Metabolism of lipoproteins in nonhuman primates. Studies on the origin of low density lipoprotein apoprotein in the plasma of the squirrel monkey.

The plasma of squirrel monkeys contains extremely low levels of very low density lipoproteins. The delipidated apoproteins from the different lipoprotein density classes of this species show a heterogeneity similar to that of man and the rat. The biosynthesis of the apoproteins of squirrel monkey lipoproteins was studied in fasted normal and Triton WR1339-treated animals. After intravenous injection of [3-H] leucine, maximal labeling of very low density lipoproteins occurred after 1 h, intermediate density lipoproteins (d 1.006--1.019) in 2 h, and low density lipoproteins after 3 h. At all times, however, low density lipoproteins had the greatest percentage of radioactivity. Polyacrylamide gel electrophoresis revealed that the apoprotein B moiety of very low density and intermediate density lipoproteins contained 62% and 81% of the total radioactivity in these lipoproteins whereas the fast-migrating peptides were minimally labeled. In monkeys injected with Triton WR1339, 70--80% of the radioactivity incorporated into d smaller than 1.063 lipoproteins was in very low density lipoproteins with only 10--15% in intermediate and low density lipoproteins. After injection of 3-H-labeled very low density lipoproteins and [14-C] leucine into Triton-treated monkeys, catabolism of 3-H-labeled very low density lipoprotein to intermediate and low density lipoproteins was small and was significantly less than corresponding values for the incorporation of [14-C] leucine. Thus, breakdown of very low density lipoproteins could not account for all the labeled apoprotein B present in the intermediate and low density lipoprotein fractions. The results indicate that most, but not all, of the newly synthesized apoprotein B enters plasma in very low density lipoproteins and that the low concentrations of this lipoprotein in squirrel monkey plasma are a consequence of its rapid turnover.     

Intestinal lipoprotein synthesis. Comparison of nascent Golgi lipoproteins from chow-fed and hypercholesterolemic rats

Hypercholesterolemia, induced by a cholesterol-enriched diet, is associated with distinctive modifications in the serum lipoproteins of a variety of species. Present in the serum of these animals are several classes of lipoproteins enriched in cholesteryl esters and apolipoprotein E. To investigate the role of intestinal lipoprotein synthesis in diet-induced hypercholesterolemia, we characterized nascent lipoproteins retrieved from Golgi apparatus-rich fractions of intestinal epithelial cells from chow-fed control and hypercholesterolemic rats. To eliminate chylomicrons from the preparations, rats were fasted overnight prior to the experiments. Golgi very low density lipoproteins (d less than 1.006 g/ml) from control rats were triglyceride-rich lipoproteins that migrated slightly slower than pre-beta migrating serum very low density lipoproteins. These particles contained apoproteins B-240, A-IV, and A-I. Golgi very low density lipoproteins from hypercholesterolemic rats were likewise triglyceride-rich lipoproteins migrating electrophoretically like control Golgi very low density lipoproteins and they contained apoproteins B-240, A-IV, and A-I. However, these latter particles contained less triglyceride and more cholesterol compared to control Golgi very low density lipoproteins. In addition, by radioisotope incorporation studies, Golgi very low density lipoproteins from hypercholesterolemic rats contained relatively more apoprotein A-IV (21.6 vs. 11.0%) and less apoprotein B-240 (17.0 vs. 27.0%) than found in control Golgi very low density lipoproteins. Approximately 60% of the total apoprotein radioactivity was found in apoprotein A-I in both preparations. We conclude that intestinal lipoprotein synthesis is modified by diet-induced hypercholesterolemia. The significance of these modifications with respect to the marked hypercholesterolemia observed in these animals remains to be determined.     

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.     

Characterization of human very low density lipoproteins containing two electrophoretic populations: double pre-beta lipoproteinemia and primary dysbetalipoproteinemia.

Two discrete populations of very low density lipoproteins, with fast and slow pre-beta electrophoretic mobility, were found in 50% of normolipemic and 30% of hyperlipemic individuals selected at random. The two populations were isolated by preparative electrophoresis from five hyperlipemic subjects. The particles comprising the slow component were smaller than those of the fast component and the slow component contained a larger proportion of cholesteryl esters, free cholesterol, B-apoprotein, and arginine-rich apoprotein and a smaller proportion of triglycerides and the two most anionic apoproteins (R-glutamic acid and R-alanine). The properties of the slow component thus closely resemble those of "remnant" very low density lipoproteins that accumulate in blood plasma of functionally hepatectomized rats. The chemical composition of the slow component was also similar to that of the very low density lipoproteins with beta mobility found in primary dysbetalipoproteinemia. However, the proportion of cholesteryl esters and argininerich apoprotein was much higher in the latter. The argininerich apoprotein from very low density lipoproteins of most normolipemic and hyperlipemic subjects separates into three or four major bands upon isoelectric focusing electrophoresis in polyacrylamide gels, with pI varying from 5.57 to 6.03. In very low density lipoproteins from individuals with primary dysbetalipoproteinemia, this protein uniquely contains little or none of the two most cationic bands. The number of bands was constant in all subjects studied. The pattern was the same in very low density lipoproteins with fast and slow pre-beta mobility as well as in the beta and pre-beta components in primary dysbetalipoproteinemia. These results suggest that many individuals have "remnant" very low density lipoproteins in their plasma. However, the beta-migrating "remnant" that accumulated in large amounts in individuals with primary dysbetalipoproteinemia contains much more arginine-rich protein and this protein is structurally abnormal.     

The turnover of human plasma very low density lipoprotein protein.

The plasma decay of three groups of iodinated apoproteins on human very low density lipoproteins were evauluated in two normals, two subjects with endogenous hypertriglyceridemia and another two with dysbetalipoproteinemia. The apo beta decay was more rapid than that of the C apoproteins in all patients. The apo beta decay was more rapid for the normals than for either the subjects with hypertriglyceridemia or dysbetalipoprotenemia. The apo C protein had an irregular decay in the normals but decayed less irregularly for the hypertriglyceridemics. The arginine rich apoprotein had a decay somewhat similar to apo C protein in the normals. The apo beta protein of the alpha2 very low density lipoprotein of a dysbetalipoproteinemic was consistent with a precursor relationship to the apo beta of beta very low density lipoprotein of this subject, but the arginine rich apoprotein was not.     

Separation and characterization of plasma lipoproteins of rhesus monkeys (Macaca mulatta).

A group of 14 adult male rhesus monkeys was maintained on a low cholesterol-high fat diet. Periodically, animals were fasted and blood samples were taken for characterization of the plasma lipoproteins. Complete separation of individual plasma lipoprotein classes was not achieved by traditional sequential ultracentrifugation techniques. Rather, initial separation of lipoprotein classes according to size was effected and density centrifugation was used subsequently for further separation. At least six lipoprotein fractions were identified, each of which was unique as defined by the properties of size, density (d), and electrophoretic mobility. These lipoprotein fractions were characterized by determination of chemical compositions and apoprotein patterns. The lipoproteins present in highest concentration in these monkeys were designated as region IV lipoproteins. This fraction had alpha-migration on agarose electrophoresis, 1.063 < d < 1.225, and the size, composition, and apoprotein pattern characteristic of HDL. No fewer than three fractions were identified with densities that overlapped the 1.019 < d < 1.063 range. Of these, the fraction designated as region III lipoproteins was present in highest concentration, had beta-migration by agarose electrophoresis, a predominant B apoprotein, and a chemical composition and size characteristic of LDL. Two larger subfractions, identified as region II lipoproteins, were separated from each other at a density of 1.050 g/ml. Agarose electrophoresis showed that the fraction with d < 1.050 had a migration intermediate between beta and pre-beta. The chemical composition and apoprotein pattern were consistent with the possibility that these lipoproteins were remnants of VLDL catabolism. The fraction with d > 1.050, had pre-beta mobility and a size and composition similar to the Lp(a) lipoprotein in plasma of human beings. At least two VLDL subfractions, identified as region I and IIa lipoproteins, were found although both were present in very low concentrations. Region I lipoproteins were larger and contained relatively more cholesteryl ester and more of the apoproteins that migrated with the mobility of apo-B and arg-rich apoprotein in SDS-polyacrylamide gel electrophoresis. Some of the region I lipoproteins were beta-migrating by agarose electrophoresis. These results suggested the possibility that a beta-migrating VLDL was present in these normal animals.     

Cord blood plasma lipoproteins inhibit mitogen-stimulated lymphocyte proliferation

Lipoproteins were isolated from adult plasma and the umbilical cord blood plasma of newborn infants and were compared for their capacity to inhibit mitogen-stimulated [3H]thymidine uptake of adult peripheral blood mononuclear cells in vitro. Relative to the comparable adult lipoproteins, cord blood low density lipoproteins and high density lipoproteins inhibited mitogen stimulation at twofold to fourfold lower total protein concentrations. Apoproteins AI, B, and E were quantitated by radioimmunoassay of each of the adult and cord blood lipoprotein fractions. A strong correlation was observed between inhibitory activity and the amount of apoprotein E in the cord blood low and high density lipoproteins. Further evidence that lipoproteins containing apoprotein E accounted for the difference in suppressive activity of cord blood low and high density lipoproteins relative to the adult lipoproteins was obtained by selective removal of the apoprotein E-containing lipoproteins by using immunoaffinity chromatography or heparin-agarose adsorption. The results indicated that cord blood lipoproteins containing apoprotein E in association with apoproteins AI or B are capable of suppressing lymphocyte proliferation in vitro.     

Heterogeneity of lipoprotein B

Combined very low and low density lipoproteins were derived from human plasma by polyanion precipitation and the low density lipoprotein fraction (density 1.027–1.050 g/ml) was isolated by sequential ultracentrifugation. When this fraction was applied to Sepharose column chromatography, three lipoproteins were eluted. The first and third peaks were minor components while the second peak represented the bulk of LDL. Further chromatographic and electrophoretic studies indicated that the component representing the second peak was heterogeneous. This component was subsequently delipidated at pH 4 in a quaternary biphasic solvent system. The apoproteins remained soluble after delipidation and were treated with various deaggregating agents. On column isoelectric focusing in the presence of 4 M urea the apoproteins banded as broad overlapping peaks between pH 3 and 7. When hexanol was added to the system, distinct apoprotein subfractions were resolved.     

Apolipoproteins of high, low, and very low density lipoproteins in human bile

We tested the hypothesis that apolipoproteins, the protein constituents of plasma lipoproteins, are secreted into bile. We examined human gallbladder bile obtained at surgery (N = 54) from subjects with (N = 44) and without (N = 10) gallstones and hepatic bile collected by T-tube drainage (N = 9) after cholecystectomy. Using specific radioimmunoassays for human apolipoproteins A-I and A-II, the major apoproteins of high density lipoproteins, for apolipoproteins C-II and C-III, major apoproteins of very low density lipoproteins, and for apolipoprotein B, the major apoprotein of low density lipoproteins, we found immunoreactivity for these five apolipoproteins in every bile sample studied in concentrations up to 10% of their plasma values. Using double immunodiffusion, we observed complete lines of identity between bile samples and purified apolipoproteins A-I, A-II, or C-II. Using molecular sieve chromatography, we found identical elution profiles for biliary apolipoproteins A-I, A-II and B and these same apolipoproteins purified from human plasma. When we added high density lipoproteins purified from human plasma to lipoprotein-free solutions perfusing isolated rat livers, we detected apolipoproteins A-I and A-II in bile. Similarly, when we added low density lipoproteins purified from human plasma to lipoprotein-free solutions perfusing isolated livers of rats treated with ethinyl estradiol in order to enhance hepatic uptake of low-density lipoproteins, we found apolipoprotein B in bile. These data indicate that apolipoproteins can be transported across the hepatocyte and secreted into bile.     

A rapid electrophoretic technique for identification of subunit species of apoproteins in serum lipoproteins

The denaturing solvent tetramethylurea (TMU) delipidates and quantitatively liberates the apoproteins of human serum high-density lipoprotein (HDL) in soluble form while virtually the whole apoprotein of human lowdensity lipoprotein (LDL) is precipitated. A fraction of the apoprotein of very low density lipoprotein (VLDL) which appears to represent its content of LDL-like protein (apo B) is precipitated by this reagent, while the remaining apoprotein species are liberated in soluble form.The dissociation of the soluble apoproteins from lipid by TMU obviates the need for time-consuming delipidation by organic solvents, permitting immediate electrophoretic analysis in polyacrylamide gels. Bands are observed with mobilities corresponding to those of all the major soluble polypeptide species isolated from serum lipoproteins by ion-exchange chromatography. The apparent distribution of these elements in the different classes of lipoproteins is in agreement with findings of studies employing chromatographic methods. The predominant apoprotein of HDL, which has been identified immunochemically in VLDL, appears to comprise less than 1% of the apoprotein of VLDL from normal serum.     

Swine lipoproteins and atherosclerosis. Changes in the plasma lipoproteins and apoproteins induced by cholesterol feeding.

Cholesterol feeding in miniature swine resulted in a hypercholesterolemia with a distinctive hyperlipoproteinemia and the subsequent development of atherosclerosis. Alterations in the type and distribution of plasma lipoproteins induced by cholesterol feeding were as follows: (a) the occurrence of beta-migrating lipoproteins (B-VLDL) as well as very low density lipoproteins in the d less than 1.006 ultracentrifugal fraction; (b) an increased prominence of the intermediate lipoproteins (d = 1.006-1.02); (c) an increased prominence of low density lipoproteins; and (d) the occurrence of a distinctive lipoprotein with alpha mobility which was referred to as HDLc (cholesterol induced). Characterization of the various plasma lipoproteins included chemical composition, size by electron microscopy, and apoprotein content. The B-VLDL resembled the beta-migrating lipoproteins of human Type III hyperlipoproteinemia and contained a prominent protein equivalent to the arginine-rich apoprotein in addition to the B apoprotein, apo-A-I, and the fast-migrating apoproteins (apo-C). The HDLc were rich in cholesterol, ranged in size from 100 to 240 A in diameter, and contained the arginine-rich apoprotein and apo-A0I but lacked the B apoprotein. The arginine-rich apoproteins isolated from B-VLDL and HDLc by gel chromatography were similar in amino acid analyses, with glutamic acid as their amino-terminal residue. The occurrence of a spectrum of cholesterol-rich lipoproteins which contained the arginine-rich apoprotein with the occurrence of accelerated atherosclerosis suggested an interesting, although speculative, association.     

Equilibrium of apoproteins between high density lipoprotein and the aqueous phase: modelling of in vivo metabolism

There is a growing body of evidence that apoproteins of the high density lipoproteins (HDL) exchange between lipoprotein particles through the aqueous phase and that there is always a finite but physiologically important quantity of lipid-free apoprotein in plasma. We have studied the theoretical consequences of this concept on the catabolism of apoproteins and developed a testable model for studying the in vivo metabolism of HDL apoproteins. This model describes the putative modification of the apparent tissue distribution spaces of the apoprotein that would result from a change in the partitioning of this apoprotein between HDL and the aqueous phase. The main parameters predicted by the model include the tissue distribution spaces of free monomeric apoprotein, those of HDL-bound apoprotein and the partition coefficient of the apoprotein between HDL and the aqueous phase in blood. We have designed several ways of testing this model in vivo including the use of model synthetic apoproteins. This model can be generalized to a number of other binding systems.     

The estradiol-stimulated lipoprotein receptor of rat liver. A binding site that membrane mediates the uptake of rat lipoproteins containing apoproteins B and E

Hepatic catabolism of lipoproteins containing apolipoproteins B or E is enhanced in rats treated with pharmacologic doses of 17 alpha-ethinyl estradiol. Liver membranes prepared from these rats exhibit an increased number of receptor sites that bind 125I-labeled human low density lipoproteins (LDL) in vitro. In the present studies, this estradiol-stimulated hepatic receptor was shown to recognize the following rat lipoproteins: LDL, very low density lipoproteins obtained from liver perfusates (hepatic VLDL), and VLDL-remnants prepared by intravenous injection of hepatic VLDL into functionally eviscerated rats. The receptor also recognized synthetic lamellar complexes of lecithin and rat apoprotein E as well as canine high density lipoproteins containing apoprotein E (apo E-HDLc). It did not recognize human HDL or rat HDL deficient in apoprotein E. Much smaller amounts of this high affinity binding site were also found on liver membranes from untreated rats, the number of such sites increasing more than 10-fold after the animals were treated with estradiol. Each of the rat lipoproteins recognized by this receptor was taken up more rapidly by perfused livers from estrogen-treated rats. In addition, enrichment of hepatic VLDL with C-apoproteins lowered the ability of these lipoproteins to bind to the estradiol-stimulated receptor and diminished their rate of uptake by the perfused liver of estrogen-treated rats, just as it did in normal rats. The current data indicate that under the influence of pharmacologic doses of estradiol the liver of the rat contains increased amounts of a functional lipoprotein receptor that binds lipoproteins containing apoproteins B and E. This hepatic lipoprotein receptor appears to mediate the uptake and degradation of lipoproteins by the normal liver as well as the liver of estradiol-treated rats. The hepatic receptor bears a close functional resemblance to the LDL receptor previously characterized on extrahepatic cells.     

The serum lipoprotein pattern of water buffalo (Bubalus bubalis)

1. The serum lipoprotein pattern of water buffalo was studied by means of electrophoresis and the lipoproteins were isolated by ultracentrifugation on the basis of their hydrated density. 2. High density lipoproteins (HDL) showed a higher level of cholesterol than did the other lipoproteins. Moreover, the level of phospholipids was higher in HDL than in very low density lipoproteins (VLDL). 3. The buffalo B100 apoprotein was similar to that of man and rat. Three apoproteins similar to human apo E, apo AI and AII were found in buffalo HDL, buffalo VLDL contained essentially apo B protein.     

The characterization of lipoproteins in the high density fraction obtained from patients with familial lecithin:cholesterol acyltransferase deficiency and their interaction with cultured human fibroblasts

Lipoproteins of density 1.063--1.21 g/ml were isolated from the plasma of three sisters of Irish origin with familial LCAT deficiency. Fractionation of the lipoproteins on the basis of particle size by chromatography on Sephacryl S-300 permitted partial separation of two major and at least three other minor components which differed in their lipid:protein ratio and their apolipoprotein content. One of the major components was a small spherical lipoprotein whose sole apolipoprotein was apoA-I; the second major component contained predominantly apoA-I, together with apoE, and in addition, an apolipoprotein of molecular weight 46,000 that was not cleaved by reduction of disulfide bonds, and which was identified as apoA-IV. This apoprotein has not previously been detected in the lipoproteins of LCAT-deficient patients. A second apoE-containing lipoprotein, which contained apoA-I and apoE in a ratio of approximately 2:1, was also present as a minor component, together with two or more minor components whose apoproteins were comprised of apoA-I and apoC. The apoE-containing lipoproteins competed efficiently with 125I-labeled LDL for binding to high affinity LDL-receptor sites on the surface of cultured human skin fibroblasts. The ability to bind to the LDL-receptor was directly proportional to the apoE content of the lipoproteins, even when other apoproteins, with the exception of apoB, were present in relatively large proportions. ApoE-containing 125I-labeled lipoproteins from an LCAT-deficient subject were also taken up and degraded by the cultured cells.     

Characterization of the plasma lipoproteins of the genetically obese hyperlipoproteinemic Zucker fatty rat

The plasma lipoproteins of the Zucker fatty rat were characterized with respect to lipid and apoprotein composition, and results were compared with those obtained from lean controls. Information on apoproteins was obtained from gel filtration experiments and electrophoresis on polyacrylamide gels. Very low density lipoproteins (VLDL) were increased several-fold in fatties, and 78% of their mass was triglycerides compared with 60% in the controls. Low density (LDL) and high density (HDL) lipoproteins were increased by a factor of 2, although their compositions were similar to those of the controls. Levels of apoVLDL, apoLDL, and apoHDL were five, two and two times higher, respectively, in the fatties, and the two most rapidly moving subunit peptides on polyacrylamide gels were disproportionately elevated in the apoproteins. The slower of these two bands was present in relatively greater amounts than the faster one in fatties. If the slower peptide is an activator of lipoprotein lipase, analogous to the comparable subunit peptides of human apolipoproteins, plasmas of fatties could contain up to 10 times more lipase activator activity than control plasma. This finding, and the fact that adipose tissue lipoprotein lipase activity of fatties was about 150% of controls, suggests that fatties have increased capacities for VLDL catabolism. We have previously shown that hepatic VLDL secretory rates are higher than normal in these animals. The increased capacity for catabolism may be a response to the altered secretory rates.     

Comparative molecular properties of swine and human very low density lipoproteins-apoproteins E and C

1. By means of 2-dimensional gradient-gel electrophoresis, the very low density lipoproteins (VLDL) apoproteins E and C profiles from human and swine plasma were studied. 2. The molecular properties (isoelectric point and molecular weight) of the VLDL apoproteins and their isoforms were determined and showed many similarities between species. 3. It also appears evident that a previously unrecognized apoprotein (C-III) and several associated isoforms may exist in swine; however, it's mobility on 2-dimensional gradient gels is very similar to Apo C-II.     

Characterization of plasma lipoproteins of grain- and cholesterol-fed White Carneau and Show Racer pigeons

Plasma cholesterol concentrations from White Carneau (WC) and Show Racer (SR) pigeons consuming a cholesterol-free grain diet averaged about 300 mg/dl, approximately 200 mg/dl as high density lipoproteins (HDL) and the remainder as low density lipoproteins (LDL). Consumption of a cholesterol-containing diet increased plasma cholesterol concentrations in both breeds to greater than 2000 mg/dl. Approximately one-half of this increase was as LDL with the remainder as beta-migrating very low density lipoproteins (beta-VLDL). There was little change in HDL concentration. LDL from cholesterol-fed animals had a greater net negative charge than control LDL, and was larger (Mr = 10 X 10(6) vs 3.2 X 10(60)) due to an increase in the number of cholesteryl ester molecules per particle. The principal apoprotein of LDL was apoB-100 with smaller amounts of apoA-I and several minor unidentified apoproteins. beta-VLDL was cholesteryl ester-rich, could be separated into two size populations by gel chromatography, and contained apoB-100 as its principal apoprotein. Apoprotein E was not detected in any of the plasma lipoproteins. HDL from control and cholesterol-fed animals was composed of a single class of particles with virtually identical composition resembling HDL2. The major apoprotein of HDL was apoA-I. There were no consistent quantitative or qualitative differences in the lipoproteins of the two breeds of pigeons that could help to explain the susceptibility to atherosclerosis of the WC or the resistance of the SR.     

Changes in the concentration of plasma lipoproteins and apoproteins following the administration of Triton WR 1339 to rats.

Changes in whole plasma and lipoprotien apoprotein concentrations were determined after a single injection of Triton WR 1339 into rats. Concentrations of apoproteins A-I (an activator of lecithin:cholesterol acyl transferase), arginine-rich apoprotein (ARP), and B apoprotein were measured by electroimmunoassay. The content of C-II apoprotein (an activaor of lipoprotein lipase) was estimated by the ability of plasma and lipoprotein fractions to promote hydrolysis of triglyceride in the presence of cow's milk lipase and also by isoelectric focusing on polyacrylamide gels. Apoproteins C-II and A-I were rapidly removed from high density lipoprotein (HDL) after Triton treatment and were recovered in the d 1.21 g/ml infranate fraction. A-I was then totally cleared from the plasma within 10--20 hr after injection. Arginine-rich apoprotein was removed from HDL and also partially cleared from the plasma. The rise in very low density lipoprotein (vldl) apoprotein that followed the removal of apoproteins from HDL was mostly antributed to the B apoprotein, although corresponding smaller increases were observed in VLDL ARP and C apoproteins. The triglyceride:cholesterol, triglyceride:protein, and B:C apoprotein ratios of VLDL more closely resembled nascent rather than plasma VLDL 10 hr after Triton injection. These studies suggest that the detergent may achieve its hyperlipidemic effct by disrupting HDL and thus removing the A-I and C-II proteins from a normal activating environment compirsing VLDL, HDL, and the enzymes. The possible involvement of intact HDL in VLDL catabolism is discussed in relation to other recent reports which also suggest that abnormalities of the VLDL-LDL system may be due to the absence of normal HDL.     

Cortisol, adrenocorticotropic hormone and apolipoprotein synthesis in rat hepatocytes]

The influence of cortisol (5 mg/kg body wt administered daily for 5 and 10 days) on biosynthesis of apoproteins of lipoproteins of very low density in the liver and on the synthesis of apolipoproteins of very low, low, and high density (VLDL, LDL, and HDL apoproteins, respectively) in the blood serum of adrenalectomized animals, and after replacement cortisol therapy was studied. Cortisol treatment during these periods resulted in the VLDL apoproteins biosynthesis inhibition in the rat liver. The synthesis of apolipoproteins was increased by adrenalectomy; this effect was eliminated after replacement cortisol treatment. The apoprotein synthesis was stimulated within 5 hours by single injection of cortisol or ACTH. Study of the blood serum apolipoproteins specific radioactivity indicated metabolic change of lipoproteins, such as disturbed conversion from VLDL to LDL. Single and prolonged cortisol administration led to the opposite results. The authors believe that the metabolic disturbances of lipoproteins in the blood play a more important role in the pathogenesis of cortisol-induced hyperlipidemia than lipoprotein syntesis stimulation in the liver.