TY - JOUR
T1 - Fatty liver disrupts glycerol metabolism in gluconeogenic and lipogenic pathways in humans
AU - Jin, Eunsook S.
AU - Browning, Jeffrey D.
AU - Murphy, Rebecca E.
AU - Malloy, Craig R.
N1 - Funding Information:
This study was supported by National Institutes of Health Grants DK099289 (E.S.J.), DK058398, and EB015908 (C.R.M.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Author’s Choice—Final version open access under the terms of the Creative Commons CC-BY license. Manuscript received 25 April 2018 and in revised form 27 July 2018. Published, JLR Papers in Press, July 27, 2018 DOI https://doi.org/10.1194/jlr.M086405
Publisher Copyright:
© 2018 American Society for Biochemistry and Molecular Biology Inc. All rights reserved.
PY - 2018
Y1 - 2018
N2 - It is a challenge to assess metabolic dysregulation in fatty liver of human patients prior to clinical manifestations. Here, we recruited obese, but otherwise healthy, subjects to examine biochemical processes in the liver with simple triglyceride accumulation using stable isotopes and NMR analysis of metabolic products in blood. Intrahepatic triglycerides were measured using 1 H magnetic resonance spectroscopy, and volunteers received 2 H 2 O and [U- 13 C 3 ] glycerol orally, followed by a series of blood draws. NMR analysis of plasma triglycerides and glucose provided detailed information about metabolic pathways in patients with simple hepatic steatosis. Compared with subjects with low hepatic fat, patients with hepatic steatosis were characterized by the following: lower 13 C enrichments in the glycerol backbones of triglycerides (i.e., TG-[ 13 C]glycerol), higher [U- 13 C 3 ] glycerol metabolism through the tricarboxylic acid (TCA) cycle, delayed gluconeogenesis from [U- 13 C 3 ]glycerol, and less flexibility in adjusting supporting fluxes of glucose production upon an oral load of glycerol. In summary, simple hepatic steatosis was associated with enhanced [U- 13 C 3 ] glycerol metabolism through pathways that intersect the TCA cycle and delayed gluconeogenesis from glycerol.
AB - It is a challenge to assess metabolic dysregulation in fatty liver of human patients prior to clinical manifestations. Here, we recruited obese, but otherwise healthy, subjects to examine biochemical processes in the liver with simple triglyceride accumulation using stable isotopes and NMR analysis of metabolic products in blood. Intrahepatic triglycerides were measured using 1 H magnetic resonance spectroscopy, and volunteers received 2 H 2 O and [U- 13 C 3 ] glycerol orally, followed by a series of blood draws. NMR analysis of plasma triglycerides and glucose provided detailed information about metabolic pathways in patients with simple hepatic steatosis. Compared with subjects with low hepatic fat, patients with hepatic steatosis were characterized by the following: lower 13 C enrichments in the glycerol backbones of triglycerides (i.e., TG-[ 13 C]glycerol), higher [U- 13 C 3 ] glycerol metabolism through the tricarboxylic acid (TCA) cycle, delayed gluconeogenesis from [U- 13 C 3 ]glycerol, and less flexibility in adjusting supporting fluxes of glucose production upon an oral load of glycerol. In summary, simple hepatic steatosis was associated with enhanced [U- 13 C 3 ] glycerol metabolism through pathways that intersect the TCA cycle and delayed gluconeogenesis from glycerol.
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U2 - 10.1194/jlr.M086405
DO - 10.1194/jlr.M086405
M3 - Article
C2 - 30054343
AN - SCOPUS:85052747591
SN - 0022-2275
VL - 59
SP - 1685
EP - 1694
JO - Journal of lipid research
JF - Journal of lipid research
IS - 9
ER -