Direct assessment of hepatic mitochondrial oxidative and anaplerotic fluxes in humans using dynamic (13)C magnetic resonance spectroscopy

Despite the central role of the liver in the regulation of glucose and lipid metabolism there are currently no methods to directly assess hepatic oxidative metabolism in humans in vivo. By utilizing a novel (13)C-labeling strategy in combination with (13)C magnetic resonance spectroscopy we show that rates of mitochondrial oxidation and anaplerosis in human liver can be directly determined noninvasively. Using this approach we found the mean rates of hepatic TCA cycle flux (V(TCA)) and anaplerotic flux (V(ANA)) to be 0.43 ± 0.04 μmol (g-liver-min)(−1) and 0.60 ± 0.11 μmol (g-liver-min)(−1), respectively, in fourteen healthy, lean, individuals. We also found the ratio V(ANA)/V(TCA) to be 1.39 ± 0.22, which is several fold lower than recently published estimates using an indirect approach. This method will be useful for understanding the pathogenesis of non-alcoholic fatty liver disease and type 2 diabetes as well as assessing the effectiveness of new therapies targeting these pathways in man.