Branched chain amino acid metabolic reprogramming in heart failure

• Published in: Biochimica et biophysica acta Vol. 1862; no. 12; pp. 2270 - 2275
• Main Authors: Sun, Haipeng, Wang, Yibin
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-12-2016
• Subjects: Amino acid; Amino Acids, Branched-Chain - metabolism; Animals; BCAA; Carbohydrate Metabolism; Fatty Acids - metabolism; Heart failure; Heart Failure - metabolism; Heart Failure - pathology; Humans; Metabolism; Myocardium - metabolism; Myocardium - pathology; Remodeling; Heart failure; Amino acid; Metabolism; Remodeling; BCAA
• ISSN: 0925-4439; 0006-3002; 1879-260X
• DOI: 10.1016/j.bbadis.2016.09.009

Metabolic remodeling is a hall-mark of cardiac maturation and pathology. The switch of substrate utilization from glucose to fatty acid is observed during post-natal maturation period in developing heart, but the process is reversed from fatty acids to glucose in the failing hearts across different clinic and experimental models. Majority of the current investigations have been focusing on the regulatory mechanism and functional impact of this metabolic reprogramming involving fatty acids and carbohydrates. Recent progress in metabolomics and transcriptomic analysis, however, revealed another significant remodeled metabolic branch associated with cardiac development and disease, i.e. Branched-Chain Amino Acid (BCAA) catabolism. These findings have established BCAA catabolic deficiency as a novel metabolic feature in failing hearts with potentially significant impact on the progression of pathological remodeling and dysfunction. In this review, we will evaluate the current evidence and potential implication of these discoveries in the context of heart diseases and novel therapies.
This article is part of a Special Issue entitled: The role of post-translational protein modifications on heart and vascular metabolism edited by Jason R.B. Dyck & Jan F.C. Glatz.
•BCAA catabolic activity is dynamically regulated in cardiac development and diseases.•BCAA catabolic defects are associated with pathological remodeling and dysfunction.•Accumulation of BCAA and catabolic products may contribute to disease progression in the heart.•BCAA catabolic flux modulation is a potential therapeutic approach for heart failure.