Cholesterol In Rat Liver Research Articles

Oat Bran, Barley and Malted Barley Lower Plasma Cholesterol Relative to Wheat Bran but Differ in Their Effects on Liver Cholesterol in Rats Fed Diets with and without Cholesterol

Males rats were fed diets containing wheat bran, oat bran, barley or malted barley without or with 10 g/kg cholesterol + 1 g/kg cholic acid (referred to as "cholesterol"). Plasma total, HDL, and VLDL+LDL cholesterol concentrations were higher overall in rats fed cholesterol. There was a significant interaction between dietary cholesterol and cereal type. Higher concentrations of total and VLDL+LDL cholesterol were found in rats fed cholesterol with wheat bran than in those fed oat bran, barley or malted barley. HDL cholesterol concentrations were higher overall in rats fed wheat bran than in those fed oat bran or barley but not malted barley. Liver cholesterol pools were higher overall in rats fed cholesterol. In all animals fed oat bran, liver cholesterol was lower than in rats fed barley or malted barley. Hepatic HDL receptor activity was lower overall in rats fed cholesterol. There was no independent effect of cereal type on HDL receptor activity, but there was a significant interaction with dietary cholesterol. Activity tended to be higher in rats fed malted barley with cholesterol than in rats fed malted barley without cholesterol. LDL receptor activity was not affected by cereal type but was significantly lower overall in rats fed cholesterol.

Effect of dietary fish, corn and palm oils on rat liver cholesterol and cholesteryl esters and plasma lipoproteins

Effect of dietary fish, corn and palm oils on rat liver cholesterol and cholesteryl esters and plasma lipoproteins

7α Hydroxylation of 25‐Hydroxycholesterol in Liver Microsomes

Rat, pig and human liver microsomes were found to catalyze 7 alpha-hydroxylation of 25-hydroxycholesterol. In contrast to cholesterol 7 alpha-hydroxylase activity, the 7 alpha-hydroxylase activity towards 25-hydroxycholesterol in rat liver was not stimulated by cholestyramine treatment. After transfection with cDNA for human cholesterol 7 alpha-hydroxylase, COS cells showed a significant activity towards cholesterol but not towards 25-hydroxycholesterol. During purification of cholesterol 7 alpha-hydroxylase from pig liver microsomes, about 99% of the 7 alpha-hydroxylase activity towards 25-hydroxycholesterol and 27-hydroxycholesterol was clearly separated from 7 alpha-hydroxylase activity for cholesterol. The small amount of 25-hydroxycholesterol 7 alpha-hydroxylase activity retained in a partially purified preparation of cholesterol 7 alpha-hydroxylase was not inhibited by addition of cholesterol, indicating that the oxysterol binding site is different from the cholesterol binding site, presumely due to the presence of two different enzymes. It is concluded that different enzymes are involved in 7 alpha-hydroxylation of cholesterol and 7 alpha hydroxylation of side-chain-oxidized cholesterol in rat, pig and human liver. Inhibition experiments with a partially purified fraction of the oxysterol 7 alpha-hydroxylase from pig liver gave results consistent with the contention that the same enzyme is responsible for 7 alpha hydroxylation of both 25-hydroxycholesterol and 27-hydroxycholesterol. It has been suggested that cholesterol 7 alpha-hydroxylase can preferentially use oxysterols, in particular 25-hydroxycholesterol, as substrates and by this means inactivate important physiological regulators of cholesterol homeostasis. Such a mechanism would explain the unique property of the liver to resist down-regulation of the low-density-lipoprotein receptor [Dueland, S., Trawick, J.D., & Davies, R.A. (1993) J. Biol. Chem. 267, 22695-22698]. The present results do not support the contention that the important coupling between cholesterol 7 alpha-hydroxylase activity, the low-density-lipoprotein receptor activity and hydroxymethylglutaryl coenzyme A reductase activity in liver cells is due to inactivation of 25-hydroxycholesterol or 27-hydroxycholesterol by the action of cholesterol 7 alpha-hydroxylase.

Prune Fiber or Pectin Compared with Cellulose Lowers Plasma and Liver Lipids in Rats with Diet-Induced Hyperlipidemia

Previous research indicated that prunes in the diet of men with hypercholesterolemia lowered plasma and LDL cholesterol concentrations. To further study lipid metabolism in response to ingesting prunes, we conducted an animal study to test the hypotheses that fiber extracted from prunes, compared with purified cellulose, lowers plasma and liver cholesterol in rats with diet-induced hyperlipidemia and that the response is dose dependent. Rats were randomly assigned to one of five experimental diet groups. Four of the diets contained cholesterol and cholic acid to induce hyperlipidemia. The fiber source in the hyperlipidemic diets was 6% cellulose, 3% prune fiber, 6% prune fiber or 3% pectin. The fifth group, the nonhyperlipidemic control, was fed a diet containing 6% cellulose without cholesterol or cholic acid. Rats consumed one of the five diets ad libitum for 28 d, then were killed after 16 h without food. Plasma, LDL and liver cholesterol concentrations were higher in the hyperlipidemic control than the nonhyperlipidemic control and lower in the groups fed diets containing pectin or prune fiber than in the hyperlipidemic control group. No differences in plasma or liver cholesterol concentrations were detected between groups fed either dose level of prune fiber or between groups fed 6% prune fiber and pectin. These results indicate that fiber extracted from prunes lowers plasma and liver cholesterol in hyperlipidemic rats, although a dose-dependent response was not detected.

Effects of Casein and Soy Protein on Accumulation of Cholesterol and Dolichol in Rat Liver

A diet containing 15% (w/w) fat and 20% (w/w) of either casein (CAS) or soy protein (SOY) was fed to 4-week-old rats for a period of 18 months. The effects of these dietary proteins on the accumulation of cholesterol and dolichol in livers were studied. After 1 month, the amount of liver cholesterol was about 5 mg/g of liver. After an additional 5 months of feeding, there was a slight decrease in cholesterol per gram of liver (3.6 mg/g of liver in CAS-fed rats and 2.6 mg/g of liver in SOY-fed rats). However, after 18 months, there were a remarkable increase (7.5 mg/g of liver) in CAS-fed rats and only a slight increase in SOY-fed rats. The proportions of liver cholesterol ester in rats fed the CAS diet were 60-70% of the total cholesterol during the experimental period, but in the case of the SOY diet, only rats fed the diet for 1 month showed a high level, 70%, of cholesterol ester. The amounts of liver dolichol in rats fed the CAS and SOY diets after feeding for 18 months were 60 micrograms and 47 micrograms of liver, respectively. There was a 1.5-fold increase in both diets for a period of 18 months. The proportions of liver dolichyl fatty ester in rats fed the CAS diet were 35-40% of the total dolichol during the experimental period, but in the case of the SOY diet, only rats fed the diet for 1 month showed a high level, 36%, of dolichyl fatty ester. The proportions of dolichol ester in rats fed the SOY diet were 25-30% after 6 and 18 months of feeding. These observations indicated that the SOY diet depresses the accumulation of both liver dolichol and cholesterol.

Rice bran and wheat bran: selective effect on plasma and liver cholesterol in high-cholesterol fed rats

Plasma and liver cholesterol concentrations were measured in Sprague-Dawley rats fed high-cholesterol (1% w/w) semipurified diets containing various fibre sources (10% w/w) for 21 days. The dietary contents of fibre were constant among the diets, except for the control diet which was devoid of fibre source. Rice bran (either crude or parboiled) produced lower plasma LDL cholesterol concentrations than wheat bran. The content of liver cholesterol in rats fed rice bran diets was significantly lower than in rats fed the wheat bran diet. When comparing the compositions of the fibre sources, this study suggests that, apart from the polyunsaturated fatty acids of rice bran, the observed effects are mainly attributable to high soluble fibre content.

Comparative Effects of Dietary Palm Oil, Perilla Oil, and Soybean Oil on Lipid Profiles in Differently Aged Rats Fed on Hypercholesterolemic Diets.

The effects of palm oil, soybean oil, and perilla oil on the lipid profiles of liver and serum were compared in young (1 month old) and adult (8 months old) rats fed on hypercholesterolemic diets. In young rats, the concentration of serum cholesterol was highest in the order of palm oil (PAO), soybean oil (SBO), and perilla oil (PEO), whereas it was comparable among the groups of adult rats, resulting in an age-dependent increase in the rats fed on PEO. In young rats, but not in adult rats, the ratio of HDL-/total-cholesterol was significantly increased with an increase in the degree of unsaturation of dietary fats. Dietary PAO, when compared with SBO or PEO, prevented the accumulation of liver cholesterol in adult rats, when expressed as mg per liver. No fat-effect on liver cholesterol was seen in young rats. SBO amd PEO, when compared with PAO, markedly enhanced fecal output of bile acids in adult rats. The concentration of serum triacylglycerol showed a fat-dependent response, whereas that of liver triacylglycerol showed both an ageand fat-dependent response. Thus, PAO showed an effect similar to that of SBO on the serum cholesterol level in adult animals fed on a hypercholesterolemic diet.

Dietary Sucrose but not Starch Promotes Protein-Induced Differences in Rates of VLDL Secretion and Plasma Lipid Concentrations in Rats

Casein instead of soybean protein in a low fat, cholesterol-free diet containing sucrose increases both lipid secretion by rat liver and plasma cholesterol concentration. Male rats were studied to determine whether dietary sucrose is a prerequisite for these protein-induced differences of lipid metabolism in vivo. After 6 wk of consuming either casein plus sucrose, soybean protein isolate plus sucrose, casein plus starch or soybean protein isolate plus starch (carbohydrate, 69 g/100 g diet; protein, 20 g/100 g diet) plasma lipids were measured. VLDL degradation was blocked by Triton WR-1339 and rates of lipid secretion were calculated from the observed linear increase in plasma levels with time. Plasma cholesterol concentrations and rates of secretion of VLDL cholesterol and triglycerides were 27, 47 and 34% higher, respectively, in animals fed casein plus sucrose compared with soybean protein plus sucrose. These differences were clearly diminished or absent when starch was the dietary carbohydrate. The data substantiate the finding that dietary sucrose but not dietary starch promotes a casein-induced increase in hepatic cholesterol secretion and thus contributes to casein-induced hypercholesterolemia in rats. On the contrary, differences of triglyceride secretion were not reflected in different plasma lipid concentrations.

Changes in cholesterol accumulation and steroid excretion in response to cellulose, alfalfa or oats in cholesterol-fed rats

Experiments were conducted to investigate the mechanisms by which some sources of dietary fiber reduce accumulation of liver cholesterol in rats fed a cholesterol-containing diet. Male Wistar rats were fed a semipurified diet containing no fiber (sucrose replacing dietary fiber) or 15% cellulose, alfalfa or whole ground oats as a source of dietary fiber with a without 0.25% cholesterol added. Serum and liver cholesterol level, liver HMG CoA reductase activity, and fecal bile acid and neutral steroid excretion were measured after 21 days. Serum cholesterol levels were not different in any of the diet groups. In cholesterol-fed rats, alfalfa resulted in a reduction in the level of liver cholesterol accumulation in comparison to cellulose or the fiber-free diet but oats did not. Daily bile acid and neutral steroid excretion were increased in response to cholesterol feeding but little difference was observed among the groups fed the various dietary fiber sources except that alfalfa resulted in lower excretion rates compared to other fiber-containing diets. HMG CoA reductase activity was reduced by cholesterol feeding and was significantly increased in response to alfalfa in the absence of dietary cholesterol. The relative amounts of bile acids excreted was altered both by cholesterol feeding and by the source of dietary fiber. Cholesterol feeding resulted in an increase in the amount of chenodeoxycholic acid derivatives excreted, especially in the 6β-hydroxylated, muricholic acids. Dietary fiber appeared to increase the contribution of chenodeoxycholic and lithocholic acids to the resultant increase in response to dietary cholesterol. These changes in the relative amounts of bile acids excreted in response to this cholesterol challenge are suggested as a partial explanation of the reduction in accumulation of liver cholesterol in rats in response to dietary cholesterol.

Dietary Soluble Fiber and Cholesterol Affect Serum Cholesterol Concentration, Hepatic Portal Venous Short-Chain Fatty Acid Concentrations and Fecal Sterol Excretion in Rats

Sprague-Dawley rats were fed diets containing 7.5% dietary fiber as cellulose (control), pectin, psyllium or oat bran with or without 0.3% added cholesterol for 3 wk. Among rats fed cholesterol, liver total lipid and cholesterol concentrations were significantly lower in groups fed pectin, psyllium and oat bran compared with cellulose-fed controls. Cholesterol feeding resulted in significantly greater liver cholesterol in rats fed cellulose, psyllium and oat bran but not in those fed pectin. Among rats fed cholesterol, total serum cholesterol levels were significantly lower in those fed pectin than in those fed psyllium, oat bran or cellulose. When cholesterol was fed, the oat bran-fed group had significantly higher butyrate and the pectin-fed group had significantly higher propionate concentrations in the hepatic portal vein than did cellulose-fed controls. The groups fed psyllium, oat bran and pectin all had significantly higher fecal neutral sterols than did the cellulose-fed group when cholesterol was fed. Without dietary cholesterol only pectin-fed rats had significantly higher fecal excretion of neutral sterols than those fed cellulose. Dietary fiber did not influence fecal acidic sterol excretion. However, the addition of cholesterol to these fiber diets was accompanied by a significantly higher bile acid excretion than that of animals fed cellulose without cholesterol. The results of this study indicate that soluble dietary fibers may exert their hypocholesterolemic effect by increasing excretion of fecal neutral sterols.

Comparative efficacy of shilajeet and gum guggal (commiphora mukul) in preventing diet induced hypercholesterolemia in wistar rats

Shilajeet, a polycrest ayurvedic drug hitherto unknown for its hypolipidemic effect has been shown to lower serum cholesterol, liver cholesterol, serum triglycerides and serum phosphlipids of wistar rats fed on a cholesterol (1%) supplemented diet, by 39, 55, 47 and 25 per cent respectively, when 0.2 per cent of it was incorporated in the diet. In comparison, gum guggal (2.0 per cent in the diet) lowered the serum cholesterol, liver cholesterol, serum triglycerides and serum phospholipids by 36, 60, 49 and 8 per cent respectively. The increase in HDL-cholesterol by shilajeet was much higher (53%) compared to that by gum guggal (29%).

Effect of n−3 fatty acids on the key enzymes involved in cholesterol and triglyceride turnover in rat liver

The effect of long-chain n-3 fatty acids on hepatic key enzymes of cholesterol metabolism and triglyceride biosynthesis was investigated in two rat models. In the first model, rats were intravenously infused for two weeks with a fat emulsion containing 20% of triglycerides in which either n-6 or n-3 fatty acids predominated. The treatment with n-3 fatty acids led to a reduction primarily of serum cholesterol (45%), but also of serum triglycerides (18%). HMG-CoA reductase activity and cholesterol 7 alpha-hydroxylase activity were reduced by 45% and 36%, respectively. There were no significant effects on diacylglycerol acyltransferase (DGAT) or phosphatidate phosphohydrolase (PAP) activities. In the second model, rats were fed a diet enriched with sucrose, coconut oil and either sunflower oil (n-6 fatty acids) or fish oil (long-chain n-3 fatty acid ethyl esters). The treatment with n-3 fatty acids decreased serum triglycerides (41%) and, to a lesser extent, serum cholesterol (17%). Neither glycerol 3-phosphate acyltransferase (GPAT) or DGAT were affected by n-3 fatty acids. In contrast, PAP activity was reduced by 26%. HMG-CoA reductase was not significantly affected, whereas cholesterol 7 alpha-hydroxylase activity was reduced by 36%. The results indicate that part of the TG-lowering effect of long-chain n-3 fatty acids may be mediated by inhibition of the soluble phosphatidate phosphohydrolase. The effect on serum cholesterol may be partly due to inhibition of HMG-CoA reductase.

Effect of Dietary Safflower Phospholipid on Plasma and Liver Lipids in Rats Fed a Hypercholesterolemic Diet.

The effect of safflower phospholipid (SP) on plasma and liver lipids in rats fed a hypercholesterolemic diet was examined. Triglyceride mixture (SPO) of safflower oil and palm oil (8:2) containing almost comparable amounts of linoleic acid to safflower phospholipid was used as a control diet. Similarly, the effect of paste safflower phospholipid (PSP) which contains approximately 45% of neutral lipid was also compared to safflower oil (SO). Concentrations of total cholesterol in plasma and liver of rats fed the SP diet were markedly decreased in comparison with those of the other diets, but a slight reduction of total cholesterol in plasma and liver was observed in rats fed PSP diet. SP and PSP induced a reduction in the plasma level of low density lipoprotein (LDL) cholesterol as well as an increase in the level of high density lipoprotein (HDL) cholesterol. The activity of plasma lecithin-cholesterol acyltransferase (LCAT) was greatly increased in rats fed SP diet. These results suggest that the safflower phospholipids suppress the elevation of plasma and liver cholesterol and that this effect may depend on the phospholipid content in dietary lipid.

Regulation of cholesterol 7 alpha-hydroxylase in the liver. Cloning, sequencing, and regulation of cholesterol 7 alpha-hydroxylase mRNA.

Monospecific antibody against purified rat liver cholesterol 7 alpha-hydroxylase cytochrome P-450 was used to screen a lambda gt11 cDNA library constructed from immuno-enriched polysomal RNA of cholestyramine-treated female rat liver. Two types of cDNA clones differing in the length of the 3'-untranslated region were identified, and DNA sequences were determined. The full length clone contains 3561 base pairs plus a long poly(A) tail. The amino acid sequence deduced from the open reading frame revealed a unique P-450 protein containing 503 amino acid residues which belonged to a new gene family designated family VII or CYP7. Southern blot hybridization experiments indicated that the minimal size of P-450 VII gene was 11 kilobase pairs (kb), and there was probably only one gene in this new family. Northern blot hybridization using specific cDNA probes revealed at least two major mRNA species of about 4.0 kb and 2.1 kb, respectively. These two mRNA species may be derived from the use of different polyadenylation signals and reverse-transcribed to two types of cDNA clones. Cholesterol 7 alpha-hydroxylase mRNAs were induced 2- to 3-fold in rat liver by cholestyramine treatment. The mRNA level was rapidly reduced upon the removal of the inducer. Similarly, cholesterol feeding induced enzyme activity, protein, and mRNA levels in the rat by 2-fold, suggesting that cholesterol is an important regulator of cholesterol 7 alpha-hydroxylase in the liver. On the other hand, dexamethasone and pregnenolone-16 alpha-carbonitrile drastically reduced the activity, protein, and mRNA levels. These experiments suggest that the induction of cholesterol 7 alpha-hydroxylase activity by cholestyramine or cholesterol and inhibition of cholesterol 7 alpha-hydroxylase activity by bile acid feedback are results of the rapid turnover of cholesterol 7 alpha-hydroxylase enzyme and mRNA levels.

Rat liver cholesterol 7 alpha-hydroxylase. Pretranslational regulation for circadian rhythm.

A complete cDNA encoding cholesterol 7 alpha-monooxygenase (EC 1.14.13.17) which had been isolated from rat liver cDNA libraries by using specific antibodies to the enzyme (Noshiro, M., Nishimoto, M., and Okuda, K. (1989) FEBS Lett. 257, 97-100) was totally sequenced. The cDNA contained a 1,509-base pair open reading frame encoding 503 amino acid residues (Mr = 56,880) and an unusually long 3'-untranslated region rich in AT sequence in the total length of 3,545 base pairs. The predicted amino acid sequence displays less than 30% similarity to other sequenced cytochrome P-450s indicating that the 7 alpha-hydroxylase constitutes a novel family of cytochrome P-450. The AT-rich region often contained ATTTA motifs, 5'-AAT-3' or 5'-TAA-3' trinucleotides which were reported to be involved in rapidly degrading mRNA. Employing the specific antibodies and the cDNA as probes, a diurnal variation of the levels of the three factors, i.e. enzyme protein, mRNA, and enzyme activity, was studied on rat livers prepared at various times of the day. In normal animals, all three factors exhibited maximum level at 10:00 p.m. and minimum at 10:00 a.m. No significant sexual difference was observed. Cholestyramine feeding increased all three factors at 10:00 a.m. close to the maximum levels of the normal rats, but did not show a significant increase at 10:00 p.m. On the contrary, starvation markedly decreased all three factors either at 10:00 a.m. or at 10:00 p.m., while maintaining still the diurnal variation. A good correlation of the levels of mRNA to the enzyme activities and the protein levels demonstrates that pretranslational regulation is most likely a mechanism for the circadian rhythm of 7 alpha-hydroxylase. The marked diurnal fluctuation of the amount of protein and the level of mRNA also indicates their rapid turnover. The short half-life of mRNA could be correlated with the structure of the 3'-untranslated region of the mRNA characteristic of rapidly degrading mRNA, i.e. abundance of motif, AUUUA, and existence of 5'-AAU-3' or 5'-UAA-3' trinucleotides in single-stranded regions of the secondary structure.

Ultrastructural detection of cholesterol in the liver of alcoholic rats

Ultrastructural detection of cholesterol in the liver of alcoholic rats

Tissue-selective acute effects of inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase on cholesterol biosynthesis in lens.

Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the key enzyme that regulates cholesterol synthesis, lower serum cholesterol by increasing the activity of low density lipoprotein (LDL) receptors in the liver. In rat liver slices, the dose-response curves for inhibition of [14C]acetate incorporation into cholesterol were similar for the active acid forms of lovastatin, simvastatin, and pravastatin. The calculated IC50 values were approximately 20-50 nM for all three drugs. Interest in possible extrahepatic effects of reductase inhibitors is based on recent findings that some inhibitors of HMG-CoA reductase, lovastatin and simvastatin, can cause cataracts in dogs at high doses. To evaluate the effects of these drugs on cholesterol synthesis in the lens, we developed a facile, reproducible ex vivo assay using lenses from weanling rats explanted to tissue culture medium. [14C]Acetate incorporation into cholesterol was proportional to time and to the number of lenses in the incubation and was completely eliminated by high concentrations of inhibitors of HMG-CoA reductase. At the same time, incorporation into free fatty acids was not inhibited. In marked contrast to the liver, the dose-response curve for pravastatin in lens was shifted two orders of magnitude to the right of the curves for lovastatin acid and simvastatin acid. The calculated IC50 values were 4.5 +/- 0.7 nM, 5.2 +/- 1.5 nM, and 469 +/- 42 nM for lovastatin acid, simvastatin acid, and pravastatin, respectively. Thus, while equally active in the liver, pravastatin was 100-fold less inhibitory in the lens compared to lovastatin and simvastatin. Similar selectivity was observed with rabbit lens. Following oral dosing, ex vivo inhibition of [14C]acetate incorporation into cholesterol in rat liver was similar for lovastatin and pravastatin, but cholesterol synthesis in lens was inhibited by lovastatin by as much as 70%. This inhibition was dose-dependent and no inhibition in lens was observed with pravastatin even at very high doses. This tissue-selective inhibition of sterol synthesis by pravastatin was likely due to the inability of pravastatin to enter the intact lens since pravastatin and lovastatin acid were equally effective inhibitors of HMG-CoA reductase enzyme activity in whole lens homogenates. We conclude that pravastatin is tissue-selective with respect to lens and liver in its ability to inhibit cholesterol synthesis.

Activation of rat liver cholesterol ester hydrolase by cAMP‐dependent protein kinase and protein kinase C

Short term regulation of hepatic cholesterol ester hydrolase by reversible phosphorylation is described. Two different kinase systems seem to be involved in this regulation. The addition of ATP, cyclic AMP and Mg2+ to rat liver 104,000 X g supernatant (S104) produced a 100-140% increase in cholesterol ester hydrolase activity. This stimulation was abolished when protein kinase inhibitor was added prior to the addition of ATP, cyclic AMP and Mg2+. Cholesterol ester hydrolase activity was also stimulated when calcium ions, phosphatidylserine, and diolein were added to S104 along with ATP and Mg2+. Diolein in this reaction could be substituted by phorbol 12-myristate 13-acetate. Preincubation of S104 with alkaline phosphatase resulted in a deactivation of cholesterol ester hydrolase. The addition of increasing concentrations of Mg2+ to S104 produced increasing inhibition of cholesterol ester hydrolase activity, and this effect was blocked by NaF. It is suggested that rat liver cholesterol ester hydrolase is activated by cyclic AMP dependent protein kinase and protein kinase C. Deactivation is accomplished by dephosphorylation catalyzed by a phosphoprotein phosphatase, dependent on Mg2+.

Interaction of dietary protein, cholesterol and age on lipid metabolism of the rat.

1. Male rats at 1 (young) and 9 months (adult) of age were fed on purified diets, supplemented with or without cholesterol, containing 200 g protein/kg (casein (CAS), whey protein (WHY) or soya-bean protein (SOY] for 4 weeks. 2. SOY exerted a hypocholesterolaemic effect in young rats regardless of dietary cholesterol, whereas in adult rats it was observed only when a cholesterol-enriched diet was given. WHY was also hypocholesterolaemic in rats of both ages given cholesterol. SOY tended to reduce the liver cholesterol both in young and adult rats. 3. The liver hydroxymethylglutaryl-CoA reductase (NADPH) (EC 1.1.1.34) activity tended to be lower in the vegetable-protein groups than in the animal-protein groups in young rats, but the age-related reduction was observed only in the latter groups. 4. There was no significant age-related difference in the activity of liver cholesterol 7 alpha-monooxygenase (EC 1.14.13.17) in response to diets. However, when cholesterol was given, activity tended to decrease with age. Rats given SOY excreted more faecal steroids than those given casein, particularly adult rats. 5. The fatty acid profile of phosphatidylcholine and the delta 6-desaturase activity of liver microsomes indicated the reduced desaturation of linoleate in the SOY and WHY groups compared with the CAS groups. 6. The results thus showed a complex interaction of protein type, cholesterol and age on cholesterol homeostasis.

Effects of dietary carbohydrates on cholesterol metabolism in rats of different ages.

Male Sprague-Dawley rats aged 1 month (young) and 9 months (adult) were fed diets containing sucrose, glucose or corn starch as a carbohydrate source for 4 weeks. Dietary sucrose increased (a) the liver size in rats of both ages, (b) the serum cholesterol level in adult rats, (c) the serum triglyceride level, especially in young rats, and (d) the liver cholesterol and triglyceride levels in adult rats. Consequently, there were age-related increases in serum and liver cholesterol in rats fed sucrose. No significant difference was found in the activity of liver 3-hydroxy-3-methylgIutaryI coenzyme A reductase due to the diets in age-matched rats, whereas an age-related decrease was observed in rats fed simple sugars. Rats fed sucrose, especially adult rats, excreted more fecal steroids than ones fed glucose or corn starch. Sucrose tended to enhance the metabolism of linoleate to arachidonate, as judged from the fatty acid composition of liver microsomal phosphatidylcholine. Thus, sucrose exerts a peculiar effect on cholesterol metabolism in relation to age.