Is hypertriglyceridemic very low density lipoprotein a precursor of normal low density lipoprotein?

The precursor-product relationship of very low density (VLDL) and low density lipoproteins (LDL) was studied. VLDL obtained from normal (NTG) and hypertriglyceridemic (HTG) subjects was fractionated by zonal ultracentrifugation and subjected to in vitro lipolysis. The individual subfractions and their isolated lipolysis products, as well as IDL and LDL, were rigorously characterized. A striking difference in the contribution of cholesteryl ester to VLDL is noted. In NTG subfractions, the cholesteryl ester to protein ratio increases with decreasing density (VLDL-I----VLDL-III). This is the expected result of triglyceride loss through lipolysis and cholesteryl ester gain through core-lipid transfer protein action. In HTG subfractions there is an abnormal enrichment of cholesteryl esters that is most marked in VLDL-I and nearly absent in VLDL-III. Thus, the trend of the cholesteryl ester to protein ratios is reversed, being highest in HTG-VLDL-I and lowest in VLDL-III. This is incompatible with the precursor-product relationship described by the VLDL----IDL----LDL cascade. In vitro lipolysis studies support the conclusion that not all HTG-VLDL can be metabolized to LDL. While all NTG subfractions yield products that are LDL-like in size, density, and composition, only HTG-VLDL-III, whose composition is most similar to normal, does so. HTG VLDL-I and VLDL-II products are large and light populations that are highly enriched in cholesteryl ester. We suggest that this abnormal enrichment of HTG-VLDL with cholesteryl ester results from the prolonged action of core-lipid transfer protein on the slowly metabolized VLDL mass. This excess cholesteryl ester load, unaffected by the process of VLDL catabolism, remains entrapped within the abnormal particle. Therefore, lipolysis yields an abnormal, cholesteryl ester-rich product that can never become LDL.

[1]  Roger A. Renfrew,et al.  Lipid Research Clinics Program. , 1984, JAMA.

[2]  S. Eisenberg,et al.  Abnormalities in very low, low and high density lipoproteins in hypertriglyceridemia. Reversal toward normal with bezafibrate treatment. , 1984, The Journal of clinical investigation.

[3]  R. Gregg,et al.  Presence of two forms of apolipoprotein B in patients with dyslipoproteinemia. , 1983, Journal of lipid research.

[4]  P. Barter,et al.  Relative rates of incorporation of esterified cholesterol into human very low density lipoproteins and low density lipoproteins. In vitro studies of two separate pathways. , 1983, Biochimica et biophysica acta.

[5]  S. Eisenberg,et al.  Rat plasma lipoproteins: re-evaluation of a lipoprotein system in an animal devoid of cholesteryl ester transfer activity. , 1982, Journal of lipid research.

[6]  D. B. Zilversmit,et al.  Purification and characterization of lipid transfer protein(s) from human lipoprotein-deficient plasma. , 1982, Journal of lipid research.

[7]  L. Carlson,et al.  Composition, concentration, and size of low density lipoproteins and of subfractions of very low density lipoproteins from serum of normal men and women. , 1982, Journal of lipid research.

[8]  J. Kane,et al.  Heterogeneity of apolipoprotein B: isolation of a new species from human chylomicrons. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[9]  M. Kekki.  Plasma triglyceride turnover in 92 adult normolipaemic and 30 hypertriglyceridaemic subjects--the effect of age, synthesis rate and removal capacity on plasma triglyceride concentration. , 1980, Annals of clinical research.

[10]  Y. Barenholz,et al.  In vitro production of human plasma low density lipoprotein-like particles. A model for very low density lipoprotein catabolism. , 1979, The Journal of biological chemistry.

[11]  P. Nestel,et al.  Very Low Density Lipoprotein B‐Apoprotein Kinetics in Human Subjects: Relationships between Pool Size, Flux, and Removal Rate , 1979, Circulation research.

[12]  S. Grundy,et al.  Transport of very low density lipoprotein triglycerides in varying degrees of obesity and hypertriglyceridemia. , 1979, The Journal of clinical investigation.

[13]  P. Barter,et al.  In vitro exchanges of esterified cholesterol between serum lipoprotein fractions: studies of humans and rabbits. , 1979, Metabolism: clinical and experimental.

[14]  C. Packard,et al.  Very low density and low density lipoprotein subfractions in type III and type IV hyperlipoproteinemia. Chemical and physical properties. , 1979, Biochimica et biophysica acta.

[15]  P. Barter,et al.  The activity of an esterified cholesterol transferring factor in human and rat serum. , 1978, Biochimica et biophysica acta.

[16]  Y. Marcel,et al.  Cholesterol ester exchange between human plasma high and low density lipoproteins mediated by a plasma protein factor. , 1978, Atherosclerosis.

[17]  J. Patsch,et al.  Isolation of subfractions of human very low density lipoproteins by zonal ultracentrifugation. , 1978, The Journal of biological chemistry.

[18]  P. Nestel,et al.  Catabolism of very low density lipoprotein B apoprotein in man. , 1978, The Journal of clinical investigation.

[19]  L. Smith,et al.  Control of 3-hydroxy-3-methylglutaryl-CoA reductase activity in cultured human fibroblasts by very low density lipoproteins of subjects with hypertriglyceridemia. , 1978, The Journal of clinical investigation.

[20]  T. Olivecrona,et al.  Interaction of lipoprotein lipase with heparin-Sepharose. Evaluation of conditions for affinity binding. , 1977, The Biochemical journal.

[21]  B. Lewis,et al.  Metabolism of Very Low Density Lipoproteins in Hyperlipidaemia: Studies of Apolipoprotein B Kinetics in Man , 1976, European journal of clinical investigation.

[22]  B. Lewis,et al.  The Metabolism of Low Density Lipoprotein in Endogenous Hypertriglyceridaemia , 1976, European journal of clinical investigation.

[23]  D. B. Zilversmit,et al.  Stimulation of cholesterol ester exchange by lipoprotein-free rabbit plasma. , 1975, Biochimica et biophysica acta.

[24]  B. Lewis,et al.  Conversion of very low density lipoprotein to low density lipoprotein. A metabolic study of apolipoprotein B kinetics in human subjects. , 1975, The Journal of clinical investigation.

[25]  D. Bilheimer,et al.  On the metabolic conversion of human plasma very low density lipoprotein to low density lipoprotein. , 1973, Biochimica et biophysica acta.

[26]  D. Bilheimer,et al.  The metabolism of very low density lipoprotein proteins. II. Studies on the transfer of apoproteins between plasma lipoproteins. , 1972, Biochimica et biophysica acta.

[27]  S. Quarfordt,et al.  Heterogeneity of human very low density lipoproteins by gel filtration chromatography. , 1972, Journal of lipid research.

[28]  D. Bilheimer,et al.  The metabolism of very low density lipoprotein proteins. I. Preliminary in vitro and in vivo observations. , 1972, Biochimica et biophysica acta.

[29]  W. Hazzard,et al.  Very low density lipoprotein subfractions in a subject with broad-beta disease (Type 3 hyperlipoproteinemia) and a subject with endogenous lipemia (Type IV). Chemical composition and electrophoretic mobility. , 1970, Biochimica et biophysica acta.

[30]  K. Weber,et al.  The reliability of molecular weight determinations by dodecyl sulfate-polyacrylamide gel electrophoresis. , 1969, The Journal of biological chemistry.

[31]  L. Smith,et al.  EFFECT OF VERY LOW-DENSITY LIPOPROTEINS ON LIPID TRANSFER IN INCUBATED SERUM. , 1965, Journal of lipid research.

[32]  G. R. Bartlett.  Phosphorus assay in column chromatography. , 1959, The Journal of biological chemistry.

[33]  Oliver H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.

[34]  P. Kinnunen,et al.  In vitro catabolism of human very low density lipoproteins: fate of apoproteins B and C. , 1981, Artery.

[35]  F. Lindgren,et al.  Particle size and protein content of six fractions of the Sf 20 plasma lipoproteins isolated by density gradient centrifugation. , 1969, Journal of lipid research.