Detection of Altered Hepatic Gluconeogenesis by Nuclear Magnetic Resonance (NMR) and Hyperpolarized 13C Pyruvate

Matthew E. Merritt¹, Crystal Harrison¹, Craig R. Malloy¹, A Dean Sherry¹, Shawn C. Burgess^1,2

Abnormal hepatic gluconeogenesis is a hallmark feature of obesity, insulin resistance and diabetes, but its measurement requires sophisticated tracer approaches and/or serial MRS measurements over several hours. We used the DNP process to hyperpolarize [1-13C]pyruvate and followed its incorporation into hepatic metabolites over 60 seconds by 13C NMR in isolated perfused mouse liver. In addition to lactate and alanine, several resonances consistent with mitochondrial intermediates of the TCA cycle were observed. The appearance of these metabolites was diminished in livers with impaired gluconeogenesis. The data demonstrate that HP-pyruvate will be useful to observe a number of hepatic pathways, including gluconeogenesis.