Assessment of Hepatic Mitochondrial Oxidation and Pyruvate Cycling in NAFLD by (13)C Magnetic Resonance Spectroscopy

TY - JOUR

T1 - Assessment of Hepatic Mitochondrial Oxidation and Pyruvate Cycling in NAFLD by (13)C Magnetic Resonance Spectroscopy

AU - Petersen, Kitt Mia Falck

AU - Befroy, Douglas E

AU - Dufour, Sylvie

AU - Rothman, Douglas L

AU - Shulman, Gerald I.

N1 - Copyright © 2016 Elsevier Inc. All rights reserved.

PY - 2016/7/12

Y1 - 2016/7/12

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1016/j.cmet.2016.06.005

DO - 10.1016/j.cmet.2016.06.005

M3 - Journal article

C2 - 27411016

SN - 1550-4131

VL - 24

SP - 167

EP - 171

JO - Cell Metabolism

JF - Cell Metabolism

IS - 1

ER -