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Biomedical subjects

M Sugano

Publications and source records attributed to M Sugano.

At least 289 records · Page 16Linked to original sources

Further studies on the hypocholesterolaemic effect of soya-bean protein in rats.

1. The hypocholesterolaemic effect of soya-bean protein compared with that of casein, when fed at 200 g/kg diet for 3 weeks, was studied in rats. 2. Using a cholesterol-free low-fat (10 g maize oil/kg) diet, the hypocholesterolaemic effect was demonstrated not only with soya-bean protein but also with an amino acid mixture simulating this protein. The addition of lysine to these diets did not modify their intrinsic effects on serum cholesterol. 3. By feeding the vegetable protein or its amino acid mixture, both high-density-lipoprotein-and very-low-density-lipoprotein plus low-density-lipoprotein-cholesterol decreased to a similar extent, and the concentration of serum apolipoprotein A--I decreased and that of apolipoprotein B increased. 4. Although rats given soya-bean protein excreted more neutral and acidic steroids, the difference disappeared when the amino acid mixture was fed, indicating that the hypocholesterolaemic effect of the vegetable protein is not ascribed only to the increased elimination of steroids. 5. It is likely that the difference in the amino acid composition between animal and vegetable proteins is in fact responsible for the different response of serum cholesterol.

Amino Acids↗

Antihypercholesterolemic activity of beta-sitostanol in rabbits.

The antihypercholesterolemic activity of beta-sitosterol and beta-sitostanol was compared in male rabbits given a cholesterol-supplemented diet. beta-Sitosterol and beta-sitostanol were fed to these rabbits at the 0.5% level with cholesterol (0.5% and 0.2% in experiments I and II, respectively). The serum cholesterol level tended to be lower in rabbits fed beta-sitostanol than in the animals fed beta-sitosterol even in experiment I. The beta-sitostanol exhibited a significantly greater hypocholesterolemic activity in experiment II, LDL-cholesterol being decreased markedly. The liver cholesterol decreased in both groups of rabbits to a similar extent. beta-Sitostanol prevented more effectively the formation of dietary cholesterol-induced atheroma in the abdominal aorta than beta-sitosterol. It is most likely, together with the data reported previously on rats, that the hypocholesterolemic activity of beta-sitostanol results from the significantly greater inhibitory effect on the intestinal absorption of cholesterol than that of beta-sitosterol.

Animals↗

Effects of dietary soybean globulins on plasma and liver lipids and on fecal excretion of neutral sterols in rats.

Effects of low-fat (1% corn oil) diets containing an isonitrogenous level (3.2%) of either casein, soybean protein isolate or three soybean globulin fractions (total, 11S and 7S globulins) on plasma and liver lipids and on the excretion of fecal neutral sterols were examined in rats. When diets free of cholesterol were fed, the concentration of plasma cholesterol was significantly lower in all groups of rats given different soybean proteins than in the animals given casein. 11S globulin tended to produce a lower level of plasma cholesterol as compared with the 7S counterpart. Although the net decrease due to feeding plant proteins in high density lipoprotein cholesterol was to some extent greater than that of very low and low density lipoprotein cholesterol, the percentage of the former to total cholesterol remained in the normal range. The concentration of liver cholesterol appeared to be lower in rats given soybean proteins. Rats fed soybean globulins, as compared with the animals fed casein, tended to excrete larger amounts of neutral sterol into the feces. These soybean-effects disappeared when cholesterol and cholic acid were added to diets. The results indicated that the antihypercholesterolemic effect of soybean protein was attributable to protein per se, and not to the carbohydrate components which were associated with the protein preparation.

Amino Acids↗

Serum and liver cholesterol levels of rats and mice fed soy-bean protein or casein.

Rats and mice were fed soy-bean protein or casein diets for 10 and 50 weeks, respectively, during which terms their serum cholesterol levels were analyzed periodically. Rats fed high-cholesterol diets containing soy protein or the amino acid mixture simulating soy protein produced lower levels of serum cholesterol throughout the experiments, as compared with those on the corresponding casein-type diets. Feeding soy protein resulted in a significant decrease in serum apoA-I and apoB, but the relative concentration of high-density lipoprotein-cholesterol was kept at the higher level. The concentration of liver cholesterol was also lower in rats fed the plant protein. In mice fed a cholesterol-free diet, the cholesterol-lowering effect of soy protein was noticeable at an early stage of the feeding periods, by 20 weeks. The extent of lipid peroxidation in rats and mice determined as TBA-reactive substances in serum was found to be the same when protein diets were given, while it was significantly higher when an amino acid mixture of the soy protein type was fed to rats. The results confirm that soy protein exhibits its hypocholesterolemic effect even when a diet rich in cholesterol is fed. The cholesterol-lowering effect of soy proteins appears to be a phenomenon common to rodents.

Animals↗

Effects of soya-bean protein and casein on serum cholesterol levels in rats.

1. The effect of the soya-bean protein isolate and casein, both given 200 g/kg diet for 3-4 weeks, on serum cholesterol was compared in male rats. 2. Soya-bean protein exerted a hypocholesteramic effect only in a cholesterol-free low-fat (10 g maize oil/kg) diet, when the lowering action appeared independent of the strain of the rat or the feeding pattern. The results obtained with diets containing cholesterol or higher levels of fats or both showed no definite pattern of response. 3. Although the decrease in serum cholesterol appeared greater in alpha-lipoproteins than in beta-lipoproteins, the proportion of the former to total cholesterol remained almost unchanged. The concentration of serum apo A-I was significantly lower in rats given the vegetable protein. 4. Rats given soya-bean protein excreted significantly more neutral sterols. 5. The serum amino acid pattern did not reflect the difference in dietary protein. Addition of cholesterol to the diets modified the serum aminogarm, the decrease in threonine being most marked in both protein groups. 6. This study shows that the hypocholesteraemic action of soya-bean protein is easily modified by the type of diet.

Animals↗

A novel use of chitosan as a hypocholesterolemic agent in rats.

A series of experiments with male rats clearly demonstrated the hypocholesterolemic activity of dietary chitosan. On feeding a high cholesterol diet for 20 days, addition of 2 to 5% chitosan resulted in a significant reduction, by 25 to 30%, of plasma cholesterol without influencing food intake and growth. The concentration of liver cholesterol and triglyceride also decreased significantly. Plasma, but not liver cholesterol-lowering effect, was roughly comparable with that of cholestyramine. Chitosan at the 10% level further reduced plasma cholesterol, but depressed growth. Also, finer chitosan particles tended to restrain growth even at the 2% level. In rats fed a cholesterol-free diet containing 0.5% chitosan for 81 days, the concentration of serum cholesterol was the same with that of the corresponding control, but relatively more cholesterol existed as high-density lipiproteins and less as very low-density lipoproteins. Dietary chitosan increased fecal excretion of cholesterol, both exogenous and endogenous, while that of bile acids remained unchanged. There was no constipation or diarrhea. A proper supplementation of chitosan to the diet seemed to be effective in lowering plasma cholesterol.

Animals↗

Dietary regulation of hepatic 3-hydroxy-3-methylglutaryl-CoA reductase and cholesterol synthetic activities in fasted-refed rats.

Effects of dietary cholesterol, beta-sitosterol and cholestyramine on hepatic HMG-CoA reductase activity and sterogenesis were examined in male rats refed different types and amounts of fats for 3 days after fasting 2 days. Safflower oil (10%) decreased reductase and sterogenic activities more than saturated fat or low fat. Reductase activity and sterogenesis decreased as dietary cholesterol increased; this was not influenced by the type of dietary fat. Although cholesterol as low as 0.01% depressed these activities, more cholesterol was required to deposit cholesterol in the livcreased cholesterol excretion as neutral steroids but failed to enhance reductase and sterogenic activities. In contrast, cholestyramine increased these activities to approximately the same level irrespective of the type and amount of dietary fat. Hepatic cholesterol decreased only in rats refed saturated fat; neutral or acidic steroid excretion was greatest in this group. Hepatic cholesterol and enterohepatically circulating cholesterol may not be critical factors in regulating HMG-CoA reductase in fasted-refed rats. Rather, the quantity of bile acids fluxed to the liver appears to influence the reductase activity in this situation. However, analyses of fecal acidic steroids provided no evidence for a relationship between HMG-CoA reductase activity, bile acid metabolism and dietary fat.

Animals↗

Dietary modification of the distribution of 3-hydroxy-3-methylglutaryl coenzyme A reductase and sterol synthesizing activities in the rat small intestine.

The distribution of microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase in the rat small intestine was modified by the type of the diets. The reductase activity in rats fed a commercial non-purified diet (rat chow) was markedly higher in the ileum than in the jejunum, while this pattern was reversed in animals fed a purified diet. Feeding a fat-containing purified diet, in comparison with a fat-free diet, resulted in a significant increase in the activity of the villous reductase. In rats fed a purified diet, the synthesis of digitonin precipitable sterols from [1-14C]acetate in vivo was considerably higher in rats fed a purified diet than in the animals fed a non-purified diet. Although responses to various measurements were not always consistent, the observation that the type of the diet modifies specifically the intra- and inter-tissue distribution of cholesterol synthesizing activity in the intestine strongly stresses the necessity of appropriate sectioning of the tissues, particularly in comparative studies. Also, comparisons of the sterogenesis of the small bowel and liver denote the possibility that intestinal contribution to endogenous cholesterol synthesis is considerably greater than previously estimated, even in the absence of dietary cholesterol.

Animals↗

Some observations on the cholesterol esterifying and cholesterol ester hydrolyzing activities in dog plasma.

Cholesterol esterification and cholesterol ester hydrolysis in dog plasma were investigated. Esterification proceeded linearly for 60 min, and the amounts of cholesterol esterified were in the range of 0.13-0.18 mumol/ml/h. No change of acyl composition had occurred in newly formed cholesterol esters during incubation. With the addition of Na taurocholate (10 mM), complete inhibition of the esterifying activity and maximal activation of the hydrolase activity were observed. Approximately 50% of cholesterol esters present in plasma was hydrolyzed in 10 min of incubation, and the reaction was completed within 60 min. The maximal rate of hydrolysis was estimated to be 4.0-5.4 mumol/ml/h, and polyunsaturated esters were hydrolyzed more rapidly than saturated ones. The esterifying activity was detected in high density (HDL) and very high density lipoproteins (VHDL), while the hydrolytic activity was found only in VHDL. Each lipoprotein fraction served as a good substrate for hydrolysis, while HDL was the sole substrate for esterification. The optimal pH of the hydrolytic activity in VHDL lay in a broad range between 6.8 and 7.2 and the apparent Km was determined as 12.5 x 10(-3) mM for cholesteryl oleate.

Animals↗

Lipid composition and cholesterol esterification in serum lipoprotein fraction of the horse, Equus caballus.

1. Changes in lipid components of lipoproteins during incubation of horse serum at 37 degrees C were investigated. In non-incubated serum, cholesterol and lecithin existed predominantly in alpha-lipoprotein or in high-density lipoprotein (HDL). Lysolecithin was mainly associated with the fraction with density above 1.21. 2. When serum was separated into alpha- and beta-lipoproteins by the heparin precipitation method after 1 hr incubation, the decrease in alpha-lipoprotein free cholesterol and lecithin was about four times that in beta-lipoprotein counterparts. 3. When serum lipoproteins were separated by ultracentrifugation, the decrease in each lipoprotein free cholesterol was closely paralleled with that in lecithin. 4. HDL appeared to be a preferential substrate for the lecithin: cholesterol acyltransferase reaction. 5. Disc electrophoretic patterns indicated significant differences in the composition of horse serum lipoproteins from those of human and rat.

Animals↗

Serum and liver lipid composition and lecithin: cholesterol acyltransferase in horses, Equus caballus.

1. The lipid composition of serum and liver and some properties of serum lecithin: cholesterol acyltransferase of the horse were investigated. 2. Phospholipids and cholesterol were the major components of serum lipids and the concentration of triglyceride was considerably low. The concentration of liver lipids was comparable with that of other mammals. 3. Fatty acid composition of serum cholesterol ester resembled that of the 2-position of lecithin, except palmitic acid. 4. The activity of serum cholesterol esterifying enzyme was found to be 0.03-0.09 mumol/hr per ml. There was an equimolar decrease in free cholesterol and lecithin during incubation, and changes in unsaturated fatty acids in these two components were in good agreement. 5. Cholesterol esterification was reversibly inhibited by 5,5'-dithiobis-(2-nitrobenzoic acid). The acyl-transferase had a specificity for linoleic acid.

Animals↗

Dietary fat-dependent changes in hepatic cholesterogenesis and the activity of 3-hydroxy-3-methylglutaryl-CoA reductase in fasted-refed rats.

Effects of various dietary fats on the activity of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase and sterol and fatty acid synthesis from [1-14C]acetate and [2-14C]mevalonate were examined in the liver from fasted-refed rats. Rats fasted for 2 days were refed a fat-free diet or diets containing various fats (tricaprylin, trilaurin, trimyristin, tristearin, camellia oil, or safflower oil) at the 10% level for 1, 3, or 7 days. The activity of HMG-CoA reductase was restored to about one-half of the pre-fasting levels in all groups after refeeding for 1 day and increased to above the pre-fasting levels after 3 days, with the exception of safflower oil, the rise was especially noticeable when fat-free, tricaprylin, and tristearin diets were fed. After 7 days, the activity of HMG-CoA reductase, except for rats refed tristearin, was decreased to levels that were far below those observed after 1 day-refeeding. This was particularly marked with tricaprylin, trilaurin, and camellia oil. The response of sterogenesis resembled that of the reductase. Dietary fat-dependent modification of fatty acid synthesis from [1-14C]acetate was first demonstrated after 7 days. Hepatic esterified cholesterol tended to accumulate and the deposition was marked after 3 days of refeeding. However, fat-dependent alterations of this parameter were remarkable on day 7. The concentration of plasma cholesterol also showed dietary fat-dependent changes after refeeding. Dietary fats appear to play an important role not only in the regulation of hepatic HMG-CoA reductase and sterol synthesis, but also in the overall processes of cholesterol dynamics.

Animals↗

Effects of exercise on plasma and liver lipids of rats. IV. Effects of exercise on hepatic cholesterogenesis and fecal steroid excretion in rats.

The effects of treadmill exercise on hepatic cholesterogenesis and fecal steroid excretion were studied using male Wistar rats fed a commercial pellet ration. Exercise, in comparison with ad libitum or pair-feeding sedentary groups, caused the following significant changes: (i) a reduction in the concentration of plasma triglyceride, phospholipid and cholesterol; (ii) a reduction in liver weight; (iii) increases in hepatic 3-hydroxy-3-methylglutaryl-CoA reductase activity and incorporation of mevalonate into digitonin precipitable sterol; (iv) increases in excretion of neutral and acidic steroids into the feces; (v) the increase in lipoprotein lipase activity in the cardiac muscle, and (vi) the decrease in the concentration of carcass triglyceride but not of cholesterol. These data suggest that the mechanism responsible for the plasma cholesterol-lowering effect of exercise is attributable to an increase in exretion of fecal neutral and acidic steroids accompanied by an acceleration of cholesterol turnover in the body.

Animals↗

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

Rats were fed plant sterols containing campesterol and beta-sitosterol in the differerent 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 sterols.

Animals↗

Comparison of absorption and metabolism of beta-sitosterol and beta-sitostanol in rats.

The fates of [4-14C]beta-sitosterol ([14C]S) and [4-14C]beta-sitostanol ([14C]HS) were compared after after oral or intravenous administration to rats. Excretion into feces of oral [14C]HS was significantly higher than that of [14C]S. More than 97% of [14C]HS and 88% of [14CS]S were recovered in the feces within 7 days. Thus, deposition of [14C]HS was negligible in the tissues that were examined. Turnover in serum of [14C]HS which was injected intravenously appeared to be more rapid than that of [14C]S; [14C]HS was excreted as neutral steroids at a rate more than twice that of [14C]S. The rate of excretion of [3H]cholesterol was slightly greater when HS was administered simultaneously. The liver contained significantly less radioactivity after [14C]HS than after [14C]S administration. More [14C]HS than [14C]S was present in esterified form in serum and liver. The ratio of sterol in very low density lipoprotein to that in high density lipoprotein was less for HS or S than for endogenous cholesterol; this was particularly marked with HS. These results suggest that HS would be a more effective hypocholesterolemic agent than S.

Administration, Oral↗