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Elevations in circulating levels of branched-chain amino acids (BCAA) are associated with a variety of cardiometabolic diseases and conditions. Restriction of dietary BCAA in rodent models of obesity lowers circulating BCAA levels and improves whole animal and skeletal muscle insulin sensitivity and lipid homeostasis, but the impact of BCAA supply on heart metabolism has not been studied. Here we report that feeding a BCAA-restricted chow diet to Zucker fatty rats (ZFR) causes a shift in cardiac fuel metabolism that favors fatty acid relative to glucose catabolism. This is illustrated by an increase in labeling of acetyl CoA from [1-C]palmitate and a decrease in labeling of acetyl-CoA and malonyl-CoA from [U-C]glucose, accompanied by a decrease in cardiac hexokinase II and GLUT4 protein levels. Metabolomic profiling of heart tissue supports these findings by demonstrating an increase in levels of a host of fatty acid-derived metabolites in hearts from ZFR and Zucker lean rats (ZLR) fed the BCAA-restricted diet. In addition, the two-fold increase in cardiac triglyceride stores in ZFR compared to ZLR fed on chow diet is eliminated in ZFR fed on the BCAA-restricted diet. Finally, the enzymatic activity of branched chain ketoacid dehydrogenase (BCKDH) is not influenced by BCAA restriction, and levels of BCAA in heart instead reflect their levels in circulation. In summary, reducing BCAA supply in obesity improves cardiac metabolic health by a mechanism independent of alterations in BCKDH activity.
This article was published in the following journal.
Name: American journal of physiology. Endocrinology and metabolism
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An autosomal recessive disorder of fatty acid oxidation, and branched chain amino acids (AMINO ACIDS, BRANCHED-CHAIN); LYSINE; and CHOLINE catabolism, that is due to defects in either subunit of ELECTRON TRANSFER FLAVOPROTEIN or its dehydrogenase, electron transfer flavoprotein-ubiquinone oxidoreductase (EC 220.127.116.11).
Amino acids which have a branched carbon chain.
An essential branched-chain amino acid important for hemoglobin formation.
A branched-chain essential amino acid that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway.
An essential branched-chain aliphatic amino acid found in many proteins. It is an isomer of LEUCINE. It is important in hemoglobin synthesis and regulation of blood sugar and energy levels.
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