Mechanism of reduced myocardial glucose utilization during acute hypertriglyceridemia in rats

Mol Imaging Biol. 2009 Jan-Feb;11(1):6-14. doi: 10.1007/s11307-008-0171-2. Epub 2008 Sep 4.

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 [(3)H]-triolein and [(14)C]-bromopalmitate, respectively. Myocardial blood flow, oxidative metabolism, and metabolic rate of glucose (MMRG) were determined using micro-positron emission tomography (microPET) with [(13)N]-ammonia, [(11)C]-acetate, and 2-deoxy-2-[F-18]fluoro-D: -glucose (FDG).

Results: TRI reduced myocardial incorporation of [(3)H]-triolein but not [(14)C]-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / metabolism
  • Acute Disease
  • Ammonia / metabolism
  • Animals
  • Detergents / pharmacology
  • Fat Emulsions, Intravenous / metabolism
  • Fatty Acids / metabolism
  • Fatty Acids, Nonesterified / blood
  • Fatty Acids, Nonesterified / metabolism
  • Fluorodeoxyglucose F18 / metabolism
  • Glucose / metabolism*
  • Glucose Clamp Technique
  • Hypertriglyceridemia / diagnostic imaging
  • Hypertriglyceridemia / metabolism*
  • Lipolysis
  • Male
  • Models, Biological
  • Myocardium / metabolism*
  • Polyethylene Glycols / pharmacology
  • Positron-Emission Tomography
  • Radiopharmaceuticals / metabolism
  • Rats
  • Rats, Wistar
  • Triglycerides / blood
  • Triglycerides / metabolism
  • Triolein / metabolism

Substances

  • Acetates
  • Detergents
  • Fat Emulsions, Intravenous
  • Fatty Acids
  • Fatty Acids, Nonesterified
  • Radiopharmaceuticals
  • Triglycerides
  • Fluorodeoxyglucose F18
  • Triolein
  • Polyethylene Glycols
  • Ammonia
  • Glucose
  • tyloxapol