Accumulation of chylomicron remnants in homozygous subjects with familial hypercholesterolaemia.
BACKGROUND
Post-prandial lipoprotein kinetics were investigated in subjects who lack functioning low-density lipoprotein (LDL) receptors [homozygous familial hypercholesterolaemia (FH)].


METHODS
An oral fat load was given, and chylomicron plasma kinetics was determined by monitoring the clearance of triglyceride, retinyl palmitate and apolipoprotein B48, calculated as the area under the curve, for 7.5 h. In addition, the binding and uptake of chylomicron remnants by fibroblasts of FH and control subjects were assessed in vitro.


RESULTS
Based on the plasma kinetics of chylomicron triglyceride, retinyl palmitate and apolipoprotein B48 after a lipid meal, chylomicron clearance was found to be substantially delayed compared with normolipidaemic control subjects. Consistent with involvement of the LDL receptor in chylomicron clearance, binding and uptake of chylomicron remnants by fibroblasts of FH subjects was found to be substantially less than in cells from control subjects.


CONCLUSIONS
This study shows that, in addition to LDL, chylomicron metabolism is severely impaired in FH and that the LDL receptor is significantly involved in the clearance of post-prandial lipoproteins. Moreover, this study raises the possibility that in FH, and in other disorders in which LDL receptor expression is reduced, atherogenesis might be a post-prandial disease.
Mamo
J C
JC
Department of Physiology, University of Western Australia, Perth. jmamo@cyllene.uwa.edu.au
Smith
D
D
Yu
K C
KC
Kawaguchi
A
A
Harada-Shiba
M
M
Yamamura
T
T
Yamamoto
A
A
D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D002914:Chylomicrons / Q000097:blood / Q000378:metabolism*; D004224:Diterpenes; D005347:Fibroblasts / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D008074:Lipoproteins / Q000378:metabolism; D008875:Middle Aged; D019518:Postprandial Period; D011485:Protein Binding; D000084562:Retinyl Esters; D012867:Skin / Q000166:cytology; D014801:Vitamin A / Q000031:analogs & derivatives / Q000097:blood
D002914:Chylomicrons; D004224:Diterpenes; D008074:Lipoproteins; D000084562:Retinyl Esters; D014801:Vitamin A; C014794:retinol palmitate