ACAD8 deficiency promotes pathological cardiac hypertrophy in response to pressure overload by regulating histone isobutyrylation
De-Pei Liu
Nature Communications, Published online: 11 May 2026; doi:10.1038/s41467-026-72949-w Valine metabolism disruption is linked to heart disease, but the mechanisms are unclear. Here, the authors show that ACAD8 deficiency drives isobutyryl-CoA accumulation and histone isobutyrylation, increasing chromatin accessibility and gene expression to promote cardiac hypertrophy, while ACAD8 overexpression reverses these effects.