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

Abstract

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 using a new 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 tricarboxylic acid (TCA) cycle flux (V TCA) and anaplerotic flux (V ANA) to be 0.43 ± 0.04 μmol g -1 min -1 and 0.60 ± 0.11 μmol g -1 min -1, respectively, in twelve healthy, lean individuals. We also found the V ANA /V TCA ratio to be 1.39 ± 0.22, which is severalfold lower than recently published estimates using an indirect approach. This method will be useful for understanding the pathogenesis of nonalcoholic fatty liver disease and type 2 diabetes, as well as for assessing the effectiveness of new therapies targeting these pathways in humans.