In vitro lipolysis of human VLDL: effect of different VLDL compositions in normolipidemia, familial combined hyperlipidemia and familial hypertriglyceridemia.
Suboptimal lipolysis of very low density lipoproteins (VLDL) due to reduced substrate affinity for lipoprotein lipase (LPL) may contribute to the accumulation of apolipoprotein (apo) B in familial combined hyperlipidemia (FCH) or the characteristic increase in triglyceride-rich lipoproteins in familial hypertriglyceridemia (FHTG). To investigate this hypothesis in detail, the VLDL composition and substrate affinity for lipoprotein lipase was determined in 22 normolipidemic controls, 16 FCH probands, and 12 FHTG subjects. VLDL from FCH subjects were enriched in cholesterol and phospholipid. VLDL from FHTG subjects were enriched in triglycerides, cholesterol and phospholipid. Potential apolipoprotein regulators of LPL activity including apo C-II, apo C-III and apo E were not significantly different between FCH and controls when expressed per VLDL apo B. High apo C-III concentrations were present in FHTG-VLDL, and the apo C-III/E-ratio was significantly higher than in FCH- and control-VLDL. An increase of C-III-0, the desialylated isoform, was observed in FHTG-VLDL. The kinetic indicators for in vitro triglyceride hydrolysis by LPL, KM and VMAX, were not significantly different between the groups. KM values measured in vitro were remarkably and consistently high (1.54 mmol VLDL-TG/I), predicting saturation of LPL when VLDL-TG levels exceed 5.5 mmol/l (2 times KM + 2S.D.). In conclusion, VLDL from individuals with FCH or FHTG are normal substrate for lipoprotein lipase in spite of significant differences in lipid and apolipoprotein composition. The high apo C-III content of FHTG-VLDL supports a role in the expression of hypertriglyceridemia.
van Barlingen
H H
HH
Department of Internal Medicine, University Hospital, Utrecht University, The Netherlands.
Kock
L A
LA
de Man
F H
FH
Erkelens
D W
DW
de Bruin
T W
TW
D000818:Animals; D001053:Apolipoproteins / Q000097:blood; D002417:Cattle; D002474:Cell-Free System; D002784:Cholesterol / Q000097:blood; D006801:Humans; D006868:Hydrolysis; D006950:Hyperlipidemia, Familial Combined / Q000097:blood*; D006953:Hyperlipoproteinemia Type IV / Q000097:blood*; D007700:Kinetics; D008066:Lipolysis; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008079:Lipoproteins, VLDL / Q000737:chemistry / Q000378:metabolism*; D010743:Phospholipids / Q000097:blood; D013379:Substrate Specificity; D014280:Triglycerides / Q000097:blood
D001053:Apolipoproteins; D008079:Lipoproteins, VLDL; D010743:Phospholipids; D014280:Triglycerides; D002784:Cholesterol; D008071:Lipoprotein Lipase