Direct assessment of hepatic mitochondrial oxidative and anaplerotic fluxes in humans using dynamic 13C magnetic resonance spectroscopy
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Direct assessment of hepatic mitochondrial oxidative and anaplerotic fluxes in humans using dynamic 13C magnetic resonance spectroscopy. / 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.
In: Nature Medicine, Vol. 20, No. 1, 2014, p. 98-102.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Direct assessment of hepatic mitochondrial oxidative and anaplerotic fluxes in humans using dynamic 13C magnetic resonance spectroscopy
AU - Befroy, Douglas E
AU - Perry, Rachel J
AU - Jain, Nimit
AU - Dufour, Sylvie
AU - Cline, Gary W
AU - Trimmer, Jeff K
AU - Brosnan, Julia
AU - Rothman, Douglas L
AU - Petersen, Kitt Falk
AU - Shulman, Gerald I.
PY - 2014
Y1 - 2014
N2 - 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 (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.
AB - 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 (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.
KW - Carbon Radioisotopes
KW - Citric Acid Cycle
KW - Computer Simulation
KW - Diabetes Mellitus, Type 2
KW - Fatty Liver
KW - Humans
KW - Magnetic Resonance Spectroscopy
KW - Metabolic Networks and Pathways
KW - Mitochondria, Liver
KW - Monte Carlo Method
KW - Non-alcoholic Fatty Liver Disease
KW - Oxidation-Reduction
KW - Staining and Labeling
KW - Evaluation Studies
KW - Journal Article
KW - Research Support, N.I.H., Extramural
KW - Research Support, Non-U.S. Gov't
U2 - 10.1038/nm.3415
DO - 10.1038/nm.3415
M3 - Journal article
C2 - 24317120
VL - 20
SP - 98
EP - 102
JO - Nature Medicine
JF - Nature Medicine
SN - 1078-8956
IS - 1
ER -
ID: 174466361