title: Assessment of Hepatic Mitochondrial Oxidation and Pyruvate Cycling in NAFLD by (13)C Magnetic Resonance Spectroscopy.
abstract: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and there is great interest in understanding the potential role of alterations in mitochondrial metabolism in its pathogenesis. To address this question, we assessed rates of hepatic mitochondrial oxidation in subjects with and without NAFLD by monitoring the rate of (13)C labeling in hepatic [5-(13)C]glutamate and [1-(13)C]glutamate by (13)C MRS during an infusion of [1-(13)C]acetate. We found that rates of hepatic mitochondrial oxidation were similar between NAFLD and control subjects. We also assessed rates of hepatic pyruvate cycling during an infusion of [3-(13)C]lactate by monitoring the (13)C label in hepatic [2-(13)C]alanine and [2-(13)C]glutamate and found that this flux was also similar between groups and more than 10-fold lower than previously reported. Contrary to previous studies, we show that hepatic mitochondrial oxidation and pyruvate cycling are not altered in NAFLD and do not account for the hepatic fat accumulation.
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510, USA; The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen DK-2200, Denmark. Electronic address: kitt.petersen@yale.edu.
authors.forename: Kitt Falk
authors.initials: KF
authors.lastname: Petersen
authors.affiliation: Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Befroy
authors.affiliation: Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Dufour
authors.affiliation: Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT 06510, USA; Department of Biomedical Engineering, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Rothman
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510, USA; Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06510, USA; Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA; The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen DK-2200, Denmark. Electronic address: gerald.shulman@yale.edu.
authors.forename: Gerald I
authors.initials: GI
authors.lastname: Shulman
mesh_terms: D000328:Adult; D000886:Anthropometry; D002244:Carbon / Q000378:metabolism; D066241:Carbon-13 Magnetic Resonance Spectroscopy / Q000379:methods*; D016022:Case-Control Studies; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism*; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism*; D010084:Oxidation-Reduction; D019289:Pyruvic Acid / Q000378:metabolism*; D013997:Time Factors
chemical_list: D018698:Glutamic Acid; D002244:Carbon; D019289:Pyruvic Acid