The tissue distribution of lipoprotein lipase determines where chylomicrons bind

Abstract

To determine the role of LPL for binding of lipoproteins to the vascular endothelium, and for the distribution of lipids from lipoproteins, four lines of induced mutant mice were used. Rat chylomicrons labeled in vivo with [(14)C]oleic acid (primarily in TGs, providing a tracer for lipolysis) and [(3)H]retinol (primarily in ester form, providing a tracer for the core lipids) were injected. TG label was cleared more rapidly than core label. There were no differences between the mouse lines in the rate at which core label was cleared. Two minutes after injection, about 5% of the core label, and hence chylomicron particles, were in the heart of WT mice. In mice that expressed LPL only in skeletal muscle, and had much reduced levels of LPL in the heart, binding of chylomicrons was reduced to 1%, whereas in mice that expressed LPL only in the heart, the binding was increased to over 10%. The same patterns of distribution were evident at 20 min when most of the label had been cleared. Thus, the amount of LPL expressed in muscle and heart governed both the binding of chylomicron particles and the assimilation of chylomicron lipids in the tissue.

Keywords: adipose tissue; heart; liver; muscle; nonesterified fatty acids; transgene; triglycerides.

Fig. 1.

Disappearance from the blood of core and TG label and appearance of radiolabeled FFAs. Doubly labeled rat lymph chylomicrons were injected intravenously into anesthetized mice. From each mouse, three blood samples were taken. One was at the end of the experiment, 20 min. The other samples were taken at two of the following times: 1, 2, 3, 7, or 13 min. Calculations are based on the weight of the sample and a blood volume of 7.7% of body weight. The left panels show core (filled diamonds) and TG label (filled squares). The scale is logarithmic. The right panels show FFAs (filled triangles). The scale is linear. Lines in the left panels show data fit for each group as described in Table 3. Values shown as mean ± SEM.

Fig. 2.

Chylomicron labels in the heart at 2 and 20 min. Doubly labeled rat lymph chylomicrons were injected intravenously into anesthetized mice. A final blood sample was taken 2 or 20 min later, and the animals were euthanized. The heart was immediately extirpated. The n = 6 in each group at 2 min (A); n as specified in Table 1 in the 20 min groups (B). Values are percent of injected dose per organ. LI, lipolysis index (TG label/core label, 1.0 in the chylomicrons as injected). Black bars, core label; gray bars, TG label. *P < 0.05, any of the genetically modified mice versus WT mice.

Fig. 3.

Chylomicron labels in M. quadriceps at 2 and 20 min. Same experiment as Fig. 2. Values shown as percent of injected dose per 100 mg wet weight.

Fig. 4.

Chylomicron labels in the liver at 2 or 20 min. Same experiment as Fig. 2. Values are percent of injected dose per organ.