Non-invasive assessment of hepatic mitochondrial metabolism by positional isotopomer NMR tracer analysis (PINTA)

Rachel J. Perry, Liang Peng, Gary W. Cline, Gina M. Butrico, Yongliang Wang, Xian-Man Zhang, Douglas L. Rothman, Kitt Falk Petersen and Gerald I. Shulman ()
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Rachel J. Perry: Yale University School of Medicine
Liang Peng: Yale University School of Medicine
Gary W. Cline: Yale University School of Medicine
Gina M. Butrico: Yale University School of Medicine
Yongliang Wang: Yale University School of Medicine
Xian-Man Zhang: Yale University School of Medicine
Douglas L. Rothman: Yale University School of Medicine
Kitt Falk Petersen: Yale University School of Medicine
Gerald I. Shulman: Yale University School of Medicine

Nature Communications, 2017, vol. 8, issue 1, 1-9

Abstract: Abstract Hepatic mitochondria play a central role in the regulation of intermediary metabolism and maintenance of normoglycemia, and there is great interest in assessing rates of hepatic mitochondrial citrate synthase flux (VCS) and pyruvate carboxylase flux (VPC) in vivo. Here, we show that a positional isotopomer NMR tracer analysis (PINTA) method can be used to non-invasively assess rates of VCS and VPC fluxes using a combined NMR/gas chromatography-mass spectrometry analysis of plasma following infusion of [3-13C]lactate and glucose tracer. PINTA measures VCS and VPC fluxes over a wide range of physiological conditions with minimal pyruvate cycling and detects increased hepatic VCS following treatment with a liver-targeted mitochondrial uncoupler. Finally, validation studies in humans demonstrate that the VPC/VCS ratio measured by PINTA is similar to that determined by in vivo NMR spectroscopy. This method will provide investigators with a relatively simple tool to non-invasively examine the role of altered hepatic mitochondrial metabolism.

Date: 2017
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DOI: 10.1038/s41467-017-01143-w

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