Douglas E. Befroy1,2, Kitt Falk Petersen2, Peter B. Brown1, Douglas L. Rothman1,3, Gerald I. Shulman2,4
1Diagnostic Radiology, Yale University School of Medicine, New Haven, CT, United States; 2Internal Medicine, Yale University School of Medicine, New Haven, CT, United States; 3Biomedical Engineering, Yale University School of Medicine, New Haven, CT, United States; 4Howard Hughes Medical Institute, New Haven, CT, United States
Monitoring liver TCA cycle metabolism in vivo using classic 13C labeling strategies (infusing 1-13C glucose or 2-13C acetate) is unfeasible since intrahepatic lipid obscures the detection of C4-glutamate enrichment. Recently, alternative labeling schemes have been demonstrated in brain whereby enrichment at C5-glutamate, which resonates in a region free from overlapping lipid peaks, was monitored following the infusion of 2-13C glucose or 1-13C acetate. By adopting this strategy, we established that C5-glutamate enrichment can be detected in human liver without interference from intracellular lipid and observed hepatic substrate oxidation via the TCA cycle for the first time.