Catabolic Defect of Branched-Chain Amino Acids Promotes Heart Failure.

ABSTRACT:

Background

Although metabolic reprogramming is critical in the pathogenesis of heart failure, studies to date have focused principally on fatty acid and glucose metabolism. Contribution of amino acid metabolic regulation in the disease remains understudied.

Methods and results

Transcriptomic and metabolomic analyses were performed in mouse failing heart induced by pressure overload. Suppression of branched-chain amino acid (BCAA) catabolic gene expression along with concomitant tissue accumulation of branched-chain α-keto acids was identified as a significant signature of metabolic reprogramming in mouse failing hearts and validated to be shared in human cardiomyopathy hearts. Molecular and genetic evidence identified the transcription factor Krüppel-like factor 15 as a key

SUBMITTER: Sun H 

PROVIDER: S-EPMC4879058 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature