Literature DB >> 24317120

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

Douglas E Befroy1, Rachel J Perry2, Nimit Jain3, Sylvie Dufour4, Gary W Cline5, Jeff K Trimmer6, Julia Brosnan6, Douglas L Rothman7, Kitt Falk Petersen8, Gerald I Shulman9.   

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.

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Year:  2013        PMID: 24317120      PMCID: PMC3947269          DOI: 10.1038/nm.3415

Source DB:  PubMed          Journal:  Nat Med        ISSN: 1078-8956            Impact factor:   53.440


  33 in total

1.  Astroglial contribution to brain energy metabolism in humans revealed by 13C nuclear magnetic resonance spectroscopy: elucidation of the dominant pathway for neurotransmitter glutamate repletion and measurement of astrocytic oxidative metabolism.

Authors:  Vincent Lebon; Kitt F Petersen; Gary W Cline; Jun Shen; Graeme F Mason; Sylvie Dufour; Kevin L Behar; Gerald I Shulman; Douglas L Rothman
Journal:  J Neurosci       Date:  2002-03-01       Impact factor: 6.167

2.  Quantitation of muscle glycogen synthesis in normal subjects and subjects with non-insulin-dependent diabetes by 13C nuclear magnetic resonance spectroscopy.

Authors:  G I Shulman; D L Rothman; T Jue; P Stein; R A DeFronzo; R G Shulman
Journal:  N Engl J Med       Date:  1990-01-25       Impact factor: 91.245

3.  Resistance to thyroid hormone is associated with raised energy expenditure, muscle mitochondrial uncoupling, and hyperphagia.

Authors:  Catherine S Mitchell; David B Savage; Sylvie Dufour; Nadia Schoenmakers; Peter Murgatroyd; Douglas Befroy; David Halsall; Samantha Northcott; Philippa Raymond-Barker; Suzanne Curran; Elana Henning; Julia Keogh; Penny Owen; John Lazarus; Douglas L Rothman; I Sadaf Farooqi; Gerald I Shulman; Krishna Chatterjee; Kitt Falk Petersen
Journal:  J Clin Invest       Date:  2010-03-08       Impact factor: 14.808

4.  Excessive hepatic mitochondrial TCA cycle and gluconeogenesis in humans with nonalcoholic fatty liver disease.

Authors:  Nishanth E Sunny; Elizabeth J Parks; Jeffrey D Browning; Shawn C Burgess
Journal:  Cell Metab       Date:  2011-12-07       Impact factor: 27.287

5.  Effect of triiodothyronine on mitochondrial energy coupling in human skeletal muscle.

Authors:  V Lebon; S Dufour; K F Petersen; J Ren; B M Jucker; L A Slezak; G W Cline; D L Rothman; G I Shulman
Journal:  J Clin Invest       Date:  2001-09       Impact factor: 14.808

6.  Zonation of acetate labeling across the liver: implications for studies of lipogenesis by MIDA.

Authors:  M A Puchowicz; I R Bederman; B Comte; D Yang; F David; E Stone; K Jabbour; D H Wasserman; H Brunengraber
Journal:  Am J Physiol       Date:  1999-12

7.  Clinical NOE 13C MRS for neuropsychiatric disorders of the frontal lobe.

Authors:  Napapon Sailasuta; Larry W Robertson; Kent C Harris; Andrea L Gropman; Peter S Allen; Brian D Ross
Journal:  J Magn Reson       Date:  2008-09-17       Impact factor: 2.229

8.  Glucose production, gluconeogenesis, and hepatic tricarboxylic acid cycle fluxes measured by nuclear magnetic resonance analysis of a single glucose derivative.

Authors:  Eunsook S Jin; John G Jones; Matthew Merritt; Shawn C Burgess; Craig R Malloy; A Dean Sherry
Journal:  Anal Biochem       Date:  2004-04-15       Impact factor: 3.365

9.  Abnormal hepatic energy homeostasis in type 2 diabetes.

Authors:  Julia Szendroedi; Marek Chmelik; Albrecht Ingo Schmid; Peter Nowotny; Attila Brehm; Martin Krssak; Ewald Moser; Michael Roden
Journal:  Hepatology       Date:  2009-10       Impact factor: 17.425

10.  Simultaneous determination of the rates of the TCA cycle, glucose utilization, alpha-ketoglutarate/glutamate exchange, and glutamine synthesis in human brain by NMR.

Authors:  G F Mason; R Gruetter; D L Rothman; K L Behar; R G Shulman; E J Novotny
Journal:  J Cereb Blood Flow Metab       Date:  1995-01       Impact factor: 6.200

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  42 in total

1.  High-sensitivity, broadband-decoupled (13) C MR spectroscopy in humans at 7T using two-dimensional heteronuclear single-quantum coherence.

Authors:  Robin A de Graaf; Henk M De Feyter; Douglas L Rothman
Journal:  Magn Reson Med       Date:  2014-09-29       Impact factor: 4.668

2.  Effects of Deuteration of 13C-Enriched Phospholactate on Efficiency of Parahydrogen-Induced Polarization by Magnetic Field Cycling.

Authors:  Oleg G Salnikov; Roman V Shchepin; Nikita V Chukanov; Lamya Jaigirdar; Wellington Pham; Kirill V Kovtunov; Igor V Koptyug; Eduard Y Chekmenev
Journal:  J Phys Chem C Nanomater Interfaces       Date:  2018-10-02       Impact factor: 4.126

3.  Ketogenesis prevents diet-induced fatty liver injury and hyperglycemia.

Authors:  David G Cotter; Baris Ercal; Xiaojing Huang; Jamison M Leid; D André d'Avignon; Mark J Graham; Dennis J Dietzen; Elizabeth M Brunt; Gary J Patti; Peter A Crawford
Journal:  J Clin Invest       Date:  2014-10-27       Impact factor: 14.808

Review 4.  Multiorgan, Multimodality Imaging in Cardiometabolic Disease.

Authors:  Vidhya Kumar; Willa A Hsueh; Subha V Raman
Journal:  Circ Cardiovasc Imaging       Date:  2017-11       Impact factor: 7.792

Review 5.  Stable isotope-based flux studies in nonalcoholic fatty liver disease.

Authors:  Arthur McCullough; Stephen Previs; Takhar Kasumov
Journal:  Pharmacol Ther       Date:  2017-07-16       Impact factor: 12.310

6.  Determination of Fatty Acid Oxidation and Lipogenesis in Mouse Primary Hepatocytes.

Authors:  Thomas E Akie; Marcus P Cooper
Journal:  J Vis Exp       Date:  2015-08-27       Impact factor: 1.355

7.  (13)C MRS of human brain at 7 Tesla using [2-(13)C]glucose infusion and low power broadband stochastic proton decoupling.

Authors:  Shizhe Li; Li An; Shao Yu; Maria Ferraris Araneta; Christopher S Johnson; Shumin Wang; Jun Shen
Journal:  Magn Reson Med       Date:  2015-04-27       Impact factor: 4.668

8.  Mitochondrial metabolism mediates oxidative stress and inflammation in fatty liver.

Authors:  Santhosh Satapati; Blanka Kucejova; Joao A G Duarte; Justin A Fletcher; Lacy Reynolds; Nishanth E Sunny; Tianteng He; L Arya Nair; Kenneth A Livingston; Kenneth Livingston; Xiaorong Fu; Matthew E Merritt; A Dean Sherry; Craig R Malloy; John M Shelton; Jennifer Lambert; Elizabeth J Parks; Ian Corbin; Mark A Magnuson; Jeffrey D Browning; Shawn C Burgess
Journal:  J Clin Invest       Date:  2015-11-16       Impact factor: 14.808

9.  In Vivo Estimates of Liver Metabolic Flux Assessed by 13C-Propionate and 13C-Lactate Are Impacted by Tracer Recycling and Equilibrium Assumptions.

Authors:  Clinton M Hasenour; Mohsin Rahim; Jamey D Young
Journal:  Cell Rep       Date:  2020-08-04       Impact factor: 9.423

10.  Hepatic mTORC1 Opposes Impaired Insulin Action to Control Mitochondrial Metabolism in Obesity.

Authors:  Blanka Kucejova; Joao Duarte; Santhosh Satapati; Xiaorong Fu; Olga Ilkayeva; Christopher B Newgard; James Brugarolas; Shawn C Burgess
Journal:  Cell Rep       Date:  2016-06-23       Impact factor: 9.423

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