Insulin stimulates receptor-mediated uptake of apoE-enriched lipoproteins and activated alpha 2-macroglobulin in adipocytes.
The low density lipoprotein receptor-related protein (LRP) is a cell surface receptor that binds and internalizes several macromolecules including apolipoprotein E-enriched remnant lipoproteins and protease/antiprotease complexes such as activated alpha 2-macroglobulin. Its function has been studied primarily in cultured fibroblasts and in liver. In the current studies, we provide evidence that LRP is present on the surface of primary adipocytes isolated from rat epididymal fat pads. The activity of the receptor increases 2-3-fold within minutes after the adipocytes are exposed to physiological concentrations of insulin as indicated by an increase in the uptake of 125I-labeled activated alpha 2-macroglobulin. There is a corresponding increase in the uptake of [3H]cholesteryl esters from radiolabeled apoE-enriched beta-very low density lipoprotein. The latter uptake was inhibited by an antibody against LRP and by a fusion protein containing the 39-kDa protein, also called receptor-associated protein, a known inhibitor of LRP function. In vivo, rats that had been fed ad libitum accumulated approximately 24-fold more chylomicron cholesteryl esters in their epididymal fat pads than did fasted control animals. We suggest that insulin stimulation of LRP, in a synergistic action with lipoprotein lipase, increases the endocytic uptake of cholesteryl esters and triglycerides from remnant lipoproteins in postprandial adipocytes.
Descamps
O
O
Department of Internal Medicine, University of Texas, Southwestern Medical Center, Dallas 75235.
Bilheimer
D
D
Herz
J
J
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D008055:Lipids / Q000096:biosynthesis; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011973:Receptors, LDL / Q000187:drug effects / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000494:pharmacology; D000511:alpha-Macroglobulins / Q000378:metabolism*
D001057:Apolipoproteins E; D007328:Insulin; D007457:Iodine Radioisotopes; D008055:Lipids; D008079:Lipoproteins, VLDL; D011973:Receptors, LDL; D011993:Recombinant Fusion Proteins; D000511:alpha-Macroglobulins; D005982:Glutathione Transferase; D005947:Glucose