Fueling fibrosis: BCAT1 links branched-chain amino acid metabolism to collagen production.

Abstract

Fibrosis remains a major driver of organ dysfunction, yet the metabolic programs that sustain extracellular matrix production are incompletely understood. In this issue of the JCI, Takizawa and colleagues identified branched-chain amino acid transaminase 1 (BCAT1) as a crucial metabolic regulator of fibroblast activation and fibrosis in a model of cardiac fibrosis. Their observations were corroborated by analyses of datasets from patients with heart failure with preserved ejection fraction and metabolic dysfunction-associated steatohepatitis. They report that by coupling mechanical and TGF-β signaling to a proline biosynthesis and utilization program, BCAT1 enhanced collagen production in activated cardiac fibroblasts. These findings place branched-chain amino acid metabolism as a pivotal contributor to fibroblast activation and highlight BCAT1 as a promising therapeutic target for fibrotic disease.