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Nat Med. 2014 Jan;20(1):98-102. doi: 10.1038/nm.3415. Epub 2013 Dec 8.

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

Author information

  • 11] Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut, USA. [2] Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA. [3].
  • 21] Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA. [2] Department of Cellular & Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut, USA. [3].
  • 3Department of Biomedical Engineering, Yale University School of Medicine, New Haven, Connecticut, USA.
  • 4Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut, USA.
  • 5Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
  • 6Pfizer Pharmaceuticals, Groton, Connecticut, USA.
  • 71] Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut, USA. [2] Department of Biomedical Engineering, Yale University School of Medicine, New Haven, Connecticut, USA.
  • 81] Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA. [2] Novo Nordisk Foundation Center for Basic Metabolic Research, Copenhagen, Denmark.
  • 91] Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA. [2] Department of Cellular & Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut, USA. [3] Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut, USA. [4] Novo Nordisk Foundation Center for Basic Metabolic Research, Copenhagen, Denmark.

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 (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.

PMID:
24317120
[PubMed - indexed for MEDLINE]
PMCID:
PMC3947269
Free PMC Article
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