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Mechanism of Reduced Myocardial Glucose Utilization During Acute Hypertriglyceridemia in Rats

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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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Acknowledgements

A.C.C. was supported by a Junior 2 Scholarship from the Fonds de la recherche en santé du Québec (FRSQ). The Centre de recherche clinique Etienne-Le Bel is a FRSQ-funded research centre. This work was supported by grants from Association Diabète Québec, from the Heart and Stroke Foundation of Canada (the Jonathan-Ballon Award), and from the Canadian Institutes of Health Research (MOP 53094 and MOP 15348).

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Authors and Affiliations

  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

    Sébastien L. Ménard, Xiuli Ci, Frédérique Frisch, François Normand-Lauzière & André C. Carpentier

  2. Sherbrooke Molecular Imaging Center, Centre de Recherche Clinique Etienne-Le Bel, Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke, Sherbrooke, QC, Canada

    Jules Cadorette, René Ouellet, Johannes E. Van Lier, François Bénard, M’hamed Bentourkia & Roger Lecomte

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  1. Sébastien L. Ménard
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  11. André C. Carpentier
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Correspondence to André C. Carpentier.

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Ménard, S.L., Ci, X., Frisch, F. et al. Mechanism of Reduced Myocardial Glucose Utilization During Acute Hypertriglyceridemia in Rats. Mol Imaging Biol 11, 6–14 (2009). https://doi.org/10.1007/s11307-008-0171-2

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  • DOI: https://doi.org/10.1007/s11307-008-0171-2

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