White-McGarrah lab identifies new connection between branched-chain amino acids and heart health

A team of researchers led by DMPI faculty members, Robert McGarrah and Phillip White of the White-McGarrah lab, have identified a novel pathophysiologic effect for a class of branched-chain amino acid (BCAA) metabolites called branched-chain keto acids (BCKA) in the heart. In an array of experiments conducted by Jackie Walejko, Bridgette Christopher, Scott Crown, and Guofang Zhang the team demonstrated that acute exposure of the heart to levels of BCKA found in obese but not lean individuals rapidly alters the phosphoproteomic landscape of the heart and activates cardiac protein synthesis. The team also employed stable-isotope resolved metabolomics to map the metabolic fate of BCKA in the heart and demonstrate that the newly identified mitochondrial BCAA carrier is a major determinant of cardiac BCAA metabolism. The manuscript describing these findings is published in the journal Nature Communications. Dr Jackie Walejko, (pictured right), the co-first author of this work was one of two recipients nationally to be awarded a highly competitive Cardiovascular-Metabolic fellowships from the American Diabetes Association in December of 2020 and will use this funding to explore the role of chronically elevated BCKA on heart health in rodent models of diabetes over the next two years. The team hopes that insight gained from these studies will open new avenues to reduce cardiovascular disease burden in individuals with diabetes.

Congratulations Jackie!