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.     

Diurnal variation of plasma methyl sterols and cholesterol in the rat: Relation to hepatic cholesterol synthesis

Free cholesterol of plasma low density lipoproteins (LDL) and high density lipoproteins (HDL) of the rat was high and that of plasma very low density lipoproteins (VLDL) was low during the dark period of the diurnal cycle. Variations in the esterified plasma sterols were inconsistent. Free methyl sterols were high in all lipoproteins during the dark phase. Simultaneously, the incorporation of¹⁴C-acetate into nonsaponifiable sterols and the concentrations of free methyl sterols and cholesterol in the liver were elevated.     

Composition and concentration of lipoproteins in the serum of normal rats and rats deficient in essential fatty acids

A comparison is made of the concentration and chemical composition of serum lipoproteins of normal rats and rats deficient in essential fatty acids. The concentration of very low density lipoproteins (VLDL) and of low density lipoproteins (LDL) in serum of deficient rats is about half that found in normal rats, but the concentration of high density lipoproteins (HDL) is higher than normal and they contain an increased amount of cholesterol esters. The proportion of cholesterol that is esterified is much greater than normal in the serum of deficient rats. The deficiency of essential fatty acids also appears to result in compensating changes occurring in the composition of serum lipoproteins. In both VLDL and LDL of deficient rats the proportion of protein is raised and that of phospholipid lowered compared to normal, while the proportions of trigly ceride and cholesterol esters are unchanged.     

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.     

The effect of dietary supplementation of cholesterol and its subsequent withdrawal on the liver lipids and serum lipoproteins of chickens

Two groups of male chickens were fed either a control diet (group N) containing a standard poultry ration admixed with 10% corn oil or a cholesterol diet (group C) in which the control diet was supplemented with 1% cholesterol. After 6 weeks on the diets, a negligible amount of very low density lipoprotein (VLDL) was found in the serum from control animals. On the other hand, the serum VLDL from the cholesterol-fed birds was the predominant lipoprotein and carried 72% of the total serum lipids. Surprisingly this lipoprotein from cholesterol-fed animals was very low in triglycrides (6%) and high in total cholesterol (77%). While the level of serum low density liporotein was unaffected by the ingestion of cholesterol, the concentration of total lipids and phospholipids in the high density lipoprotein decreased in cholesterol-fed animals. The greatest change in liver lipids from animals fed cholesterol was found in the cholesterol esters, whereas the unesterified cholesterol, triglyceride and phospholipid varied slightly or remained constant. In normal animals the distribution of cholesterol between the liver and the serum was about equal, whereas in the cholesterol-fed birds the liver accounted for 80% of the cholesterol found in the liver-serum pool. In order to determine how the hypercholesterolemic bird responds to the withdrawal of cholesterol from the ration, a diet-exchange experiment was conducted. In this study the birds that were originally fed the cholesterol diets (group C) for 6 weeks were placed on the control diet (group CN) and the birds fed the control diet (group N) for 6 weeks were given the cholesterol diet (group NC). At periodic intervals, 1, 3, 7 and 14 days following the change of diets, 3–5 animals from each group were sacrificed, and analyses performed on their serum lipoproteins and liver lipids. Within one day after the diet substitution, there was a 31-fold increase and a 46% decrease, respectively, in the serum VLDL concentration in groups NC and CN as compared with their corresponding steady state values (groups N and group C, respectively). The liver cholesterol increased 4-fold and decreased 40%, respectively, in the two groups NC and CN as compared with the values obtained before the diet substitution. It is suggested that the concentration of cholesterol in the liver is the principal factor controlling cholesterol metabolism in chickens fed a hypercholesterolemic diet. This represents a portion of a Ph.D. thesis submitted by A.W. Kruski to the University of Illinois in February 1971.     

Liver and serum lipids and lipoproteins of rats fed 5% L-lysine

Soybean protein and casein supplemented with 1% Arg were compared for their ability to prevent fatty livers caused by excess dietary Lys. The concentrations of serum lipids and lipoproteins of rats fed 5% Lys and having vatty livers were also compared with those of rats fed the identical diet but lacking fatty livers when killed. The total liver lipids, triglycerides and cholesterol of rats fed 15% casein +5% Lys were 3.9, 12.4 and 2 times control values, respectively. Rats fed 5% Lys +1% Arg or 5% Lys with 15% soybean protein had liver lipid concentrations similar to controls fed no supplemental Lys. Serum total lipids, triglycerides, cholesterol, phospholipids and free fatty acids also did not change, and serum ketone bodies were slightly elevated with Lys feeding whether the rats had fatty livers or not. The concentrations of circulating HDL were slightly depressed in all rats fed 5% Lys while LDL were significantly elevated, particularly in rats without fatty livers. Serum VLDL did not change with 5% dietary Lys. Overall, excessive dietary Lys caused fatty livers which were prevented by varying the diet or length of feeding. Excess Lys feeding altered lipoprotein metabolism shown by decreased serum HDL and a substantial elevation in LDL. The latter was more apparent when the fat accumulation in liver was less severe or absent. The data suggest that the fatty liver from Lys excess is probably unrelated to increased fat mobilization from storage, decreased fat oxidation or to a major block in the transport of triglycerides from the liver to the circulation.     

The distribution of dietary plant sterols in serum lipoproteins and liver subcellular fractions of rats

Rats were fed plant sterols containing campesterol and β-sitosterol in the different proportions, and their distribution in serum lipoproteins and in liver subcellular fractions was determined. In serum lipoproteins, the percentage as well as the concentration of plant sterols increased with the increase in the density of lipoproteins. Thus, high density lipoprotein (HDL) contained the highest and very low density lipoprotein (VLDL), the lowest. Also, there were distinct differences in the ratio of campesterol to sitosterol among lipoproteins, it was the highest in VLDL and lowest in HDL. Quantitatively, more than 75% of campesterol and 80% of sitosterol were carried in HDL; the values were significantly different from those of cholesterol (ca. 70%) in relation to total cholesterol. The distribution of plant sterols in liver subcellular fractions was virtually the same with that of cholesterol. Both nuclei and microsomes contained approximately 40% of total plant stetols. A preliminary part of the study was presented at the First Congress of the Federation of Asian and Oceanian Biochemists in Nagoya, October 1977.     

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.     

Increased amounts of cholesterol precursors in lipoproteins after ileal exclusion

Serum cholesterol precursor sterols reflect the activity of cholesterol synthesis. In this study, squalene, methyl sterol and lathosterol contents were studied in very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL) of heterozygous familial hypercholesterolemia patients without and with ileal bypass. The contents of lathosterol and all methyl sterols (lanosterol, Δ^8,24-dimethylsterol, Δ⁸-dimetylsterol, Δ⁸-methostenol and methostenol), but not of squalene were increased in all lipoproteins by ileal bypass. The increase in the free methyl sterols was more marked than that in the esterified ones. The percentage esterification of the methyl sterols was highest in HDL and lowest in VLDL. Lipoprotein methyl sterol contents were positively correlated with each other and with cholesterol synthesis. The methyl sterols were slightly concentrated in LDL, and squalene strongly concentrated in VLDL. It is concluded that long-term stimulation of cholesterol synthesis increases the methyl sterols in all lipoproteins.     

A micro‐method for lipoprotein cholesterol profiles: Impact of CETP in KKAy mice

The aim of the present study was to assess cholesterol‐containing lipoprotein profiles in minute serum samples. The lipoprotein profiles of KKA^y and transgenic KKA^y‐CETP mice and of other species were determined. The transgenic KKA^y‐CETP mice express the simian enzyme cholesteryl ester transfer protein (CETP). The serum profile of the cholesterol‐containing high‐density (HDL), low‐density (LDL) and very‐low‐density lipoproteins (VLDL) was monitored on a Superose 6 column using fast protein liquid chromatography. Serum from several mouse and rat strains, rabbit, hamster, pig and man was included for comparative and method validation purposes. The chromatograms showed that the transgenic KKA^y‐CETP mice had significantly decreased relative levels of HDL vs. VLDL and LDL cholesterol (p <0.001). Introduction of the CETP gene shifted the serum profile of the cholesterol‐containing lipoproteins of the KKA^y‐CETP mice closer to the human profile in a dose‐dependent manner, thus making these mice an interesting model for man. The described lipoprotein separation technology offers promising and reliable opportunities for studies of blood lipoprotein profiles with minute serum samples, in both animals and man.     

Induction of long-lasting hypercholesterolemia in the rat fed a cystine-enriched diet

The influence of dietary excess (5%) of L-cystine on rat plasma lipoproteins was examined. After only one week of cystine feeding, an increase in the plasma cholesterol level and a decrease in triglyceride levels were observed. The increase in cholesterol level became greater when the duration of cystine-enriched diet increased until eight weeks (+131% after eight weeks), but no further increase occurred between 8 and 20 weeks. This change was essentially due to the progressive increase in cholesterol levels in high density lipoproteins (HDL) and in lipoproteins isolated between 1.040 and 1.063 g/ml, i.e., certain low density lipoproteins (HDL₂), and containing mainly apoE-rich lipoproteins (HDL₁). The decrease in plasma triglycerides resulted from that of chylomicrons and very low density lipoproteins (VLDL). The effects observed after four or eight weeks of cystine feeding were maintained for eight weeks after replacing the cystine diet by the standard diet. Ingestion of the standard diet containing either cholestyramine (2%) or probucol (0.25%) following eight weeks of cystine feeding significantly decreased plasma cholesterol levels. It is concluded that cystine-fed rats are a useful tool of investigation for understanding mechanisms leading to increased plasma cholesterol level and for hypocholesterolemic drug trials.     

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.     

Dual action of neutral sphingomyelinase on rat hepatocytes: Activation of cholesteryl ester metabolism and biliary cholesterol secretion and inhibition of VLDL secretion

To address the role of cell membrane neutral sphingomyelinase (EC 3.1.4.12; SMase) in the regulation of cholesterol metabolism in the liver parenchymal cell, we examined the effect of exogenous neutral SMase on the metabolism of cholesteryl esters and the secretion of VLDL and biliary lipids in isolated rat hepatocytes. We show that treatment of hepatocytes with SMase (20 mU/mL) resulted in the intracellular buildup of cholesteryl esters, increased ACAT (EC 2.3.1.26) activity without affecting the ACAT2 mRNA level, and increased cytosolic and microsomal cholesteryl ester hydrolase (EC 3.1.1.13) activity. This was accompanied by increases in the secretion of biliary. bile acid, phospholipid, and cholesterol and in increased cholesterol 7α-hydroxylase (EC 1.14.13.17) activity and levels of mRNA, as well as decreased levels of apoB mRNA and a decreased secretion of VLDL apoB (apoB-48, ∼45%; apoB-100, ∼32%) and lipids (∼55%). Moreover, the VLDL particles secreted had an abnormal size and lipid composition; they were larger than controls, were relatively enriched in cholesteryl ester, and depleted in TG and cholesterol. Cell-permeable ceramides did not replicate any of the reported effects. These findings demonstrate that the increased cholesteryl ester turnover, oversecretion of biliary cholesterol and bile acids, and undersecretion of VLDL cholesterol and particles are concerted responses of the primary hepatocytes to exogenous neutral SMase brought about by regulation at several levels. We suggest that plasma membrane neutral SMase may have a specific, ceramide-independent effect in the regulation of cholesterol out-put pathways in hepatocytes.     

Dietary squalene increases tissue sterols and fecal bile acids in the rat

Feeding 1% squalene increased markedly the concentrations of squalene and methyl sterols in each serum lipoprotein class, intestinal mucosa, liver and also in adipose tissue. It also increased cholesterol concentration of the liver and serum VLDL, and esterified cholesterol in serum LDL as well as fecal bile acids. The results suggest that absorbed dietary squalene contributes to some extent to the squalene content of adipose tissue, effectively increases the overall cholesterol synthesis and enhances cholesterol elimination preferentially as fecal bile acids.     

Effect of nicotine on lipoprotein metabolism in rats

Nicotine, a major component of cigarette smoke, plays an important role in the development of cardiovascular disease and lung cancer in smokers. The effect of nicotine on lipoprotein metabolism was studied using rats as the experimental animal. There was a significant increase in the total cholesterol, phospholipids, and triglycerides as well as the amount of lipids associated with very low density lipoprotein (VLDL) and low density lipoprotein (LDL) in sera of nicotine-treated rats. The incorporation of ³H labeled leucine into the apo B was found to be increased both in the medium and associated cells in the hepatocytes isolated from nicotine-treated rats indicating an increased synthesis and secretion of the apo B containing lipoproteins. This was further confirmed by the higher incorporation of ¹⁴C acetate into total and individual lipids of LDL and VLDL secreted into the medium as well as that associated with different lipids in the cell layer. The activity of lipoprotein lipase in extrahepatic tissues and plasma lecithin cholesterol acyltransferase activity were significantly lower in nicotine-treated rats. These results indicate that nicotine exerts hyperlipidemic effects particularly by increasing the synthesis and secretion of triglyceride-rich lipoproteins. Since nicotine is one of the major hazardous components present in cigarette smoke and tobacco, one can extrapolate that the deleterious effect exerted by nicotine on rats extends to cigarette smokers and those who use other forms of tobacco.     

Serum lipid transport systems: Recent advances

Lipids circulating in the plasma are transported in water soluble form as lipid-protein complexes. Lipoproteins can be classified according to size, density, electrophoretic mobility and protein composition. The ability of low density lipoproteins and very low density lipoproteins (VLDL) to form complexes with different polyanions has been also used as a method for separation and study of serum lipoproteins. Even within classes of lipoproteins closely related otherwise, the amount of different lipids and their ratios to each other and to protein are variable. Two enzymatic systems seem to be at least partly responsible for the different lipid compositions of serum lipoproteins: lipoprotein lipase and lecithin-cholesterol acyltransferase (LCAT). LCAT, which seems to be associated with α-lipoproteins, is responsible for the formation of the bulk of cholesteryl-esters in human serum. Changes in activity of this enzyme may explain the observed changes with age and disease of serum cholesteryl-ester fatty acids (CEFA). Differences in CEFA pattern are found between newborn and adult animals, including man. The activity of serum LCAT was observed to increase with age in animals and to decrease markedly in patients with liver cirrhosis. These patients show abnormal serum CEFA patterns and abnormally low proportions of pre-β- (VLDL) and α- (high density) lipoproteins. One of five papers to be published from the Symposium “Lipid Transport” presented at the AOCS Meeting, New Orleans, April 1970.     

Plasma lipoproteins in dairy cows with naturally occurring severe fatty liver: Evidence of alteration in the distribution of apo A-I-containing lipoproteins

The relationships between fatty liver in dairy cows and reduced levels of plasma lipoproteins, and particularly of low density lipoproteins (LDL), has been previously described. Since electrophoretic heterogeneity of ultracentrifugally isolated LDL (d, 1.006–1.063 g/ml) has been found, the exact nature of this reduction in cows with fatty liver was investigated. Lipoproteins from control and severely afflicted animals were isolated by ultracentrifugation and affinity chromatography on heparin-Sepharose CL 6 B. Gradient gel electrophoresis of lipoproteins on 4–30% gels and an immunolocalization study of apoprotein A-I (apo A-I) showed that control animals have two subpopulations of apo A-I-containing particles with a mean radius of 6.52 and 5.05 nm. In the fatty liver cows, the former was clearly shifted toward smaller particles. We concluded that the depressed level and compositional modifications of LDL in severe fatty liver cows result from a decrease in the oversized apo A-I-containing lipoproteins which can be isolated in the LDL density range. This could stem from the decreased supply of triglyceride-rich lipoprotein surface components for the production of these lipoproteins. The modifications can be plausibly explained by a reduced synthesis or secretion of very low density lipoproteins (VLDL) by the liver.     

Serum lipoprotein hydrolysis by purified lipases

Purified lipases from pork pancreas,Rhizopus arrhizus andLeptospira biflexa hydrolyze the triglycerides of pork very low density lipoproteins (VLDL), while higher density lipoproteins are not affected significantly. The velocity versus substrate curves for the VLDL were sigmoid.     

Effect of dietary fat supplementation on the composition and positional distribution of fatty acids in ruminant and porcine glycerides

Dietary fats which were protected from ruminal metabolism were fed to ruminants, and the constituent fatty acids subsequently appeared in the glycerides of tissues and secretory products. These dietary fat induced alterations in tissue lipid composition were particularly apparent when the fat source was enriched with linoleic acid. Similarly, when pigs were fed linoleic-enriched fats, the linoleic acid was incorporated into the adipose tissue triglycerides. Stereospecific analyses were carried out on triglycerides from various tissues and secretory products obtained from animals fed control or linoleate-enriched diets. The analysis of adipose tissue triglycerides showed that linoleate and oleate were preferentially esterified to positions 2 and 3 (cattle and sheep), and positions 1 and 3 (pigs). Of the other major adipose tissue fatty acids, palmitate was preferentially esterified at position 1 (ruminants) and position 2 (pigs), and stearate was preferentially esterified at positions 1 and 3 (ruminants), and position 1 (pigs). Stereospecific analysis of high mol wt milk triglycerides showed that linoleate was either evenly distributed on all three positions (goats), or predominantly on position 3 (cows). Furthermore, the incorporation of this linoleate did not markedly alter the positional specificity of the other major milk triglyceride fatty acids. Of these fatty acids, the short and medium chain length acids (butyratelaurate) were mainly on position 3, myristate and palmitate on positions 1 and 2, and stearate and oleate evenly distributed. Thoracic duct lymph triglycerides from sheep tended to show preferential incorporation of linoleate at position 3, palmitate at position 2, and stearate at position 1 and 3; oleate, on the other hand, tended to be evenly distributed on all three positions of the lymph triglyceride. The stereospecific arrangement of fatty acids in sheep liver triglycerides was similar to that of lymph triglycerides, and this may reflect the uptake of intact or partially hydrolysed chylomicron and/or very low density lipoprotein triglycerides by the liver. There were also some analogies in the stereospecific arrangement of fatty acids on ruminant lymph and milk triglycerides and this may reflect an incomplete hydrolysis of chylomicron and/or very low density lipoprotein triglycerides prior to uptake by the mammary gland. An unusual feature of lymph from sheep fed linoleate was the presence of phospholipids which contained large amounts of linoleate in ca. equal proportion at both positions 1 and 2 of the phospholipid molecule.     

Trübungsmessung von Lipoproteinen nach Polyanionen-Präzipitation auf dem Autoanalyzer

Turbidity Measurement of Lipoproteins after Polyanion Precipitation in the Autoanalyzer A new method for the diagnosis of fat metabolism disorders is given. Using this method, hyperlipemia are detected by turbidity measurement after selective precipitation of lipoproteins in serum with the aid of polyanions. A comparison of the turbidity measurement with the determination of triglycerides and cholesterol gave a good agreement with a correlation of 95%. Furthermore, it was found that different types of hyperlipemia with increased levels of VLDL and LDL or HDL can be distinguished by selective precipitation of VLDL and LDL with heparine and MgCl₂, and of all the lipoproteins with dextrane sulfate and CaCl₂, respectively.