Biography
Biography: Matthew E. Merritt
Abstract
The heart is an omnivorous organ, able to metabolize fattys acids (FAs), carbohydrates, and ketones to acetyl-CoA depending on their availability in the bloodstream. When the heart is subjected to overpressure due to stenosis or high blood pressure, it can hypertrophy and ultimately fail. This physical phenomena is intimately connected with a change in the substrate preference for the heart, where carbohydrate oxidation is emphasized over FA oxidation. Measuring substrate preference in the heart is tractable when nutrients positionally enriched in 13C can be supplied. Here we use a standard model of myocardial metabolism, the perfused mouse heart, to study substrate selection and the impact of providing propionate, an odd-chain fatty acid, on overall metabolism. We have found that propionate activates carbohydrate oxidation, leading to avid utilization of a hyperpolarized pyruvate tracer. Additonally, the propionate can cause a large change in pool sizes for the Krebs cycle intermediates without enforcing a change in flux as measured by O2 consumption. The propionate perfused heart should serve as an excellent model for validation of new isotopomer based methods for measuring metabolic flux.