Search PubMed⌕ Search

Biomedical subjects

M Sugano

Publications and source records attributed to M Sugano.

At least 271 records · Page 15Linked to original sources

Cholesterol dynamics in rats fed cis- and trans-octadecenoate in the form of triglyceride.

The cholesterol dynamics were compared in rats fed diets containing either camellia oil or partially hydrogenated corn oil as a source of cis- and trans-octadecenoate, respectively. The diets contained approximately the same amount of octadecenoic acid, and an equivalent amount of linoleic acid. In rats fed the trans-fat for about 30 days, liver cholesterol levels were clearly low relative to levels in rats fed the cis-fat, while the concentration of serum cholesterol and the distribution of cholesterol in serum lipoproteins were comparable. The activity of hepatic microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase and the incorporation of [I-14C]acetate into digitonin-precipitable sterols in the liver homogenate tended to increase in rats fed the trans-fat diet. Cholesterol 7 alpha-hydroxylase activity increased significantly. Cholesterol absorption measured by the dual isotope serum ratio method was markedly lower, and much more radioactivity both from orally and intravenously administered cholesterol was excreted quickly into feces in the trans-fat group, with relatively more excretion in the neutral than in the acidic steroids. Apparent absorption of dietary fat was slightly lower in the trans-fat group. Cholesterol turnover as analyzed according to the two-pool model was much faster in rats fed trans-fat and the pool A size was reduced mainly as a consequence of stimulation of the removal rate from this pool. The intestinal epithelial cells contained relatively more trans-octadecenoate compared to the serum and liver and trans-fat modified the lipid composition specifically. These observations suggest that the changes in cholesterol metabolism due to the ingestion of trans-fat, compared to cis-fat, are as a result of metabolic events in the intestine.

Absorption↗

Effect of clofibrate on the metabolism of oleate in the perfused rat liver.

The effect of clofibrate on the metabolism of [1-14C]- and [U-14C]oleate was examined in the perfused rat liver. Clofibrate feeding severely reduced hepatic triglyceride secretion and enhanced ketone body production. The increase in the rate of incorporation of labeled tracers into perfusate oxidation products and ketone bodies due to the clofibrate treatment was demonstrated only with [U-14C]oleate. Clofibrate strongly reduced the rate of incorporation of oleate into perfusate triglyceride, whereas that into the phospholipid fraction of the post-perfused liver doubled. In consequence, the sum of the radioactivities in esterified lipids in the perfusate and the post-perfused liver was not altered by clofibrate. A clofibrate-dependent increase in phospholipid synthesis may restrict the amount of exogenous fatty acid which is available for the formation of triglyceride-rich lipoproteins.

Animals↗

Some aspects of mechanism of inhibition of cholesterol absorption by beta-sitosterol.

Mixed bile salt micelle solubilized either cholesterol or beta-sitosterol to a comparable extent. When added simultaneously, beta-sitosterol restricted the micellar solubility of cholesterol. beta-Sitosterol also reduced the cholesterol content in the aqueous (micellar) phase of the intestinal contents of rats, the extent of reduction being comparable with that observed in vitro. The intestinal uptake of cholesterol in vivo was equivalent to the micellar incorporation of cholesterol both in vitro and in vivo. beta-Sitosterol had no inhibitory effect on cholesterol absorption from the micellar solution in jejunal loops in situ, whereas the rate of beta-sitosterol uptake was only about one-fifth that of cholesterol. The intestinal uptake of beta-sitosterol intubated into the stomach of rats was about one-fifth that of cholesterol. The intestinal brush-border membrane discriminated these sterols. These results suggest that the restriction of the micellar solubility of cholesterol, rather than the inhibition of uptake from brush-border membrane, is the major determinant for the interference of beta-sitosterol with cholesterol absorption.

Animals↗

Biliary and fecal steroid excretion in rats fed partially hydrogenated soybean oil.

Male Wistar rats were fed cholesterol-free or cholesterol-enriched diets containing partially hydrogenated soybean oil with different levels of trans-fatty acids or unhydrogenated soybean oil at the 10% level. The linoleic acid content of hydrogenated fat diets was adjusted to 3.6% of the total energy. Hydrogenated fat diets contained 29% and 41% trans-acids, mainly as t-18:1. Trans-fats exerted no untoward effects on growth parameters, but increased liver weight. Dietary hydrogenated fats influenced neither the concentration nor composition of biliary steroids, irrespective of the presence or absence of cholesterol in the diet. In rats fed a cholesterol-free diet, daily fecal output of neutral and acidic steroids was enhanced by hydrogenated fats and the magnitude of augmentation was proportional to the dietary level of trans-fatty acids. The increased fecal steroid excretion corresponded to an increase in total excreta. Hydrogenated fats also tended to enhance bile acid excretion when feeding a cholesterol-enriched diet. The results suggest that dietary trans-fatty acids, in relation to cis-polyunsaturated fatty acids, provoke demonstrable change in steroid homeodynamics.

Animals↗

Effects of dietary trans-fat on biliary and fecal steroid excretion and serum lipoproteins in rats.

Rats were fed cholesterol-free or cholesterol-enriched diets containing olive oil or partially hydrogenated corn oil at the 10% level for ca. 30 days (c-18:1, 77.0% in the former diet and c-18:1,24.7% and t-18:1,42.5% in the latter). The linoleic acid content of these fat diets was made equivalent (1.7 energy %). After feeding cholesterol-free diets, trans fat compared to cis fat showed (a) no untoward effects on growth parameters, (b) a reduction of serum cholesterol levels without influencing concentrations of serum apolipoproteins A-1, B and E, (c) no effects on the bile flow and the concentration of biliary cholesterol and bile acids, (d) an increasing trend of fecal excretion of neutral and acidic steroids, both in terms of mg/day and mg/g feces, and (e) rather equivocal change in the composition of fecal, but not biliary steroids. Similar response patterns were also observed when cholesterol-enriched diets were fed except for a decrease in serum apo B and an ineffectiveness to increase fecal acidic steroids. Together with the results obtained from experiments simultaneously performed with safflower oil and completely hydrogenated corn oil, it seems that the steroid metabolism can be specifically modified by the geometry of dietary fats.

Animals↗

The contrasting effect of dietary phosphatidylethanolamine and phosphatidylcholine on serum lipoproteins and liver lipids in rats.

The effect of dietary phosphatidylethanolamine (PE) and phosphatidylcholine (PC) added to cholesterol-free semipurified diet on serum lipoprotein and hepatic and fecal lipids was compared to the effect on rats fed soybean oil (controls). The dietary PE, but not PC, caused a decrease in serum cholesterol, phospholipid, apolipoprotein A-I (apoA-I) and apoE and an increase in high molecular weight apoB. The simultaneous addition of PC and ethanolamine also decreased serum apoA-I and cholesterol. The distribution patterns of phospholipid subclasses in the liver and fatty acid composition of hepatic and plasma phospholipids were also altered by dietary PE. Both PE and PC increased to a similar extent the excretion of fecal neutral steroids and hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity compared to the controls. The present study, therefore, demonstrated for the first time that the PE in the soybean phospholipid preparation is responsible for the alterations of profiles of serum lipids and apoproteins in rats.

Animals↗

Effects of dietary proteins on the intestinal synthesis and transport of cholesterol and apolipoprotein A-I in rats.

Feeding a low-fat diet free of cholesterol to rats resulted in a low level of serum cholesterol and apolipoprotein A-1 (apoA-I) when dietary protein was soybean protein as compared to casein. Since the small intestine is an important synthetic site for lipoproteins, the effects of dietary protein sources on the intestinal synthesis in vitro of cholesterol and apoA-I and the concentration of these components in the mesenteric lymph were studied. In rats fed a 1% fat diet, the apoA-I concentration in the lymph and the de novo synthesis of apoA-I in the small intestine segment were both low for animals fed a soybean protein diet as compared to a casein diet. The intestinal hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase activity was high in animals fed soybean protein, whereas the lymph cholesterol level was comparable. Even in rats fed a 5% fat diet, concentrations of serum cholesterol and apoA-I and lymphatic apoA-I were again significantly low for rats fed vegetable protein. These results indicate that the intestine plays an important role in the dietary protein-dependent regulation of serum cholesterol and apoA-I levels.

Animals↗

Hepatic secretion of lipids and apolipoproteins in rats fed soybean phospholipid and soybean oil.

Dietary phospholipid (PL) containing phosphatidylethanolamine alters serum lipoproteins in rats. To clarify the underlying mechanism for the alteration of serum lipids and apolipoproteins, secretions of lipids and apolipoproteins from isolated perfused livers in rats fed soybean PL or soybean oil were compared in this study. Soybean PL significantly decreased the rates of accumulation of apolipoprotein A-I (apoA-I) and cholesterol in the liver perfusate. The secretion of newly synthesized apoA-I labeled with [3H]lysine into the perfusate also significantly decreased in rats fed soybean PL. The secretion patterns of triglyceride and apolipoproteins other than apoA-I were similar for rats fed either diet. Constant infusion of oleic acid into the liver perfusion medium did not alter the response of the secretion of lipids and apolipoproteins to soybean PL feeding. In rats injected with Triton WR-1339, concentrations of serum triglyceride and high-molecular-weight apoB at 20 hours after injection were significantly increased by soybean PL feeding, whereas until 2 hours postinjection the accumulation of serum triglyceride was similar for rats fed either diet. Thus, soybean PL affects not only secretion of hepatic lipoproteins but also metabolism of triglyceride-rich lipoproteins derived from the liver.

Animals↗

Reciprocal responses to clofibrate in ketogenesis and triglyceride and cholesterol secretion in isolated rat liver.

The effect of clofibrate on the production of ketone bodies and the secretion of lipids was examined in the isolated rat liver. Feeding of clofibrate (0.3% in the diet) for a week caused the liver enlargement. The drug increased ketone body production and conversely decreased the secretion of triglyceride and cholesterol in the perfused liver, in particular when oleate was provided to the perfusion medium. Fractionation of the liver perfusate at the density of 1.006 g/ml showed that changes in the rate of lipid secretion were largely due to the modification of the rate of very low density lipoprotein secretion. These observations indicated that the enhancement of fatty acid oxidation by clofibrate resulted in the concomitant decrease in the flux of free fatty acid into triglyceride synthesis and subsequent formation and secretion of triglyceride-rich lipoproteins in the liver. Measurement of activities of enzymes involved in hepatic cholesterogenesis proved that the alteration of the rate of hepatic cholesterogenesis might not be a factor responsible for the hypocholesterolemic action of clofibrate.

Animals↗

Effects of arginine and lysine addition to casein and soya-bean protein on serum lipids, apolipoproteins, insulin and glucagon in rats.

1. The effect of variation in arginine: lysine on the relative cholesterolaemic effects of dietary soya-bean protein and casein was studied. Male rats received semi-purified diets containing soya-bean protein isolate or casein supplemented respectively with varying amounts of lysine or arginine for 40 d and blood samples were taken after a 5 h fast. 2. Neither the addition of arginine to casein nor lysine to soya-bean protein modified the intrinsic effect of these proteins on serum cholesterol. 3. Serum triglyceride levels tended to rise with increasing amounts of lysine supplementation. The opposite trend was obtained with arginine supplementation. 4. Casein caused an increase in the concentration of serum insulin, but not glucagon. The glucagon level was increased proportionately with increasing amounts of arginine, while the addition of lysine showed no effect. The effects of added amino acids on serum insulin were inconclusive. 5. There was a parallel increase in serum apo E and glucagon in response to arginine supplementation, while lysine supplementation increased serum apo E. 6. Thus, arginine: lysine was more effective in regulating serum triglyceride than serum cholesterol. Insulin was associated with different effects of these proteins on serum lipids.

Animals↗

3-hydroxy-3-methylglutaryl coenzyme A reductase activity in the small intestine of rats fed non-purified and semipurified diets.

The effects of diet types on microsomal 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase in the intestinal villus and crypt cells isolated by scraping were studied in rats. The jejunoileal gradient for the reductase specific activity, a phenomenon usually observable in rats fed a commercial non-purified diet, disappeared when sucrose- or glucose-enriched semipurified diets were ingested. Feeding these semipurified diets resulted in a significant increase in reductase activity in jejunal villi and crypts with a concomitant decrease in that of the ileal populations. Neutral detergent fiber prepared from the non-purified diet, but not cellulose powder, when included to semipurified diets at the levels equivalent to those in the non-purified diet, eliminated the ileojejunal gradient, reductase activity was virtually the same in the proximal and distal portions of the intestine or the distribution pattern resembled that shown in rats fed a non-purified diet. Potato and corn starches replaced for sucrose in a low-fiber semipurified diet were also effective for elimination of the gradient, but wheat starch was less effective in the respect. It is clear that intestinal sterogenesis via HMG-CoA reductase is specifically regulated by the complex interplay of dietary components, in particular carbohydrate sources.

Animals↗

Secretion of cholesterol, triglyceride and apolipoprotein A-I by isolated perfused liver from rats fed soybean protein and casein or their amino acid mixtures.

Isolated livers from rats fed soybean protein isolate and casein or amino acid mixtures simulating these proteins were perfused for 4 hours with Krebs-Henseleit buffer containing 0.15% glucose and 25% human red blood cells. Feeding soybean protein as compared with casein resulted in a significant reduction of the secretion of cholesterol, triglyceride and apo A-I. The results agreed well with the responses of serum counterparts reported previously. When amino acid mixture diets were fed, however, no such difference could be demonstrated, though the soy-type amino acid mixture had also been shown to decrease serum cholesterol and apo A-I. The production rate of total ketone bodies was the same, but the ratio of beta-hydroxybutyrate:acetoacetate was significantly higher in rats fed plant protein. The perfusate glucose tended to be higher on soybean protein. These differences were less clear on feeding amino acid mixtures. Neither the rate of bile flow nor the concentration of biliary bile acids and cholesterol were influenced by the type of dietary protein. These observations led us to conclude that soybean protein exerts the cholesterol-lowering action primarily through the regulation of hepatic contribution. The data also suggested that the protein-dependent difference in the concentration of serum cholesterol and apo A-I might not be explained thoroughly by the difference in the amino acid profile alone.

Amino Acids↗

Studies on the mechanism of antihypercholesterolemic action of soy protein and soy protein-type amino acid mixtures in relation to the casein counterparts in rats.

Given evidence of a hypocholesterolemic effect in rats, soy protein compared with casein showed the following effects on cholesterol dynamics: a) lower cholesterol absorption and greater fecal steroid excretion, b) more rapid turnover of serum cholesterol, c) a marked size reduction of the rapidly exchangeable cholesterol pool (pool A) through a significant increase in the removal rate in that compartment without influencing the production rate, and d) greater hepatic sterogenesis both in vitro and in vivo. In contrast, the amino acid mixture equivalent to soy protein compared with casein-type mixture showed: a) no effects on cholesterol absorption and fecal steroid excretion, b) no effects on the turnover of serum cholesterol, c) the reduction of pool A size as a result of decreased production, and d) the reduction of hepatic steroidogenesis in vitro, but not in vivo. These results indicate that decreased intestinal absorption of cholesterol, and increased fecal steroid excretion are primarily responsible for the antihypercholesterolemic effect of soy protein compared with casein. The fecal loss of steroids far outweighs the activation of hepatic steroidogenesis. In the case of the soy protein-type amino acid mixture, the depression of hepatic cholesterol synthesis seems accountable for reducing serum cholesterol levels.

Absorption↗

Effect of dietary phospholipids and their constituent bases on serum lipids and apolipoproteins in rats.

To evaluate alterations of serum lipoproteins, liver lipids and fecal sterol excretion caused by feeding a crude soybean phospholipid preparation, the effect of purified phospholipids and phospholipid bases were studied in rats. Soybean phosphatidylcholine preparations showed no effect on serum lipoproteins and liver lipids. Egg yolk phospholipid, which contained phosphatidylethanolamine and phosphatidylcholine, caused a decrease in serum cholesterol and apoprotein A-I and an increase in serum apoprotein B and liver cholesterol. Ethanolamine, but not choline and inositol, showed an effect on serum lipoproteins similar to egg yolk phospholipid. All phospholipids tested increased fecal excretion of neutral sterols. It is suggested that phosphatidylethanolamine exerts marked influence on serum lipoprotein levels.

Animals↗

Effects of beta-sitosterol on the concentrations of serum and liver cholesterol and serum apolipoproteins in rats fed butter fat.

Male rats were fed on semipurified cholesterol-free diets containing butter fat with or without supplementary beta-sitosterol. The expected rise of serum cholesterol caused by butter fat, as compared with safflower oil, was not able to be demonstrated, and hence the hypocholesterolemic effect of beta-sitosterol as well. However, the plant sterol effectively lowered the liver cholesterol level. Similar responses were also observed in mice. The distribution of cholesterol in serum lipoproteins remained unchanged among different dietary regimens. Butter fat increased the concentration of serum apoA-I in relation to safflower oil. There was possibly a trend toward higher serum apoA-I with supplementation of beta-sitosterol in a butter-fat diet. The effect of the plant sterol on serum apoB was rather variable. The observation strongly suggests that alteration in cholesterol metabolism in these rodents may not satisfactorily be estimated by the serum cholesterol parameter alone when diets free of cholesterol are fed. The concentration of hepatic cholesterol and serum apolipoproteins seems a more apposite measure for this purpose.

Animals↗

Effect of dietary polyunsaturated phospholipid on the chemical composition of mesenteric lymph chylomicrons and the excretion of steroids into bile and feces in rat.

The effect of soybean phospholipid (SP) on the chemical composition of lymph chylomicrons and excretion of steroids into bile and feces was examined. Rats were meal-fed (9 am-10 am) or ad libitum-fed on diets containing phospholipid and neutral lipid (soybean oil or corn oil) for 2 weeks in order to assess the amount of chylomicrons secreted from the intestine during the absorption or post-absorption of dietary lipids. In meal-fed rats, dietary SP decreased the concentration of surface components (phospholipid, cholesterol and apoprotein A-I) of large chylomicrons and increased the core components (triglyceride) of small chylomicrons. In ad libitum-fed rats given SP, the concentration of triglyceride in small chylomicrons appeared to increase. Dietary SP increased the relative proportion of linoleic acid and decreased arachidonic acid at the 2-position of chylomicron-phospholipids. The calculated diameter of large and small chylomicron particles in meal-fed rats given SP increased and the particle number per ml lymph decreased compared to those values in rats given neutral lipid. The particle size of the small chylomicron in ad libitum-fed rats given SP also increased. Apoprotein A-I in lymph phosphate to microsomal membrane increased in the SP-fed rats. The excretion of neutral, but not acidic steroids into the bile and feces was increased in SP-fed rats.

Animals↗

Effect of dietary polyunsaturated phospholipid on the chemical composition of serum lipoproteins in rat.

The effect of soybean phospholipid (SP), given at the rate of 100/g/kg diet for 2-3 weeks, on the chemical composition of serum lipoprotein in rats was examined. Soybean oil (SO) containing almost comparable amounts of linoleic acid was used as a control diet. SP significantly decreased the concentration of serum cholesterol and apolipoprotein A-I (apo A-I) and increased apolipoprotein B (apo B). There was no significant change in the concentration of serum apolipoprotein E (apo E) and the other lipids. The reduction of cholesterol levels in all the lipoprotein fractions was observed. The reduction of the serum apo A-I was brought about by the addition of SP at the level of 1% while that of the cholesterol at the level of 4%. The subunit composition of apo A-I, but not apolipoprotein C, in high density lipoprotein (HDL) was also altered by SP. The high molecular weight of apo B was responsible for the increment of apoproteins in the low density lipoprotein (LDL). The triglyceride, but not the cholesterol ester, also increased in LDL. there was no significant difference between the groups in the fatty acid compositions of serum triglyceride and phospholipid. In the liver, SP significantly increased the concentration of cholesterol ester and decreased triglyceride. These results are discussed in the context of the role of the lipoprotein and apoprotein in the regulation of serum cholesterol concentration.

Animals↗