Low-density lipoproteins generated during an oral fat load in mild hypertriglyceridemic and healthy subjects are smaller, denser, and have an increased low-density lipoprotein receptor binding affinity.
Triglyceride-rich lipoproteins generated during the postprandial phase are atherogenic. Large very low-density lipoproteins (LDLs) or chylomicrons (CMs) are not as atherogenic as their remnants (Rem). Small and dense LDLs are associated with cardiovascular disease. Low-density lipoprotein size is partly under genetic control and is considered as a relatively stable LDL feature. In this article, we present data on retinyl palmitate kinetics correlated with the modification of LDL features in terms of size, density, and in vitro receptor binding affinity after an oral fat load. Six nondiabetic, hypertriglyceridemic (HTG) patients and 6 healthy controls were examined. Low-density lipoprotein size was assessed by gradient gel electrophoresis, and LDL density by density gradient ultracentrifugation. Low-density lipoprotein binding affinity was tested by in vitro competition binding assay on normal human skin fibroblasts (HSFs) and hepatoma cells (HepG2). Kinetic parameters were estimated in CM and Rem fractions by compartmental modeling. Hypertriglyceridemic patients showed significantly higher triglyceride area and a slower CM fractional catabolic rate. Postprandial LDL density increased both in HTG patients and in the control group with a significant difference between groups at 6 hours. Fasting LDL size was lower in HTG patients vs controls but decreased similarly in the postprandial phase. Low-density lipoprotein size and density postprandial modifications were not correlated with any investigated parameter. Postprandial LDLs were internalized more efficiently by HSF than baseline LDL only in the HTG group. In conclusion, postprandial LDLs are smaller and denser compared with fasting LDLs after an oral fat load. Postprandial LDLs also slightly increased their affinity to the HSF cell receptors.
Noto
Davide
D
Department of Internal Medicine, University of Palermo, I-90127 Palermo, Italy.
Rizzo
Manfredi
M
Barbagallo
Carlo Maria
CM
Cefalù
Angelo Baldassare
AB
Verde
Alessia Lo
AL
Fayer
Francesca
F
Notarbartolo
Alberto
A
Averna
Maurizio Rocco
MR
D000328:Adult; D001667:Binding, Competitive / Q000187:drug effects; D045744:Cell Line, Tumor; D002914:Chylomicrons / Q000737:chemistry / Q000378:metabolism; D004041:Dietary Fats / Q000494:pharmacology*; D004224:Diterpenes; D004591:Electrophoresis, Polyacrylamide Gel; D005215:Fasting; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood*; D007700:Kinetics; D008055:Lipids / Q000097:blood; D008077:Lipoproteins, LDL / Q000737:chemistry* / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D019518:Postprandial Period / Q000502:physiology; D011973:Receptors, LDL / Q000378:metabolism*; D000084562:Retinyl Esters; D014461:Ultracentrifugation; D014801:Vitamin A / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism
D002914:Chylomicrons; D004041:Dietary Fats; D004224:Diterpenes; D008055:Lipids; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D000084562:Retinyl Esters; D014801:Vitamin A; C014794:retinol palmitate