The role of lipoprotein lipase in the metabolism of triglyceride-rich lipoproteins by macrophages.
We have previously shown that cultured macrophages secrete lipoprotein lipase (LPL) into the culture medium. The purpose of these experiments was to determine the role of LPL in the uptake of very low density lipoproteins (VLDL). Both J774 cells and mouse peritoneal macrophages took up and degraded normotriglyceridemic VLDL in a saturable manner. Uptake of VLDL was effectively competed for by rabbit beta-VLDL, human VLDL, but not by native LDL or acetyl LDL. LPL activity accelerated saturable uptake of VLDL but was not a prerequisite for it. This was most clearly seen in experiments with apo-C-II-deficient VLDL. Although no hydrolysis of VLDL triglyceride occurred, saturable uptake and degradation of the C-II-deficient lipoprotein occurred. However, addition of apo-C-II enhanced saturable uptake. Normal VLDL also promoted cellular accumulation of both triglycerides and cholesteryl esters. Accumulation of triglyceride occurred by uptake of intact VLDL particles, by uptake of a triglyceride-depleted particle produced by the action of LPL, and by the direct uptake of free fatty acids generated by the activity of LPL. In turn, the latter process was influenced by the amount of albumin in the medium capable of being an acceptor for free fatty acids. Finally, we have shown that when albumin is present in the medium, the macrophage is capable of mobilizing most of its stored triglyceride over 24 h, even as its cholesteryl ester content remains constant. These studies may be relevant to the ability of VLDL to promote macrophage accumulation of cholesteryl ester, even as triglyceride accumulation is minimized.
D000818:Animals; D053304:Apolipoprotein C-II; D001053:Apolipoproteins / Q000494:pharmacology; D001056:Apolipoproteins C; D002738:Chloroquine / Q000494:pharmacology; D002784:Cholesterol / Q000032:analysis; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D008055:Lipids / Q000032:analysis; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice
D053304:Apolipoprotein C-II; D001053:Apolipoproteins; D001056:Apolipoproteins C; D005230:Fatty Acids, Nonesterified; D008055:Lipids; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D002738:Chloroquine; D002784:Cholesterol; D008071:Lipoprotein Lipase