A novel explanation for the reduced LDL cholesterol in severe hypertriglyceridemia.
When [3H]cholesteryl ester-labeled low density (LDL) and intermediate density lipoproteins (IDL) from a normotriglyceridemic, hypercholesterolemic rabbit were injected into severely hypertriglyceridemic, hypercholesterolemic rabbits, 60% of the label appeared in very low density lipoproteins (VLDL) at 3 hr. A similar experiment showed that 40% of injected 131I-protein-labeled LDL appeared in the IDL fraction at 4 hr. Taken together, these data suggest that the exchange of LDL cholesteryl ester for VLDL triglyceride results in a density shift of injected LDL to the IDL density range. Furthermore, the percent of injected 131I-labeled LDL from normotriglyceridemic rabbits that appeared in the IDL fraction increased in rabbits with increasing levels of plasma triglyceride. This LDL density shift was reproduced in vitro by incubating iodinated LDL from normotriglyceridemic, hypercholesterolemic rabbits with concentrations of VLDL from hypertriglyceridemic, hypercholesterolemic rabbits similar to those in plasma. With such a system, it was shown that the percentage of LDL that appeared in the IDL fraction increased with time, was enhanced fourfold by the addition of plasma lipid transfer protein, increased with increasing molar ratio of triglyceride to cholesteryl ester in VLDL, but apparently did not increase with increasing VLDL particle number. These studies suggest that a pronounced decrease in density of lipoproteins that would normally appear in the LDL density range, resulting from loss of cholesteryl ester in exchange for VLDL triglyceride, may explain, at least in part, the reduced LDL levels in severe hypertriglyceridemia.
Minnich
A
A
Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853.
Nordestgaard
B G
BG
Zilversmit
D B
DB
D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism*; D015243:Cholesterol, VLDL / Q000097:blood / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D005260:Female; D006937:Hypercholesterolemia / Q000139:chemically induced; D006951:Hyperlipoproteinemias / Q000139:chemically induced; D015228:Hypertriglyceridemia / Q000139:chemically induced / Q000378:metabolism*; D011817:Rabbits; D014280:Triglycerides / Q000097:blood
D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D014280:Triglycerides; D002784:Cholesterol