Journal
NATURE MEDICINE
Volume 20, Issue 1, Pages 98-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.3415
Keywords
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Funding
- US Public Health Service [R24 DK-085638, R01 AG-23686, R01 DK-49230, P30 DK-45735, UL1 RR-024139]
- American Diabetes Association
- Pfizer
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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 C-13-labeling strategy in combination with C-13 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 mu mol g(-1) min(-1) and 0.60 +/- 0.11 mu mol 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.
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