High Serum Branched-Chain Amino Acids Level Independently Predicts Incident Heart Failure—The Hong Kong Diabetes Register

Background: Cardiac cachexia (CC) adversely affects the lifestyle of heart failure (HF) patients. The current study examined the impact of melatonin cosupplementation and branched-chain amino acids (BCAAs) on quality of life (QoL), fatigue, and nutritional status in cachectic HF patients. Methods: In this trial, 84 CC patients were randomized to melatonin, BCAAs, or coadministration (both) as intervention groups and a control group over 8 weeks. At baseline and postintervention, QoL, fatigue, and nutritional status were assessed. Results: After intervention, improvement in the overall and physical dimensions of QoL and appetite score were found to be statistically significant in the BCAAs (P < .001) and the melatonin+BCAAs (P < .001) groups compared with the placebo group. The emotional dimension score was significantly lower in the BCAAs group compared with the placebo group (P = .001). There was a statistically significant improvement in fatigue severity in all 3 intervention groups compared with the placebo group. The nutrition risk index (NRI) score increased significantly only in the melatonin group (P = .015), and there was no significant difference between the other groups (P = .804). Conclusions: Cosupplementation with BCAAs and melatonin improved QoL, fatigue status, and appetite in cachectic HF patients but did not affect NRI.

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Abstract 86: Catabolic Remodeling of Branched Chain Amino Acids in Heart Failure

Circulation Research ◽

10.1161/res.111.suppl_1.a86 ◽

2012 ◽

Vol 111 (suppl_1) ◽

Author(s):

Haipeng Sun ◽

Meiyi Zhou ◽

Chen Gao ◽

Kristine Olson ◽

Ji-Youn Youn ◽

...

Keyword(s):

Heart Failure ◽

Amino Acids ◽

Regulatory Protein ◽

Pressure Overload ◽

Branched Chain Amino Acids ◽

Atp Production ◽

Genetic Ablation ◽

Catabolic Genes ◽

Metabolic Remodeling ◽

Branched Chain

Metabolic remodeling is an integral part of heart failure. Although glucose and fatty acids metabolism have been extensively studied, little is known about the role of amino acids homeostasis in heart physiology and pathology. Branched chain amino acids (BCAAs), including leucine, isoleucine, and valine, are essential amino acids for both protein synthesis and cellular signaling. Elevated levels of BCAAs have been linked with heart failure. However, the underlying regulatory mechanism and functional significance of abnormal BCAA catabolism in heart failure have not been established. We found that genes involved in BCAA catabolism, including a key regulatory protein PP2Cm, are significantly down-regulated at mRNA as well as protein level in pressure-overload induced failing heart in mice. Furthermore, the concentrations of BCAA catabolic products branched-chain keto acids (BCKAs) are also elevated in heart tissues of post TAC mice. Interestingly, the down-regulation of BCAA catabolic genes mimics a similar expression pattern observed in fetal heart, suggesting that decreased BCAA catabolic activity is part of the metabolic remodeling in pathologically stressed heart from an adult to a fetal-like state. Genetic ablation of PP2Cm in mouse leads to defect in BCAA catabolism and accumulation of BCAAs and BCKAs in cardiac tissue and serum. PP2Cm deficient mice had lower cardiac contractility and higher susceptibility to develop heart failure under pressure overload. In addition, BCKAs treatment to isolated mitochondria resulted in lower oxygen consumption rate and ATP production. PP2Cm deficiency as well as BCKAs treatment induced oxidative stress in cardiomyocyte and antioxidant treatment ameliorated the development of heart failure in PP2Cm deficient animals. Together, these data indicated that BCAA catabolic remodeling is likely an integrated component of metabolic remodeling during heart failure. More importantly, mis-regulation of BCAA catabolism in heart promoted heart failure progression, involving direct impact on mitochondrial function and redox homeostasis in cardiomyocytes.

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