Isotopic measurement of muscle triglyceride synthesis and breakdown rates

Abstract

Whereas intracellular lipid disregulation is linked to insulin resistance, quantitative measurement of lipid metabolism in the muscle has not been adequately described. We developed a stable isotopic method to quantify muscle triglyceride (TG) kinetics. L‐[U‐13C16]palmitate was injected as a bolus in 4 anesthetized rabbits; arterial blood and muscle samples were taken before the injection and at 2, 5 and 10 min after the injection. Muscle TG and phospholipid (PL) fractional synthesis rate (FSR) was measured using the tracer incorporation method and its fractional breakdown rate (FBR) was measured using the tracee release method. The absolute synthesis or breakdown rate was calculated by FSR (or FBR) x pool size. Intramyocellular palmitoyl‐coenzyme A was used as the precursor for lipid synthesis. In the postabsorptive state muscle TG FSR was 0.10 ± 0.02%/h (6.81 ± 1.50 nmol/g.h), FBR was 0.30 ± 0.07 %/h (20.07 ± 4.68 nmol/g.h). Thus, there was a net TG loss of 0.20 ± 0.05 %/h (13.20 ± 3.32 nmol/g.h). Muscle PL FSR was 0.91 ± 0.06 %/h (20.42 ± 1.35 nmol/g.h), greater (p<0.01) than the corresponding values of muscle TG synthesis. This method measures both the synthesis and breakdown rates of muscle TG as well as muscle lipids pool sizes, and could be a useful tool in studying the metabolic mechanism of peripheral insulin resistance. Supported by Shriners grants 8560, 8600 and 8490.