Douglas E. Befroy1,
2, Nimit Jain3, Kitt Falk Petesen2, Gerald I.
Shulman2, 4, Douglas L. Rothman3, 5
1Diagnostic
Radiology, Yale University, New Haven, CT, United States; 2Internal
Medicine, Yale School of Medicine, New Haven, CT, United States; 3Diagnostic
Radiology, Yale School of Medicine, New Haven, CT, United States; 4Howard
Hughes Medical Institute, Yale School of Medicine, New Haven, CT, United
States; 5Biomedical Engineering, Yale University, New Haven, CT,
United States
We have previously demonstrated that oxidative metabolism can be observed in human liver in vivo using 13C-MRS in conjunction with a novel 13C-labeling strategy. In this study we describe the implementation of this methodology to determine rates of hepatic TCA cycle flux and anaplerosis in healthy individuals. To accurately simulate the kinetics of 13C-label turnover and generate robust estimates of these fluxes we also developed a model of hepatic metabolism that includes phenomena which distinguish the liver from other tissues. These studies provide the first direct estimates of liver TCA cycle flux and anaplerosis in vivo.