Low Density Lipoprotein Apoprotein Research Articles

Endogenously labeled low density lipoprotein triglyceride and apoprotein B kinetics.

The kinetics of endogenously labeled low density lipoprotein (LDL) triglycerides (TG) and apoprotein B (apoB) have been studied in four normal and in four hyperlipemic subjects using double tracers. Analysis of the data suggests that most LDL triglycerides turn over about 10 times faster than apoB (0.003/min vs. 0.0003/min) and that about 10% of the LDL particles contain most of the TG found with LDL. It is not possible to determine from the analysis whether each new LDL particle arrives with the excess TG or whether only a subpopulation of particles contains most of the TG. The kinetic analysis further suggests that triglyceride-rich LDL particles do not exchange with an extraplasma compartment as most LDL particles do, and thus, they behave more like very low density lipoprotein particles. A compartmental model accounting for both the LDL-TG and LDL-apoB kinetics is proposed.

Carbohydrate composition of purified serum glycoproteins in Mucolipidosis II and Mucolipidosis III

Mucolipidosis II (I-cell disease) and Mucolipidosis III (ML III) are inherited disorders in which the molecular defect may involve an abnormality in a common post-translational modification step (possibly glycosylation) shared by lysosomal hydrolases. We tested whether such an alteration might be a generalized defect in glycoprotein biosynthesis and, thus, be reflected in an abnormal carbohydrate composition of non-lysosomal glycoproteins. The apoprotein of low density lipoprotein (apo-LDL) and immunoglobulin G (IgG) were purified to apparent homogeneity. Gas liquid chromatographic (glc) analysis of the carbohydrate content of these glycoproteins from ML II, ML III and normal sera revealed no differences in the relative ratios and total amounts of mannose, galactose, N-acetylglucosamine and sialic acid. These results suggest that if the postulated post-translational defect in these disorders involves changes in carbohydrate composition, it is not a general defect in glycosylation and may be specific for lysosomal hydrolases.

Sequences of Change in Low Density Lipoprotein Apoprotein Concentrations and Metabolism with Changes in Diet of Monkeys and Rabbits

Sequences of Change in Low Density Lipoprotein Apoprotein Concentrations and Metabolism with Changes in Diet of Monkeys and Rabbits

Effects of dietary saturated and polyunsaturated fat on the metabolism of apolipoproteins A-I and B: Study of a patient with type IIb hyperlipoproteinaemia

The effects of dietary saturated and polyunsaturated fat on the metabolism of apolipoprotein A-I (apoA-I) and apolipoprotein B (apoB) were studied in a patient with type IIb hyperlipoproteinaemia. On the saturated fat diet, the rate of synthesis of very low density lipoprotein apoprotein B (VLDL-apoB) was approximately twice normal, accounting for the increased plasma VLDL pool in this subject. However, 54% of the synthesized VLDL-apoB was catabolized by a pathway independent of low density lipoproteins (LDL). The metabolic conversion rate of VLDL-apoB to LDL-apoB was normal in this subject and his expanded plasma LDL-apoB pool resulted, not from increased input of the apoprotein from VLDL, but from a decrease in its fractional clearance rate. On the polyunsaturated diet, there was a significant fall in the plasma cholesterol and triglyceride concentrations and a change in the fatty acid composition of all plasma lipoprotein fractions. These changes were accompanied by a decrease in the plasma concentrations of apoA-I and apoB which resulted from a reduction of apoprotein synthetic rate.

Catabolism of the apoprotein of low density lipoproteins by the isolated perfused rat liver.

Isolated rat livers were perfused for 4 hours in a recirculating system containing washed rat erythrocytes. Biologically screened, radioiodinated low density lipoproteins (1.030 < d < 1.055 g/ml) were added to the perfusate with different amounts of whole serum to supply unlabeled rat low density lipoproteins. Apolipoprotein B contained 90% of the bound (131)I, other apolipoproteins contained 4%, and lipids contained the remainder. The fraction of apolipoprotein mass degraded during the perfusion was quantified by the linear increment of non-protein-bound radioiodine in the perfusate, corrected for the increment observed during recirculation of the perfusate in the absence of a liver. The fractional catabolic rate ranged from 0.3 to 1.7%/hr in seven experiments and was inversely related to the size of perfusate pool of low density apolipoprotein. The catabolic rate of low density apolipoprotein (fractional catabolic rate x pool size) in four livers, in which the concentration of rat low density lipoproteins was 50-100% of that present in intact rats, was 5.3 +/- 2.7 micro g hr(-1) (mean +/- SD). Similar results were obtained with human low density lipoproteins. These rates were compared with catabolic rates for the apoprotein of rat low density lipoproteins in intact animals. Fractional catabolic rate in vivo, obtained by multi-compartmental analysis of the disappearance curve of (131)I-labeled low density apolipoprotein from blood plasma, was 15.2 +/- 3.1% hr(-1) (mean +/- SD). Total catabolic rate in vivo (fractional catabolic rate x intravascular pool of low density apolipoprotein) was 76 +/- 14 micro g hr(-1) (mean +/- SD). The results suggest that only a small fraction of low density apolipoprotein mass in rats is degraded by the liver.

Proteolytic digestion in the elucidation of the structure of low density lipoprotein.

The apoprotein (apoB) of low density lipoprotein (LDL) is reported to be a large polypeptide, and it is proposed that there are two similar-sized subunit proteins in LDL (Smith, Dawson, and Tanford. 1972. J. Biol. Chem. 247: 3376-3381.). When apoB is isolated under conditions that minimize artifactual proteolysis, only a single, large molecular weight protein appears on polyacrylamide gel electrophoresis in SDS. To investigate the organization of apoB as it exists within native LDL, limited proteolysis with trypsin has been used as a structural probe. Tryptic digestion for 1 hr at pH 7.6 with enzyme-to-protein ratios of 1:100 and 1:5 results in the liberation of approximately 10% and 30% of apoB as smaller, water-soluble peptides. These peptides may be separated from the partially digested but still intact tryptic core (T-core) of the lipoprotein by chromatography on Sephadex G-75. Repeatedly, the 1:5 T-core of native LDL is found to contain a family of polypeptides of 14,000-100,000 molecular weight. Although they have lost significant quantities of apoprotein, these T-cores sustain an appearance of homogeneity, as studied by analytical ultracentrifugation. Their measured molecular weights do not differ appreciably from those of the native LDL, and the carbohydrate content of the 1:5 tryptic T-core of LDL is similar to that of the native LDL. In normolipemic individuals, LDL generally exists in a monodisperse state, but, in different individuals, monodisperse LDL may range in molecular weight from 2.4 to 3.9 x 10(6). Limited tryptic digestions were used to probe the organization of apoB in these different molecular weight LDL. As assayed by SDS-acrylamide gel electrophoresis of the larger polypeptides and fingerprinting of the smaller released peptides, those regions of LDL exposed to trypsin digestion are identical in monodisperse LDL of 2.5 and 3.4 x 10(6) molecular weight. Thus, the different quantities of lipid bound in these various LDL must interact with apoB so that the same regions of the apoprotein are exposed to the action of trypsin in these different molecular weight lipoproteins.

Studies of the cyanogen bromide fragments of the apoprotein of human serum low density lipoproteins

The apoprotein of human serum low density lipoproteins was reduced and carboxymethylated and then cleaved by cyanogen bromide (CNBr). The peptides which were produced from this cleavage (90% yield, based upon loss of methionine) were resolved by SDS polyacrylamide gel electrophoresis into 10 major bands, each having an amino acid composition very similar to that of intact reduced and carboxymethylated LDL apoprotein. The fractionation of the CNBr fragments by preparative gel filtration was dependent upon the nature of the eluting solvent. NH 4OH and SDS solvents eluted all of the material in the void volume. In 6 M guanidinium chloride solvents several peaks were, however, resolved, each having an amino acid composition similar to that of the unfractionated products. Whereas no NH 2-terminal was detected in reduced and carboxymethylated LDL apoprotein, automated Edman degradation of the protein following treatment with CNBr revealed the presence of several NH 2-termini. The results suggest that LDL apoprotein may be made of segments of, at least, very similar amino acid composition and that both the protein itself and derivative fragments have a great tendency to aggregate even in denaturing solvents.

The cyanogen bromide peptides of the apoprotein of low density lipoprotein (apoB): Its molecular weight from a chemical view

After >95% cleavage of the apoprotein (apoB) of the low density lipoproteins with cyanogen bromide, the peptides produced are shown to be extensively aggregated in sodium dodecyl sulfate. Both high temperature and increased concentration (5%) of the detergent are necessary to shift the aggregated peptides from high molecular weight (>25,000) to lower molecular weight aggregates as seen on sodium dodecyl sulfate polyacrylamide gel electrophoresis. End group analyses of the cyanogen bromide digestion by automated sequencer techniques indicate the presence of five (5) methionines. With a known methionine content of 16 moles/100,000 g protein, the molecular weight of the apoprotein must be approximately 30,000.

Plane Xanthoma and Multiple Myeloma With Lipoprotein—Paraprotein Complexing

Clinicopathologic findings are reported of a woman with generalized plane xanthoma, multiple myeloma (IgG type K), and hyperlipemia with very high levels of serum cholesterol and triglyceride. Complexing of the serum lipoproteins and immunoglobulins had cryoglobulin properties and was separable by ultracentrifugation. Immunofluorescent studies of skin and bone marrow demonstrated deposits of IgG with low density lipoprotein apoprotein and IgG with beta-lipoprotein, respectively. Although immunosuppressive therapy resulted in return of serum IgG, lipid, and lipoprotein levels to normal, the patient died from the myeloma. Serum lipoprotein-paraprotein complexes have been demonstrated in at least 20 other cases of cutaneous xanthomatosis and myeloma. This interaction may result in an autoimmune hyperlipemia.

Solubilization of apolipoprotein B and its specific binding by the cellular receptor for low density lipoprotein

Low density lipoprotein (LDL) and very low density lipoprotein (VLDL) bind specifically to a receptor on fibroblasts, and it has been postulated that the apoprotein of LDL (apo B) confers the specificity of cellular binding. This hypothesis has been tested in the present study with a watersoluble apo B-bovine serum albumin complex. The binding of (125)I-labeled apo B to cultured fibroblasts was temperature-dependent. Specific binding ranged between 183 and 859 ng/mg of cell protein at a concentration of 5 mug/ml; at 37 degrees , 750-2199 ng/mg was bound and internalized. The binding of apo B greatly exceeded the amount of (125)I-labeled LDL bound at 4 degrees and 37 degrees in the same experiment. Fibroblasts from a subject homozygous for hyper-beta-lipoproteinemia showed minimal binding of (125)I-labeled LDL, consistent with the absence of the cellular LDL receptor. Such cells also had depressed binding of (125)I-labeled apo B. Lymphocytes grown in lipoprotein-deficient medium demonstrated specific binding of LDL; however, freshly isolated lymphocytes did not show such binding. The binding of (125)I-labeled apo B to lymphocytes paralleled the binding of (125)I-labeled LDL. Unlabeled LDL and apo B-albumin complex both competitively inhibited the binding of (125)I-labeled apo B and (125)I-labeled LDL to fibroblasts. When labeled LDL was incubated with fibroblasts for 6 hr at 37 degrees , it underwent cellular internalization and degradation, as measured by the release of (125)I-labeled fragments into the medium. This degradation was inhibited by unlabeled apo B. Conversely, (125)I-labeled apo B also was internalized and degraded by fibroblasts, and this process was inhibited by LDL. These findings demonstrate that apo B binds specifically to the LDL receptor and that the cellular binding of LDL is determined by this apoprotein.

The Interaction of Heparin with an Apoprotein of Human Very Low Density Lipoprotein

An arginine-rich apoprotein obtained from human triglyceride-rich lipoprotein was isolated on a heparin affinity column when either the aqueousor urea-soluble apoproteins were applied to the column. Of all the aqueous- or urea-soluble apoproteins, only this arginine-rich protein exhibited a binding affinity to heparin. This protein was eluted from the column at sodium chloride concentrations above 0.35 M in the absence of urea and between 0.17-0.2 M when isolated in urea. The protein has been characterized by amino acid analysis, immunoelectrophoresis, dodecyl sulfate polyacrylamide electrophoresis, isoelectric focusing, and NH(2)-terminal analysis. It has the same amino acid composition, NH(2)-terminal, and molecular weight as previously described for human arginine-rich apoprotein. The triglyceride-rich lipoproteins of fasting normal humans were eluted as two fractions when applied to the heparin affinity column. A small amount was eluted in the unbound fraction and this species contained virtually no arginine-rich apoprotein. The bulk of the triglyceride-rich lipoproteins eluted in the bound fraction and contained appreciable amounts of arginine-rich apoprotein. The bound lipoproteins had more cholesterol and cholesterol ester and less triglyceride than the unbound. The isolated arginine-rich apoprotein was derivatized with phenylglyoxal with a resulting alteration of 75% of the arginine residues. This modified apoprotein did not bind to the heparin affinity column. Similar treatment of the whole triglyceride-rich lipoprotein produced a lipoprotein that was totally eluted in the unbound fraction.

Intravenous fat tolerance Correlation with very low density lipoprotein apoprotein b kinetics in man

The intravenous fat tolerance test (IVFTT) has been introduced as a measure of the fractional catabolic rate of the endogenous triglyceride of plasma. To assess the validity of this test we have compared this test in 21 normal and hyperlipidaemic subjects with direct measurement of the fractional catabolic rate of autologous radio-iodinated VLDL. There was a strong positive correlation between the rate constant K 2 of the IVFTT and the fractional catabolic rate of VLDL-apolipoprotein B ( r = +0.87). The two rates were considerably different in magnitude. The IVFTT appears to be a valid index of the fractional catabolic rate of VLDL. Its limitations and uses are discussed.

Quantification of apolipoprotein B in grossly normal human aorta.

A quantitiative electroimmunodiffusion (EID) assay was developed for apolipoprotein B (apoB), the major apoprotein of human plasma low density lipoproteins (LDL) and very low density lipoproteins (VLDL). Specificity, sensitivity (30-200 ng) and reproducibility (11%) were established. We used this system to determine the amount of buffer-soluble apoB in supernatant fractions from homogenates of the intima from grossly normal human aortas. Assays of whole tissue minces yielded only one-third of the apoB in supernatant fractions. Intimal homogenates contained 0.34-18.45 mug of apoB/mg of tissue, dry weight (mean 5.42 +/- 3.95 SD). We also found that no apoB was detected in the homogenates of adjacent tunica media. Furthermore, most of the intimal apoB was found in the LDL density (d) fraction (d 1.006-1.063) after differential ultracentrifugation, while the VLDL (d less than 1.006) fraction contained only negligible amounts of apoB. By electron microscopy, it was determined that the LDL density fraction contained particles 200-250 A in diameter which were similar in size to plasma LDL. These results suggest that grossly normal aortas contain significant quantities of intact LDL.

The effects of dietary fat and cholesterol on the metabolism of plasma low density lipoprotein apoproteins in squirrel monkeys

Low density lipoprotein apoproteins from squirrel monkeys ( Saimiri sciureus) had characteristic 2-phase die-away curves in plasma. The kinetic constants were similar with three methods of labeling: in vitro with 125I by the iodine monochloride or the Bolton-Hunter methods or in vivo by the injection of [ 3H]-leucine into a donor animal. Dietary cholesterol and the type of dietary fat influenced the concentration of plasma cholesterol and low density lipoproteins. The fractional turnover of low density lipoprotein apoprotein was greater in monkeys fed semipurified diets with safflower oil than in those on butter but was not influenced by dietary cholesterol. The total low density lipoprotein apoprotein turnover (the product of fractional turnover and plasma lipoprotein concentration) was highest in monkeys fed butter plus added cholesterol and lowest in those on safflower oil without cholesterol. Dietary safflower oil resulted in a smaller proportion of the total low density lipoprotein pool in the intravascular compartment than did butter, regardless of whether cholesterol was added.

Low density lipoprotein metabolism in a family of familial hypercholesterolemic patients

A low-density lipoprotein turnover study was performed on six heterozygous familial hypercholesterolemic subjects and five control subjects. The diagnosis of the condition was clear-cut on biochemical, clinical, and genetic grounds. Kinetic analysis of the plasma decay curves gave the following mean values: (1) The plasma concentration of low density lipoprotein apoprotein (apoLDL) in the affected subjects was 247 mg/dl, a 2.5-fold increase over control values (98 mg/dl). (2) The calculated fractional catabolic rate of the intravascular apoLDL pool in the dyslipoproteinemics was reduced with respect to control data (16.4%/day versus 31.2%/day), and the half-life of the apolipoprotein was correspondingly increased (6.07 days versus 3.63 days). (3) The absolute catabolic rate of the apoLDL was 15.6 mg/kg/day in contrast to the lower value of 11.6 mg/kg/day in the control group. (4) A strong negative correlation was observed between the plasma apoLDL concentration and the fractional catabolic rate ( r = 0.96). We conclude from our data that increased apoLDL synthesis coupled with a defective or saturated catabolic mechanism is implicated in the pathogenesis of familial hypercholesterolemia.

Incorporation of 75Se-Selenomethionine into Human Apoproteins: III. Kinetic Behavior of Isotopically Labeled Plasma Apoprotein in Man

The metabolism of lipoprotein-apoprotein was examined in four subjects with normal lipid metabolism and in one subject with type II hyperlipemia by means of isotopic tracer methodology. Studies were performed after intravenous injection of a radioactive amino acid precursor for apoprotein synthesis (75Se-selenomethionine), in both the basal state and following the acute injection of intravenous heparin. Computer technics were used to evaluate a series of multicompartmental models, and a general model is proposed that yields optimum fitting of experimental data for serum free amino acid precursor, very-low-density lipoprotein-apoprotein (VLD-apoprotein), and low-density lipoprotein-apoprotein (LDL-apoprotein) in man. The analysis demonstrates that approximately half of the transport of 75Se-apoVLDL from the plasma VLDL pool is converted to 75Se-apoLDL. The acute injection of heparin in two normal subjects results in a two-and-a-half-fold increase in this rate of conversion of 75Se-apoVLDL to 75Se-apoLDL. 75Se-apoLDL is metabolized by rapid transport into a recycling extravascular pool and by irreversible catabolism. The fractional rate of recycling is large relative to the fractional rate of catabolism of apoLDL (3.7:1.0), suggesting extravascular recycling as a potential site of regulation of the plasma concentration of apoLDL. In a patient with type II hyperlipemia, the extravascular recycling pathway is reduced and is not corrected with D-thyroxine therapy. However, this therapy did reduce conversion of apoVLDL to apoLDL in this type II patient. The kinetic data support the validity of the compartmental model in simulating both normal and pathologic apoprotein metabolism and that perturbation of physiology seen with heparin injection and D-thyroxine therapy. These data support a quantitative role of apoVLDL as a precursor of apoLDL and identify an important recycling pathway of apoLDL metabolism in addition to that of catabolism.

Uptake and catabolism of low density lipoprotein by human lymphocytes

BROWN and Goldstein1,2 have shown that when cultured human fibroblasts are incubated in the presence of low density lipoprotein (LDL), they take up some LDL, the apoprotein of LDL (apoLDL) is catabolised and cholesterol synthesis is inhibited. Experiments on the uptake of LDL as a function of LDL concentration have led to the conclusion1,2 that normal fibroblasts have genetically controlled surface receptors with high affinity for apoLDL and that uptake of LDL by the receptors is essential for the regulation of cholesterol synthesis. These findings raise the possibility that receptor-mediated uptake by fibroblasts, and perhaps by other cells3,4, has an important role in the regulation of apoLDL catabolism and of cholesterol synthesis in vivo. But the concentration of LDL protein required to saturate the LDL receptors on cultured fibroblasts (about 50 µg ml−1) is less than half the probable concentration in interstitial fluid5. Moreover, whereas cultured fibroblasts from patients with familial hypercholesterolaemia (FH) in the homozygous form synthesise cholesterol at 50 times the normal rate, the rate of synthesis of cholesterol in the whole bodies of FH patients is usually normal6 or subnormal7. For these reasons it seemed desirable to study the binding and catabolism of LDL by uncultured human cells. We used circulating lymphocytes because they can be obtained readily and repeatedly from healthy human subjects. Our results show that uncultured lymphocytes exhibit high capacity surface binding of LDL, but the binding curves show no evidence for the presence of high affinity receptors for LDL.

Uptake and degradation of low density lipoprotein by swine arterial smooth muscle cells with inhibition of cholesterol biosynthesis

We have previously proposed on the basis of studies in hepatectomized animals that low density lipoproteins are degraded at a significant rate by peripheral tissues. To test the capacity of one peripheral cell type to catabolize low density lipoprotein, cultures of swine aortic smooth muscle cells were incubated with homologous 125I-labeled low density lipoprotein and uptake and degradation measured. Degradation of 125I-labeled low density lipoprotein to products soluble in trichloroacetic acid showed an initial lag period of 1–2 h after which the rate increased and remained linear for the following 15 h. Rates of degradation increased sharply with low density lipoprotein concentration over the lower range (from 0–25μg protein/ml) and then more slowly up to the highest concentration tested, 300 μg protein/ml. Even at very low concentrations, 1 μg low density lipoprotein protein/ml (less than 10% of the plasma low density lipoprotein concentration), the in vitro degradation rate (per kg of smooth muscle cells) exceeded the in vivo degradation rate (per kg of total body weight). To the extent that smooth muscle cells are representative of other peripheral cells, the results support the proposal that peripheral degradation of low density lipoprotein apoprotein may be quantitatively important. The rate of incorporation of labeled acetate into sterols was suppressed in cells incubated with whole serum, low density and very low density lipoproteins, or suspensions of free cholesterol. In this respect, the results were similar to those observed in human skin fibroblasts studied concurrently. However, high density lipoprotein inhibited sterol synthesis by about 25% in swine smooth muscle cells while it had no effect in human skin fibroblasts. Cells incubated overnight in lipoprotein-deficient medium showed a net decrease in cholesterol content which could be restored by incubating with low density lipoprotein but not with high density lipoprotein. At high concentrations of low density lipoprotein, when uptake and degradation proceed at very high rates, the amount of cholesterol delivered to the cell is in excess of observed net changes in cell cholesterol content. These findings suggest that there may be a very active “reverse cholesterol transport” in vivo carrying cholesterol from peripheral cells (in which low density lipoprotein is being degraded) back to the liver for ultimate metabolism and excretion.

The Metabolism of Low Density Lipoprotein in Endogenous Hypertriglyceridaemia

The metabolism of low density lipoprotein (LDL) was studied in eighteen hypertriglyceridaemic patients by injecting autologous radioiodinated LDL. Over 95% of the label was bound to the protein moiety of LDL and therefore the metabolic data reflect the fate and distribution of LDL apoprotein (apo B). The hypertriglyceridaemic subjects included ten with Type V, five with Type IV, two with Type III and one with Type IIb hyperlipoproteinaemia. For comparison identical studies were carried out in seven normal subjects and five patients with heterozygous familial hyperbetalipoproteinaemia (Type IIa). The groups differed considerably in mean LDL-cholesterol concentration. The patients with Type V lipoprotein pattern had significantly lower LDL-cholesterol concentration (mean 0.754 g/1) than the normal group (mean 1.237 g/1). Raised LDL-cholesterol levels were observed in all patients with heterozygous familial hyperbetalipoproteinaemia. The synthetic rate of LDL-apoprotein was found to be similar in all three groups (hypertriglyceridaemic, normal and hypercholesterolaemic). The highest synthetic rate was observed in the patient with Type IIb pattern. However, the fractional catabolic rate (FCR) of LDL-apoprotein differed significantly. The highest mean FCR was found in the Type V group (0.65 +/- 0.17 day-1) compared with 0.41 +/- 0.09 day-1 in the normal group and 0.185 +/- 0.05 day-1 in the Type IIa group. A strong inverse correlation was found between FCR and LDL apoprotein concentration in the whole series (r = -0.90, p less than 0.001) as well as within the Type V group (r = -0.87, p less than 0.01). These data indicate that the low plasma levels of LDL frequently observed in patients with very high plasma triglyceride levels are due to a high removal rate of LDL in these patients rather than to abnormal LDL synthesis.

Apoproteins of the lipoproteins in a nonrecirculating perfusate of rat liver

The apoproteins of serum lipoproteins and of lipoproteins present in a nonrecirculating perfusate of rat liver were compared by immunochemical, gel electrophoretic, and solubility techniques. Serum and perfusate very low density lipoprotein apoprotein composition were not different. No evidence for the presence of a lipoprotein resembling serum low density lipoprotein was obtained. However, the apoprotein composition of circulatory high density lipoprotein was quantitatively different from the secretory product in the density 1.06-1.21 range. As measured by stained sodium dodecyl sulfate gel electrophoretic patterns, the arginine-rich protein was the major secretory apoprotein while the A-I protein was the major apoprotein in circulating high density lipoprotein. A very similar pattern was seen in perfusates of orotic acid-fatty livers. It was concluded that although the liver secrets lipoproteins in the high density class, circulatory high density lipoprotein is largely a product of catabolic processes.