Abstract
Objective
A three-day high-fat diet induces hepatic steatosis and hepatic insulin resistance
in rats without altering fasting plasma glucose concentration or the rate of glucose
production. However, as the nutrient profile available to the liver is substantially
altered by a high-fat diet, we hypothesized that the relative fluxes supporting hepatic
glucose production would be altered.
Materials/Methods
To test this hypothesis, we used multiple tracers ([3,4-13C2]glucose, 2H2O, and [U-13C3]propionate) followed by NMR analysis of blood glucose to quantify net glucose production
and the contributions of glycogen and key gluconeogenesis precursors in 4–5-h fasted
rats.
Results
NMR analysis demonstrated that the majority of blood glucose was derived from glycogen
and the citric acid cycle, while a smaller fraction of glucose was derived from glycerol
in both controls and high-fat-fed animals. High-fat feeding was associated with a
two-fold increase in plasma glycerol concentration and an increase in the contribution
(both fractional and absolute) of glycerol-gluconeogenesis. The increase in gluconeogenesis
from glycerol tended to be balanced by a decrease in glycogenolysis. The absolute
fluxes associated with the citric acid cycle including gluconeogenesis from the cycle
intermediates, pyruvate cycling and the citric acid cycle flux itself, were not altered
by this short high-fat diet.
Conclusions
A short term high-fat diet altered the specific pathways for hepatic glucose production
without influencing the overall rate of glucose production or flux in the citric acid
cycle.
Abbreviations:
CS (citrate synthase), DHAP (dihydroxyacetone phosphate), EGP (endogenous glucose production), FBP (fructose 1,6-bisphosphate), FUM (fumarate), F6P (fructose 6-phosphate), GA3P (glyceraldehyde 3-phosphate), GNG (gluconeogenesis), G6P (glucose 6-phosphate), G6Pase (Glucose 6-phosphatase), HFD (high-fat diet), MAG (monoacetone glucose), MAL (malate), ME (malic enzyme), NEFAs (non-esterified fatty acids), NMR (nuclear magnetic resonance), OAA (oxaloacetate), PCR (polymerase chain reaction), PEP (phosphoenolpyruvate), PEPCK (phosphoenolpyruvate carboxykinase), PK (pyruvate kinase), PKC (protein kinase C), ppm (parts/million), PPP (pentose phosphate pathway), SUCC (succinyl-CoA)Keywords
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Article info
Publication history
Published online: September 14, 2012
Accepted:
July 17,
2012
Received:
May 15,
2012
Identification
Copyright
© 2013 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
