Cholesteryl ester and triacylglycerol fatty acids in type V hyperlipidemia

The fatty acid compositions of plasma cholesteryl esters (CE) and triacylglycerols (TG) from seven healthy individuals and five patients with type V hyperlipoproteinemia were determined. Very low density (VLDL), low density (LDL) and high density lipoproteins (HDL) were isolated. The lipids were extracted from the lipoproteins and the triacylglycerols and cholesteryl esters separated for analysis. The fatty acid compositions of triacylglycerols from healthy and type V individuals were very similar. The cholesteryl esters from type V patients had increased contents of palmitic and decreased amounts of linoleic and arachidonic acids as compared to the normal individuals. The fatty acid composition of the cholesteryl esters from the high density lipoproteins had the greatest deviation. The fatty acid compositions of the triacylglycerols from the two groups were similar. However, the triacylglycerols in all lipoprotein fractions contained more palmitic and oleic and less linoleic and arachidonic acids than the cholesteryl esters.     

Plasma and lipoprotein fatty acid composition in glycogen storage disease type I

Nocturnal intragastric feeding has been shown to be an effective means to improve clinical and biochemical features in glycogen storage disease type I (GSD-I). In this study, we investigated the fatty acid patterns in a whole plasma and in circulating lipoproteins in patients on this therapy. The results demonstrated massive concentration of total fatty acids coupled with higher levels of triglycerides, free cholesterol, cholesterol ester and phospholipids. This hyperlipidemia involved all fatty acids without distinction of carbon or bond numbers. However, the increase was more pronounced for saturated than polyunsaturated fatty acids, as was demonstrated by the ratios of both oleic acid to linoleic acid (1.91±0.40 vs 0.80±0.09 in controls) and of ω3+ω6 to ω9 fatty acid families (0.92±0.11 vs 1.66±0.08 in controls). The fatty acid patterns in very low (VLDL), low (LDL) and high (HDL) density lipoprotein showed substantial differences in composition, reflecting an association between an abnormal lipoprotein pattern and essential fatty acid deficiency. Furthermore, GSD-I patients exhibited a significant increase in VLDL (17±2 vs 47±7 mg/dl) and LDL cholesterol (124±7 vs 206±24 mg/dl), coupled with a decrease in HDL cholesterol (49±4 vs 28±3 mg/dl). These data documenting high LDL cholesterol and low HDL cholesterol associated with an increased concentration and proportion of saturated fatty acids suggest that GSD-I patients on nocturnal intragastric feeding are at high risk for atherosclerosis and its complications.     

Eicosenoic and docosenoic acid incorporation in serum lipoproteins in rats fed rapeseed oil

Rats were fed rapeseed oil rich in eicosenoic (20∶1) and docosenoic (22∶1) acids for 7 days, and the fatty acid composition of the lipid classes of serum and serum lipoproteins was determined. Concentrations of 20∶1 and 22∶1 acids in the lipid classes were variable, especially among lipoproteins, and were a direct function of the alimentary state of the animal. The results suggest differences in the incorporation of the above acids among the major lipoprotein types and various lipid classes within a given lipoprotein type. The quick partial disappearance of very low density lipoproteins (VLDL) and of low density lipoproteins (LDL) containing 20∶1 and 22∶1 acids upon starvation and the preferential incorporation of these acids in the triacylglycerols of high density lipoproteins (HDL) are discussed.     

Net lipid transfer between lipoproteins in fish-eye disease plasma supplemented with normal high density lipoproteins

Native fish-eye disease plasma, which is deficient of both high density lipoproteins (HDL) and lecithin-cholesterol acyltransferase activity (α-LCAT), processing the free cholesterol of these lipoproteins, has been supplemented with normal isolated HDL₂ or HDL₃ and incubated in vitro at 37 C. After incubation for 0,7.5 and 24 hr the very low density (VLDL) and low density (LDL) lipoproteins as well as HDL were isolated, and their contents of triglycerides, phospholipids and free, esterified and total cholesterol were quantified. The resulting net mass transfer of the different lipids revealed a functioning transfer of cholesteryl esters and all other analyzed lipids between the lipoproteins, although no de novo esterification of the HDL cholesterol by LCAT in this plasma occurred. In accordance with previous findings there was a functioning esterification process of the free cholesterol of the combined VLDL and LDL of fish-eye disease plasma. The present results make it reasonable to conclude that the lack of HDL cholesterol esterification in this disease is not a result of a deficiency of cholesteryl ester transfer or lipid transfer activities.     

Lipoprotein lipid and protein synthesis in experimental nephrosis and plasmapheresis. I: Studies in rat in vivo

The incorporation of L-4,5-[³H]leucine into the ultracentrifugally separated apolipoproteins of very low, low, and high density lipoproteins (VLDL, LDL, HDL) and into serum albumin was found three-to four-fold higher in nephrotic than in normal rats one hour after intravenous injection. Incorporation of leucine into the circulating lipids was negligible. Increases of similar magnitude were obtained in the incorporation of simultaneously injected 1,5[¹⁴C] citrate into the lipids of VLDL, LDL, and HDL of nephrotic rats. Of the citrate carbons incorporated into serum and liver lipids, the proportion in cholesterol was higher in nephrotic rats when compared to normal rats. The incorporation of both precursors into total proteins and lipids of the liver vs. the incorporation into the lipoproteins was relatively lower in nephrotic than in control rats, indicating a preferential channeling into secretable products. The occurrence of enhanced new lipid synthesis in nephrosis was corroborated by the finding of markedly enhanced synthesis of lipoprotein-borne fatty acids and cholesterol from³H₂O. These results point out that while leucine is not an efficient in vivo precursor of lipoprotein lipids in nephrosis, de novo lipogenesis proceeds from other precursors. Similar trend of changes, though of smaller magnitude, was elicited in rats after double plasmapheresis, 18 hr apart, when measured 3 hr after the second plasma withdrawal. This indicates that the loss of circulating proteins either by direct removal or through kidney lesion stimulates the compensatory hepatic response involving excessive lipoprotein synthesis. Time-course studies showed that peak incorporation of leucine and citrate into the protein and lipid components of lipoproteins, respectively, as well as into serum albumin, occurred coincidentally 3 hr after the second plasmapheresis, suggesting an interdependence of the enhanced protein and lipid synthesis.     

Comparative hypocholesterolemic effects of capybara (Hydrochoerus hydrochaeris dabbenei) oil, horse oil, and sardine oil in cholesterol-fed rats

The hypocholesterolemic efficacy of various polyunsaturated fatty acids was compared in rats given cholesterol-enriched diets. Capybara oil (CO, linoleic+α-linolenic acids), horse oil (HO, α-linolenic acid), and sardine oil (SO, eicosapentaenoic+docosahexaenoic acids) were added to diets at 50 g/kg. The weight gain, food intake, and liver weight in the CO-fed group were significantly higher than those in other groups during the 6-wk experimental period. The serum total and very low density lipoprotein (VLDL)+intermediate density lipoprotein (IDL)+low density lipoprotein (LDL) cholesterol concentrations of the CO-fed and SO-fed groups were significantly lower than in the HO-fed group after 6 wk. The serum high density lipoprotein cholesterol concentration in the SO-fed group was significantly higher than that in the CO-fed and HO-fed groups. The fecal neutral sterol concentration in the CO-fed group was reduced significantly compared with the other groups, and the fecal bile acid concentration in the HO-fed group was significantly higher than that in the SO-fed group. The results of this study demonstrate that CO lowers the serum total cholesterol and VLDL+IDL+LDL-cholesterol concentrations in the presence of excess cholesterol in the diet as well as SO.     

Serum lipoprotein and apoprotein concentrations in 4-(4-chlorophenyl)-2-hydroxytetronic acid and clofibrate-treated cholesterol and cholic acid-fed rats

Influence of clofibrate and an aci-reductone, 4-(4-chlorophenyl)-2-hydroxytetronic acid (CHTA) on lipoproteins and apoproteins was studied in cholesterol- plus cholic acid-fed rats. CHTA (0.4 mmol/kg body wt, twice daily) significantly lowered serum total cholesterol and triglyceride concentrations at both 10 and 16 days, whereas clofibrate at the same dose did not alter serum cholesterol levels, but elevated serum triglyceride concentrations at 16 days. The abnormal cholesterol-rich very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL) and low density lipoproteins (LDL) produced by cholesterol plus cholic acid were significantly reduced in their cholesterol content by treatment with CHTA, a compound having an oxidation reduction potential. Conversely, clofibrate administration increased VLDL-cholesterol with concomitant decreases in IDL- and LDL-cholesterol concentrations. Administration of CHTA to cholesterol- plus cholic acid-fed rats significantly increased concentrations of VLDL and IDL, but had no effect on HDL protein. Both CHTA and clofibrate administration to cholesterol- plus cholic acid-fed rats significantly lowered IDL protein concentrations. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) studies of apoproteins revealed that clofibrate treatment significantly reduced apoC-III and C-II in VLDL, C-II in IDL, and apoA-IV and A-I in HDL. Rats treated with CHTA significantly raised apoC-II and C-III in HDL. Isoelectric focusing (IEF) of VLDL apoproteins showed a significant decrease in apoC-II, C-III-0 and apoC-III-3 in clofibrate-treated animals. Thus, the mechanism for antilipidemic action of the oxidation reduction compound, CHTA, which differs markedly from the prototype drug, clofibrate, is independent from major apoprotein modification.     

l-Carnitine effects on chemical composition of plasma lipoproteins of rabbits fed with normal and high cholesterol diets

l-Carnitine plays an important role in the mitochondrial uptake of long-chain fatty acids in mammals. It has recently been shown that this compound has a marked hypo-cholesterolemic effect when used in conjunction with lipid-rich diets. The aim of this study was to investigate the effects of l-carnitine on the fatty acid composition of plasma lipoproteins in rabbits fed with different diets. Four different groups were investigated: group I (standard diet), group II (standard diet supplemented with l-carnitine at 80 mg/kg), group III (standard diet supplemented with 0.5% cholesterol), and group IV (standard diet supplemented with 0.5% cholesterol plus l-carnitine at 80 mg/kg). The feeding period was 126 d. Total plasma cholesterol was indistinguishable in groups I and II, but increased nearly 40-fold in group III. This increment was reduced by 50% in group IV. Correspondingly, total cholesterol content in lipoprotein fractions [very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL) separated by agarose gel chromatography was the same for groups I and II, while for animals fed a cholesterol-rich diet (III) total cholesterol in VLDL+LDL increased nearly 100-fold when compared with groups I and II but, again, the increment was reduced by 50% in group IV. In contrast, total cholesterol in HDL increased only fivefold for both groups III and IV when compared with groups I and II, indicating no effects of l-carnitine on this parameter. The reduction of total cholesterol in VLDL+LDL particles in animals fed a cholesterol-rich diet plus l-carnitine was associated with a marked decrease in the ratio of cholesteryl ester to free cholesterol and a dramatic increase in their phospholipid content; opposite effects were observed for HDL. l-Carnitine induced a marked decrease in the saturated to unsaturated C₁₆+C₁₈ fatty acid ratio in cholesteryl esters associated with VLDL and LDL from animals fed with both normal and cholesterol-rich diets. The opposite effect (a large increase in the saturated to unsaturated fatty acid ratio) was observed for both cholesteryl esters and phospholipids associated with HDL in animals fed with both diets. The results suggested that the hypocholesterolemic effects of l-carnitine could be associated with increased systemic breakdown of cholesteryl esters, a probable increase in reverse cholesterol transport, and the stabilization of a phospholipid-based structure of VLDL+LDL particles.     

Lipid metabolism and tissue composition in Atlantic salmon (Salmo salar L.)—Effects of capelin oil, palm oil, and oleic acid-enriched sunflower oil as dietary lipid sources

Triplicate groups of Atlantic salmon (Salmo salar L.) were fed four diets containing different oils as the sole lipid source, i.e., capelin oil, oleic acid-enriched sunflower oil, a 1∶1 (w/w) mixture of capelin oil and oleic acid-enriched sunflower oil, and palm oil (PO). The β-oxidation capacity, protein utilization, digestibility of dietary fatty acids and fatty acid composition of lipoproteins, plasma, liver, belly flap, red and white muscle were measured. Further, the lipid class and protein levels in the lipoproteins were analyzed. The different dietary fatty acid compositions did not significantly affect protein utilization or β-oxidation capacity in red muscle. The levels of total cholesterol, triacylglycerols, and protein in very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL), and plasma were not significantly affected by the dietary fatty acids. VLDL, LDL, and HDL fatty acid compositions were decreasingly affected by dietary fatty acid composition. Dietary fatty acid composition significantly affected both the relative fatty acid composition and the amount of fatty acids (mg fatty acid per g tissue, wet weight) in belly flap, liver, red and white muscle. Apparent digestibility of the fatty acids measured by adding yttrium oxide as inert marker, was significantly lower in fish fed the PO diet compared to the other three diets.     

Effect of protein depletion on the VLDL triacylglycerol secretion and apoprotein synthesis by the perfused liver from pregnant rats

The effect of protein depletion in the pregnant rat on the polyunsaturated fatty acid incorporation into very low density lipoproteins (VLDL) has been investigated. The apoprotein pattern of these particles was determined. In in vivo experiments the amounts of serum and liver triacylglycerol were determined. VLDL were isolated and their apo C concentration calculated. In in vitro experiments the radioactivity of [³H] leucine incorporated into VLDL apoproteins was measured. The results show that protein depletion during pregnancy promotes a drastic increase in serum and liver triacylglycerol. The VLDL isolated from these animals show an increase in the triacylglycerol/protein ratio and a decrease in their content of apo C. Meanwhile, a significant reduction in the [³H]leucine incorporation into apo C peptides by the perfused liver of protein depleted rats was detected. On the other hand, protein deprivation did not affect labeled linoleic and arachidonic acid incorporation into triacylglycerol of the newly secreted VLDL. Taking these results together, let us deduce that a defective VLDL is secreted by the liver of the protein depleted pregnant rats. The abnormal composition of these particles may influence its normal metabolism through their effects on lipoprotein lipase and this fact could affect the normal supply of polyunsaturated fatty acids to the fetus.     

Response of plasma lipids to dietary cholesterol and wine polyphenols in rats fed polyunsaturated fat diets

This experiment was designed to evaluate the effects of dietary red wine phenolic compounds (WP) and cholesterol on lipid oxidation and transport in rats. For 5 wk, weanling rats were fed polyunsaturated fat diets (n−6/n−3=6.4) supplemented or not supplemented with either 3 g/kg diet of cholesterol, 5 g/kg diet of WP, or both. The concentrations of triacylglycerols (TAG, P<0.01) and cholesterol (P<0.0002) were reduced in fasting plasma of rats fed cholesterol despite the cholesterol enrichment of very low density lipoprotein + low density lipoprotein (VLDL+LDL). The response was due to the much lower plasma concentration of high density lipoprotein (HDL) (−35%, P<0.0001). In contrast, TAG and cholesteryl ester (CE) accumulated in liver (+120 and +450%, respectively, P<0.0001). However, the cholesterol content of liver microsomes was not affected. Dietary cholesterol altered the distribution of fatty acids mainly by reducing the ratio of arachidonic acid to linoleic acid (P<0.0001) in plasma VLDL+LDL (−35%) and HDL (−42%) and in liver TAG (−42%), CE (−78%), and phospholipids (−28%). Dietary WP had little or no effect on these variables. On the other hand, dietary cholesterol lowered the α-tocopherol concentration in VLDL+LDL (−40%, P<0.003) and in microsomes (−60%, P<0.0001). In contrast, dietary WP increased the concentration in microsomes (+21%, P<0.0001), but had no effect on the concentration in VLDL+LDL. Cholesterol feeding decreased (P<0.006) whereas WP feeding increased (P<0.0001) the resistance of VLDL+LDL to copper-induced oxidation. The production of conjugated dienes after 25 h of oxidation ranged between 650 (WP without cholesterol) and 2,560 (cholesterol without WP) μmol/g VLDL+LDL protein. These findings show that dietary WP were absorbed at sufficient levels to contribute to the protection of polyunsaturated fatty acids in plasma and membranes. They could also reduce the consumption of α-tocopherol and endogenous antioxidants. The responses suggest that, in humans, these substances may be beneficial by reducing the deleterious effects of a dietary overload of cholesterol.     

Effects of dietary triglyceride on the properties and lipid composition of plasma lipoproteins: Acute experiments in rats fed safflower oil

Male rats were administered 1.5 ml safflower oil by gastric intubation 0, 4, and 8 hr after a 16 hr fast. Plasma, liver, and adipose tissue were collected 16 hr after the last fatty meal. Rats fasted for 16 hr served as controls. Following fat feeding, the fatty acid composition of the very low density lipoprotein, triglyceride, and hepatic triglyceride were similar, as were the percentages of 18:2 in the very low density lipoprotein and hepatic cholesteryl esters. The phospholipids of liver and plasma lipoproteins were similar in the control groups, except that more 16:0 was present in the plasma lipoproteins. After fat feeding, the plasma lipoproein phospholipids were enriched with 18:2 more than were the hepatic phospholipids. Furthermore, the percentage of 18:2 in phospholipid was much less than in triglyceride or cholesteryl esters. Clearly, esterified lipids of liver and plasma lipoproteins (very low density lipoprotein, low density lipoprotein, and high density lipoprotein), and to a lesser extent, adipose tissue, were enriched with 18:2 derived from dietary triglyceride fatty acid even 16 hr after the terminal meal. A major proportion of the very low density lipoprotein isolated by ultracentrifugation in zonal rotors from plasma of fat fed animals had a faster rate-zonal mobility than did the very low density lipoprotein isolated from plasma of control animals. The very low density lipoprotein isolated from plasma of fat fed rats contained fewer moles of phospholipids, cholesterol, and cholesteryl esters, relative to triglyceride than did the very low density lipoprotein from plasma of animals not receiving safflower oil. The molar ratio triglyceride:phospholipid:cholesterol:cholesterol esters in the very low denity lipoprotein was 100:42.0:22.1:44.5 in the control group and 100:35.4:17.8:19.5 in the fat fed animals. It is postulated that an important biochemical mechanism by which dietary triglyceride fatty acids consumed by the animal over a long period of time alter plasma concentrations of triglyceride, phospholipids, and cholesterol esters is the directive influence of plasma free fatty acid, derived from dietary triglyceride, on the secretion of very low density lipoprotein lipids by the liver.     

Effects of sex on formation and properties of plasma very low density lipoprotein in vivo

The concentration and composition of the very low density lipoprotein (VLDL) lipids and the behavior of the VLDL in a density gradient in the zonal ultracentrifuge were examined in plasma obtained from normal fed male and female rats before and after intravenous injection of Triton WR-1339. Concentration of lipids in plasma VLDL of female rats was about half that of male animals. Following injection with Triton WR-1339, the concentration of VLDL lipids was higher in female rats (triacylglycerol) or similar (phospholipid, cholesterol, and cholesteryl esters) in both sexes. Female rats secreted much more VLDL triacylglycerol into the plasma compartment than did the male animals under the same experimental conditions. No differences were observed in lipid composition of the VLDL or in the position of the VLDL in the zonal rotor after ultracentrifugation in a density gradient of the lipoprotein from plasma of normal male and female rats before treatment with the detergent. However, after treatment with Triton, a higher proportion of the VLDL particles isolated from plasma of female rats displayed a more rapid rate-zonal flotation in the ultracentrifuge than did the VLDL produced by the male. The VLDL secreted by female rats contained fewer moles of phospholipid and free sterol per mol triacylglycerol than did the VLDL secreted by male animals under identical experimental conditions. The molar ratio of free cholesterol: cholesteryl ester in the VLDL secreted after treatment with Triton increased in both male and female rats. Simultaneously, the content of arachidonic acid in phospholipid of VLDL increased with a concomitant decrease in cholesteryl ester. These changes in fatty acid composition suggest that the inhibitory effect of Triton on lecithin-cholesterol acyl transferase activity affects the exchange of lipids between VLDL and high density lipoprotein. It can be concluded from the data reported here that sex influences the concentration of plasma lipids in vivo and the output and properties of the VLDL. Presented in part at the 59th annual meeting of the Federation of American Societies for Experimental Biology, Atlantic City, NJ, April 1975 (1). Recipient of a Career Development Award from the U.S. Public Health Service, No. 1-K4-HL-70329.     

Hypolipidemic activity of the surfactants aminimides,and their effects on lipid metabolism of rodents

A series of short chain fatty acid derivatives of aminimides were shown to possess hypolipidemic activity in rats and mice. Most of the agents tested lowered both serum cholesterol and triglyceride levels by at least 30% in mice and were effective in hyperlipidemic induced mice. 1,1-Dimethyl-1-(2-hydroxypropyl)-amine mersitimide lowered serum cholesterol levels 41% and serum triglyceride levels 56% at 20 mg/kg/day I.P. after 16 days. The same agent was active orally when administered to rats with a 38% reduction in serum cholesterol and a 52% reduction in serum triglycerides after 14 days. The agents inhibited liver acetyl CoA synthetase, ATP dependent citrate lyase and phosphatidate phosphohydrolase activities in vitro and in vivo. Reduction of cholesterol, triglycerides, neutral lipids and phospholipid levels were noted in the livers of mice treated for 16 days. In rat studies, cholesterol, triglyceride and phospholipid levels were reduced in liver, small intestine and the feces after two weeks' dosing. The cholesterol content was reduced in the very low density lipoprotein (VLDL) and low density lipoprotein (LDL) fractions but elevated in the high density lipoproteins (HDL). Triglyceride levels were lowered in the VLDL, and neutral lipid levels were reduced in the chylomicron and VLDL fractions.     

Preparation of fatty acid methyl esters from lipoprotein and macrophage lipid subclasses on thin-layer plates

A simple, accurate, and fast procedure for quantitative analysis of fatty acids (FA) in simple lipid subclasses from different biological specimens is presented. Lipid extracts of isolated plasma lipoproteins (very low, low, and high density lipoproteins; VLDL, LDL, and HDL, respectively) and permanent J774 mouse macrophages were fractionated into lipid subclasses by thin-layer chromatography (TLC) on silica gel 60 plates. Bands comigrating with authentic lipid standards were scraped off under argon and subjected to direct,in situ transesterification with BF₃/MeOH in the presence of the TLC adsorbent. Fatty acid methyl esters were subsequently quantitated by capillary gas chromatography. A comparison of the FA content present in total lipid extracts and in lipid subclasses separated by TLC revealed recoveries ranging from 93 (J774 cell extracts) to 99.7% (LDL). The method described is applicable for the measurement of FA in individual lipid subclasses and was successfully applied to quantitatively analyze the FA composition of the phospholipid, triacylglycerol, and cholesteryl ester fraction derived from VLDL, LDL, and HDL. In J774 lipid extracts, the FA composition of the phospholipid-, monoacylglycerol-, diacylglycerol-, free fatty acid-, triacylglycerol-, and cholesteryl ester fraction was quantitated. In addition we have analyzed the time-dependent loss of the major HDL polyunsaturated fatty acids (18:2, 20:4) in the phospholipid and cholesteryl ester fraction during copper-dependent peroxidation of HDL. We have not encountered analytical problems concerning low FA recoveries from CE-rich lipid extracts as indicated by almost quantitative recoveries of FA in LDL, HDL, and J774 extracts.     

Effect of high doses of synthetic estrogen on lipid metabolism in castrated male rats

The mechanism by which high doses of estrogen influences lipid metabolism was studied with a microtubular blocking agent. Castrated male rats received oral injection daily for 14 days of 3 mg hexestrol in olive oil, or oil alone as controls. About half of the animals in each group were injected intraperitoneally with 4 mg/100 g body weight colchicine 3 hr before they were killed. Hexestrol treatment caused an accumulation of esterified cholesterol in the liver while it decreased those in serum. Triglyceride concentrations slightly decreased in the liver but were unaffected in serum. On polyacrylamide-gel disc electrophoresis, the peaks of high density lipoproteins (HDL) and low density lipoproteins (LDL) were decreased remarkably. Electron microsopic examination of hepatocytes revealed electron-lucent lipid droplets in the cytoplasm. After a colchicine treatment of the control animals, concentrations of esterified cholesterol and triglycerides markedly increased in the liver, while those in serum decreased. Electron microscopic examination of hepatocytes revealed numerous secretory vesicles filled with nascent VLDL. In hexestrol-treated animals, the colchicine treatment was associated with marked decreases in serumesterified cholesterol and triglyceride as seen in the controls. However, there were no further increases of esterified cholesterol in the liver, and the increase of triglycerides was slight. Electron microscopic examination showed less secretory droplets than in the controls. These data suggest that very low density lipoproteins (VLDL) synthesis in the liver of hexestrol treated rats was inhibited. An accumulation of esterified cholesterol with a marked decrease in serum could not be accounted for by the inhibition of lipoproteins secretion, but rather by their enhanced entry into the liver.     

Regulation of fatty acid biosynthesis in Ehrlich cells by ascites tumor plasma lipoproteins

Fatty acid biosynthesis in Ehrlich cells in vitro was reduced when very low density lipoproteins (VLDL) isolated from the ascites tumor plasma were added to the incubation medium. The degree of inhibition was dependent on the VLDL concentration. At the VLDL concentrations usually present in the ascites plasma, there was a 30% decrease in biosynthesis as measured by³H₂O incorporation into fatty acids. Analysis of the labeled fatty acids by gas liquid chromatography indicated that this decrease was due to a reduction in fatty acid de novo biosynthesis and that chain elongation actually was increased when VLDL were present. Although ascites plasma low- and high density lipoproteins also produced a concentration-dependent inhibition of fatty acid biosynthesis, their effects were much smaller than those of the VLDL. Studies employing VLDL and radioactive free fatty acids indicated that the cells took up and utilized fatty acids derived from these lipoproteins. When VLDL were present, labeled free fatty acid incorporation into cell phospholipids, cholesteryl esters, and CO₂ decreased, whereas its incorporation into the cell free fatty acid pool increased. By contrast, the cells incorporated only very small amounts of fatty acid from either low- or high density lipoproteins. This suggests that the VLDL exert their inhibitory effect on fatty acid synthesis by supplying exogenous fatty acids to the cells. Presented in part at the AOCS Spring Meeting, Dallas, April 1975.     

Effects of a (n−3) polyunsaturated fatty acid-deficient diet on profiles of serum vitellogenin and lipoprotein in vitellogenic trout (Salmo gairdneri)

During the 6 months of vitellogenesis, 3-year-old female trout (Salmo gairdneri) were fed either an enriched (E) or an (n−3) polyunsaturated fatty acid (PUFA)-deficient (D) diet; serum vitellogenin (VG) and lipoproteins (d<1.21 g/ml) were analyzed at the third month of vitellogenesis (September) and at ovulation (December). The serum content of high density lipoproteins (HDL), the major protein class, maintained a mean value of 1500 mg/dl at both stages and with both diets. On the contrary, very low density lipoproteins (VLDL) were 90% higher during vitellogenesis than at spawning time, whereas excess vitellogenin circulated at this period (6580 mg/dl serum with diet E). The diet deficient in (n−3) lowered serum vitellogenin content by 16% in September and by 26% in December. The degree of (n−3) PUFA incorporation moderately decreased in low density lipoproteins (LDL) and in HDL with the (n−3)-deficient diet. The effect was more pronounced for 20∶5. On the other hand, essential 22∶6 was incorporated into vitellogenin at the same rate in September as in December with diet E (23% and 25%, respectively), whereas after a 3-month deficiency, the percentage fell to 12%; this percentage rose again to 19% at spawning time. These findings show that, although stored (n−3) PUFA were not exhausted after a 6-month dietary deficiency, the incorporation of essential fatty acids (EFA) into vitellogenin during the early stages of oogenesis was low, suggesting changes in egg composition that may influence hatching.     

Influence of dietary egg and soybean phospholipids and triacylglycerols on human serum lipoproteins

Human serum lipid and lipoprotein concentrations and compositions were compared in ten healthy middle-aged men consuming phospholipids from egg or from soybean or triacylglycerol mixtures with fatty acid compositions similar to those of the phospholipids. All subjects followed each of the four treatments: egg phospholipids (EP), soybean phospholipids (SP), an oil of fatty acid composition similar to that of EP, and an oil similar in fatty acid composition to SP for six weeks with “wash-out” periods of similar duration between treatment periods. The phospholipids, 15 g/d, and the oils, 12 g/d, which contained approximately equivalent quantities of fatty acids were provided to the subjects in gelatin capsules and were taken before meals. Diet intake was monitored by three-day food records. Serum lipoproteins (L_p) were separated by ultracentrifugation into very low density lipoproteins, low density lipoproteins (LDL), high density lipoproteins (HDL)₂ and HDL₃. L_p fractions and whole serum were analyzed for triacylglycerols, cholesterol (CH), phospholipids (PL), and protein. HDL cholesterol was determined in while serum. Cholesteryl esters were determined in some L_p fractions. Lipid compositions of L_p were expressed in mmol/g protein. Apoprotein B was measured in whole serum and in LDL; apoprotein A-I in whole serum and in HDL₃. In whole serum, CH and PL were significantly lower after the SP compared to EP treatment periods. CH, but not PL, was lower after SPTG compared to EP. CH in HDL₂ was significantly higher after SP compared to SPTG. Also, PL in HDL₂ were significantly higher after SP compared to all other treatments and to baseline. Although human serum lipid responses to dietary phospholipids were generally the same as responses to ingested oils of comparable fatty acid composition, the data suggest the possibility that SP selectively increase HDL₂ cholesterol and phospholipids.     

Regulation of lung surfactant cholesterol metabolism by serum lipoproteins

The isolated perfused rat lung was used as an experimental model in the study of the lipoprotein regulation of surfactant cholesterol metabolism. Addition of low density lipoproteins (LDL) to the perfusion medium at a cholesterol concentration of 0.5 mM had no inhibitory effect on [1-¹⁴C]-acetate incorporation into cholesterol of either the surfactant or residual fractions. Increasing the concentration of cholesterol in the medium to 2.5 mM resulted in significant inhibition of incorporation into cholesterol of both fractions. A similar inhibition resulted when lungs were perfused with 2.5 mM cholesterol in the form of high density lipoproteins (HDL). No inhibition of fatty acid synthesis, measured as incorporation into cholesteryl esters, was observed. The rate of uptake by perfused lung of cholesterol from both high and low density lipoproteins was similar. Competitive binding studies with¹²⁵I-labeled lipoproteins indicated the existence of lung receptors for both classes of lipoprotein. The rate of uptake of the apoprotein moiety of low density lipoproteins was significantly greater than that of high density lipoproteins. These data suggest that lung cholesterol metabolism may be subject to regulation by both low and high density serum lipoproteins.