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- Title
Direct assessment of hepatic mitochondrial oxidative and anaplerotic fluxes in humans using dynamic <sup>13</sup>C magnetic resonance spectroscopy.
- Authors
Befroy, Douglas E; Perry, Rachel J; Jain, Nimit; Dufour, Sylvie; Cline, Gary W; Trimmer, Jeff K; Brosnan, Julia; Rothman, Douglas L; Petersen, Kitt Falk; Shulman, Gerald I
- 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 13C-labeling strategy in combination with 13C 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 (VTCA) and anaplerotic flux (VANA) 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 VANA/VTCA 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.
- Publication
Nature Medicine, 2014, Vol 20, Issue 1, p98
- ISSN
1078-8956
- Publication type
Academic Journal
- DOI
10.1038/nm.3415