The Fate of Hyperpolarized [1-13C]Pyruvate During Substrate Competition Reveals Increased Bicarbonate as a Potential Biomarker for Decreased Fatty Acid Oxidation

Karlos X. Moreno¹, A. Dean Sherry¹, Craig R. Malloy¹, Matthew E. Merritt¹

The effect of hepatic substrate utilization on hyperpolarized (HP) pyruvate metabolism was examined in isolated mouse livers. Livers were perfused with four different solutions varying in pyruvate, lactate and octanoate content, to potentially modulate hepatic pyruvate metabolism. After perfusion to steady-state with (10:1) lactate:pyruvate, a 3-fold increase in bicarbonate intensity was observed, compared to other solutions, upon administration of 4 mM HP-pyruvate. Carbon-13 isotopomer analysis of liver extracts confirms the increase was due to increased PDH flux. The remaining octanoate-containing solutions had no effect on bicarbonate intensity. These results reflect a possible biomarker for identification of deficient fatty acid oxidation.