Mechanism of Reduced Myocardial Glucose Utilization During Acute Hypertriglyceridemia in Rats |
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Authors: | Sébastien L Ménard Xiuli Ci Frédérique Frisch François Normand-Lauzière Jules Cadorette René Ouellet Johannes E Van Lier François Bénard M’hamed Bentourkia Roger Lecomte André C Carpentier |
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Institution: | (1) Department of Medicine, Division of Endocrinology, Centre de Recherche Clinique Etienne-Le Bel, Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke, 3001, 12th Ave. North, Sherbrooke, QC, Canada, J1H 5H4;(2) Sherbrooke Molecular Imaging Center, Centre de Recherche Clinique Etienne-Le Bel, Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke, Sherbrooke, QC, Canada |
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Abstract: | Purpose The purpose of the research is to study the effect of acute inhibition of intravascular lipolysis on myocardial substrate
selection during hypertriglyceridemia using in vivo radiotracer analysis and positron emission tomography.
Procedures We induced acute hypertriglyceridemia in vivo using an intravenous infusion of Intralipid 20% (IL) without and with acute inhibition of fatty acid delivery from circulating
triglycerides with injection of Triton WR-1339 (TRI) during a euglycemic–hyperinsulinemic clamp in Wistar rats. We determined
the effect of TRI on myocardial uptake of circulating triglycerides and free fatty acids using intravenous injection of 3H]-triolein and 14C]-bromopalmitate, respectively. Myocardial blood flow, oxidative metabolism, and metabolic rate of glucose (MMRG) were determined
using micro-positron emission tomography (μPET) with 13N]-ammonia, 11C]-acetate, and 2-deoxy-2-F-18]fluoro-d-glucose (FDG).
Results TRI reduced myocardial incorporation of 3H]-triolein but not 14C]-bromopalmitate showing that it selectively reduces myocardial fatty acid delivery from circulating triglycerides but not
from free fatty acids. IL reduced myocardial blood flow and MMRG by 37% and 56%, respectively, but did not affect myocardial
oxidative metabolism. TRI did not abolish the effect of IL on myocardial blood flow and MMRG.
Conclusions Hypertriglyceridemia acutely reduces myocardial blood flow and MMRG in rats, but this effect is not explained by increased
myocardial fatty acid delivery through intravascular triglyceride lipolysis. |
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Keywords: | Intravascular lipolysis Triglyceride-rich lipoproteins Fatty acid metabolism Myocardial metabolism Lipoprotein lipase Triton WR-1339 FDG |
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