific workload-dependent genes. Enrichment of H3K23Pr correlated with increased expression of ECM and proliferation genes, as well as reduced transcription of metabolic and ETC genes relative to unstressed hearts. The pressure overload–induced enrichment of H3K23Pr at those loci was prevented in mice fed a diet lacking BCAAs, which also restored gene expression changes and inhibited cardiac hypertrophy and failure. This study defines a role of H3K23Pr in the context of cardiac health.