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Biomedical subjects

M Sugano

Publications and source records attributed to M Sugano.

At least 217 records · Page 12Linked to original sources

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.

Aging↗

Influence of dietary cis and trans fats on DMH-induced colon tumors, steroid excretion, and eicosanoid production in rats prone to colon cancer.

The effect of geometrical isomerism of dietary fats on colon tumorigenesis was studied in male and female rats of a strain prone to colon cancer (Wistar-Furth-Osaka). The rats were fed purified diets containing either partially hydrogenated corn oil (trans fat) or high-oleic safflower (cis fat) at the 5% level for one week and received a single oral dose of 1,2-dimethylhydrazine. The difference in the fatty acid composition of dietary fats was confined solely to the geometry of octadecenoate. An appropriate level of linoleic acid (2% of total energy) was supplied. After about 60 weeks, neither fat-type nor sex-dependent differences in the incidence of colon and small intestinal tumors was observed. The fecal excretion of neutral but not acidic steroids was higher in male rats fed the trans fat than in those fed the cis fat, but the composition remained almost unchanged. Aortic production of prostacyclin and the plasma concentration of thromboxane B2 were not influenced by dietary fats, although these were significantly higher in females, irregardless of the fat source. Thus, trans fat behaved much like the cis fat in various parameters, except for steroid excretion.

Animals↗

Interrelated effects of dietary fiber and fat on lymphatic cholesterol and triglyceride absorption in rats.

Lymph cannulated rats were administered intragastrically a test emulsion containing 25 mg of [14C]cholesterol, 50 mg of either guar gum, cellulose or chitosan, and 200 mg of either safflower, high-oleic safflower or palm oil, and the absorption of labeled cholesterol and fatty acids was measured. The type of both dietary fiber (P less than 0.001) and fat (P less than 0.05) significantly influenced cholesterol absorption. A significant interaction of fiber and fat on cholesterol absorption (P less than 0.05) was also observed. Chitosan effectively lowered cholesterol absorption more than did guar gum or cellulose, and this effect was more significant when given with safflower or high-oleic safflower oil than with palm oil. When guar gum was the source of dietary fiber, dietary fats did not modify cholesterol absorption. Dietary fiber also significantly affected triglyceride absorption (P less than 0.05). Absorption tended to be low in the chitosan, high in the cellulose and intermediate in the guar gum group. Absorption of safflower and high-oleic safflower oils tended to be higher than that of palm oil when cellulose or guar gum was fed. Guar gum, as compared with the other fibers, altered the absorption pattern of both cholesterol and triglyceride. The results showed that the type of dietary fat significantly influenced the effect that dietary fiber exerted on lipid absorption.

Animals↗

The interrelated effects of n-6/n-3 and polyunsaturated/saturated ratios of dietary fats on the regulation of lipid metabolism in rats.

The effects of various n-6/n-3 (0.45-9.31) and polyunsaturated/saturated (P/S; 0.25-6.08) ratios of dietary fatty acids on various lipid parameters were studied in rats using a combination of palm oil, safflower oil, soybean oil and perilla oil. When the n-6/n-3 ratio was changed while maintaining a constant P/S ratio (1.2), the concentration of serum cholesterol tended to increase linearly with the increasing n-6/n-3 ratio, whereas liver cholesterol tended to decrease. Serum triglyceride level increased linearly up to a n-6/n-3 ratio of approximately 5, whereas liver triglyceride was not influenced. When the n-6/n-3 ratio was kept relatively constant (5.6-6.4), serum and liver cholesterol levels decreased up to a P/S ratio of approximately 2, whereas serum triglyceride tended to be low below this value. The ratio of arachidonate to linoleate in tissue phosphatidylcholine (PC) was also influenced by the n-6/n-3 and P/S ratios; it increased up to a n-6/n-3 ratio of approximately 4, whereas it decreased up to a P/S ratio of approximately 2. The percentage of eicosapentaenoic and docosahexaenoic acid (n-3) in tissue phosphatidylcholine was positively related to dietary n-3 fatty acid levels. Prostacyclin (PGI2) production by thoracic aorta reached a plateau at a n-6/n-3 ratio approximately 5, whereas it tended to decrease with an increasing P/S ratio. Platelet production of thromboxane A2 exhibited a parabola-like pattern with a peak value at a n-6/n-3 ratio of approximately 2, whereas it was independent of the P/S ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

Effects of addition of sulfur-containing amino acids and glycine to soybean protein and casein on serum cholesterol levels of rats.

The effects of the supplementation of methionine (Met), cystine (Cys), and glycine (Gly) to soybean protein or casein on serum and liver lipid levels were studied in rats. Rats were fed cholesterol-free diets containing 25% soybean protein or casein supplemented with 0.75% Met, 2.5% Gly, or a combination of these two for 4 weeks. The addition of Met to soybean protein caused a significant increase in serum cholesterol and this was slightly ameliorated when Gly was given simultaneously. In rats fed casein diets, serum cholesterol tended to decrease when Gly, or Met and Gly were added. A simultaneous supplementation of Met and Gly to casein resulted in a reduction of hepatic cholesterol. Cystine added at the 0.6% level did not cause demonstrable changes in lipid concentrations except for a drop in serum triglyceride of the casein group. When 2.0% Gly was added to cholesterol-enriched diets containing 20% protein, serum cholesterol decreased significantly only when the protein source was casein and the level attained was comparable to that observed in rats fed soybean protein. Liver cholesterol was also markedly decreased by the addition of Gly to casein. The results suggest a possible role of Gly in the regulation of serum cholesterol levels by dietary protein.

Animals↗

Effects of sitosterol and sitostanol on micellar solubility of cholesterol.

The influence of sitosterol and sitostanol on the solubility of cholesterol in mixed bile salt micelles in vitro and in vivo was investigated to examine the mechanism by which sitostanol inhibits cholesterol absorption more than does sitosterol. Both sitosterol and sitostanol decreased micellar solubility of cholesterol to a similar extent, when determined with the turbidity. Also, these sterols reduced the concentration of cholesterol in micelles, both in vitro and in vivo. The extent of the reduction of micellar solubility of cholesterol by these sterols was almost the same in vitro, whereas sitostanol tended to reduce the solubility more effectively than sitosterol in vivo. Thus, the interference with cholesterol solubilization in vivo may be responsible for effective inhibition of cholesterol absorption by sitostanol. Since the effect of sitostanol was not observed in vitro, there is a possibility that another factor(s) not included in the in vitro system might affect the action of sitostanol on micellar solubility of cholesterol in vivo.

Animals↗

Transient control of serum cholesterol homeostasis in adult ExHC (exogenous hypercholesterolemic) rats by dietary cholesterol during weanling period.

Rats hyper-responsive to a diet containing cholesterol plus cholic acid (exogenous hypercholesterolemic (ExHC) rats) were used to assess if cholesterol feeding at weanling period influences later serum cholesterol homeostasis. Diets containing cholesterol plus cholic acid (atherogenic diet) in early life, when compared to non-atherogenic diet, caused a transient suppression of serum cholesterol elevation in very-low- and low-density lipoprotein fractions during refeeding of the atherogenic diet in later life. Such an effect was not observed when ExHC rats were early given a diet supplemented with cholesterol or cholic acid alone, nor when ordinary Sprague-Dawley rats were given atherogenic diet. Early atherogenic diet caused an increased secretion of cholesterol as very-low-density lipoprotein from the perfused livers of adult ExHC rats. Neither the activity of hepatic cholesterol-7 alpha-hydroxylase of fecal steroid excretion in later life was influenced by the early dietary manipulation. Therefore, the present results show the deferred effect of early dietary manipulation on later serum cholesterol metabolism in ExHC rats, but the underlying mechanism(s) remains to be determined.

Animals↗

[Effect of oral-adsorbent (AST-120) in chronic renal failure (CRF) in rats].

The progression of renal failure has been suggested to be altered by dietary manipulation of protein based on the presumption that the progressive nature of CRF may be caused by the vicious cycle driven by some toxic metabolite uncleared by failing kidney. We studied 29 female Sprague-Dawley rats aged 12 weeks weighing 226 to 290 gm subjected to a 5/6 nephrectomy. 2 days after, group C (16 rats) were given a commercially prepared diet (CE-2, Japan Kurea). While group A (13 rats) were given the same diet and 5% AST-120. Initial serum creatinine of both group was 2.2 mg/dl. After 9 weeks, all surviving rats were sacrificed for evaluation of renal histology. During the observation period, survival rate, Ccr, urinary creatinine and urea excretion were significantly better in group A rats. Result also showed a better weight increase with concomitant increase in protein catabolic rate in group A rats. These result showed the beneficial effect of AST-120 in uremic rats in terms of survival rate and delaying the progression of CRF despite the presence of increased protein catabolic rate. Based on this study, one way of preventing the progression of renal failure is through removal of some toxic metabolite in the gastrointestinal tract by the use of oral adsorbent as exemplified by AST-120.

Age Factors↗

Age-related changes in lipid metabolism in rats: the consequence of moderate food restriction.

Male Sprague-Dawley rats, 3 weeks of age, received one of the four following dietary manipulations until 9 months of age: group AD, fed ad libitum; group R, restricted to 75% of food intake of group AD; group RAD, restricted until 5 months of age and then fed ad libitum; group ADR, fed ad libitum until 5 months of age and then restricted. The concentration of serum total and HDL cholesterol tended to be higher in group AD than in all groups that had experienced food restriction. Liver cholesterol was higher in groups AD and RAD than in groups R and ADR. Activity of hepatic microsomal hydroxymethylglutaryl-CoA reductase was comparable, whereas sterol synthesis from mevalonate was significantly higher in groups R and ADR than in groups AD and RAD. Cholesterol 7 alpha-hydroxylase activity also tended to be higher in groups R and ADR. It seems likely that hepatic cholesterol homeostasis functions effectively even when moderate food restriction was started after the growing period. In addition, food restriction reduced the ratio of arachidonate to linoleate, suggesting inhibition of the desaturation system.

Aging↗

Hypocholesterolemic action of chitosans with different viscosity in rats.

The relationship between hypocholesterolemic efficacy and average molecular weight of chitosan was studied in rats fed a cholesterol-enriched (0.5%) diet. Several chitosan preparations with a comparable degree of deacetylation but differing widely in average molecular weight, as demonstrated by viscosity, almost completely prevented the rise of serum cholesterol at the 5% dietary level. At the 2% level, chitosans with viscosities at both extremes exerted a comparable cholesterol-lowering action. The glucosamine oligomer composed mainly of three to five aminosugar residues was not effective. The results indicate that the hypocholesterolemic action of chitosans is independent of their molecular weight within the tested viscosity range.

Animals↗

The hypocholesterolemic action of the undigested fraction of soybean protein in rats.

Soybean protein was exhaustively digested with endo- and exo-type microbial proteases and the effect of the digestible low molecular fraction (LMF) and the undigested high molecular fraction (HMF) on the serum cholesterol level was compared to that of the intact protein in rats given a cholesterol-enriched diet. The HMF, peptides relatively abundant in hydrophobic amino acids, was found to be substantially hypocholesterolemic when fed at the nitrogen level equivalent to that of the 20% soybean protein diet, and not only serum but also liver cholesterol levels were similar to those usually encountered in rats given diets free of cholesterol. There was a dose-dependent reduction of serum and liver cholesterol when casein was replaced stepwise with HMF. The cholesterol-lowering action could be attributable to an increased fecal steroid excretion.

Animals↗

Sex-difference in the age related change of cholesterol metabolism in rats.

In Sprague-Dawley rats at the ages of 5 weeks (young) and 9 months (adult), the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase in age-matched animals was significantly higher in females than in males. The magnitude of the age-related decrease in the reductase activity was also greater in female rats. When rats were fed a cholesterol-enriched (1%) diet for 30 h as cholesterol challenge, the reduction of reductase activity depended more on sex than on age. The activity of cholesterol 7 alpha-hydroxylase was also higher in female than in male rats and it apparently remained unchanged with age in female rats while it decreased in male rats. With a cholesterol-enriched diet, the hydroxylase exhibited a significant age- and sex-dependent difference and it increased only in young males and adult females. In male rats, the concentration of hepatic cholesterol was significantly higher in adult than in young rats while it was comparable in female rats. The increase in hepatic cholesterol with dietary cholesterol was observed only in male adult rats. A significant age-related difference was observed in the concentration of serum cholesterol. The results suggest an existence of sex-dependent compensatory mechanism for maintenance of hepatic cholesterol homeostasis with age.

Aging↗

Protein-fat interaction on serum cholesterol level, fatty acid desaturation and eicosanoid production in rats.

The combined effects of dietary protein (casein or soybean protein) and fat (palm olein or mold oil) on several lipid parameters were studied in rats. The fatty acid composition of the dietary fats was made comparable except for the proportions of polyunsaturated fatty acids; mold oil contributed gamma-linolenic acid (GLA) at the expense of a portion of the linoleic acid in palm olein. When animals were fed casein rather than soybean protein, serum cholesterol levels were higher irrespective of the fat source, but it took a longer time to produce a significant difference when the dietary fat was mold oil. Soybean protein increased fecal steroid excretion, and mold oil tended to stimulate the excretion of neutral steroids. The ratio of arachidonate to linoleate in phosphatidylcholine from plasma, liver and thoracic aorta was markedly higher in the casein than in the soybean protein groups. Mold oil predictably improved a reduction of arachidonate by vegetable protein. The aortic production of prostacyclin was higher with mold oil than with palm olein irrespective of the protein source, although there was a trend toward a higher production with casein. No protein-fat interaction was observed on the concentration of plasma thromboxane B2. Thus GLA effectively modified metabolic consequences of dietary protein.

Adipose Tissue↗

Effects of dietary alpha- and gamma-linolenic acid on lipid metabolism in young and adult rats.

The effect of age on lipid metabolism was studied in rats fed diets containing safflower oil (SFO, 78% linoleic acid), evening primrose oil (EPO, 9.4% gamma-linolenic acid and 70% linoleic acid) or the mixture of safflower and linseed oil (SLO, 10.2% alpha-linolenic acid and 68% linoleic acid). The activity of hepatic HMG-CoA reductase declined with age in all groups. In adult rats, the reductase activity was high in the EPO group and low in the SLO group. The activity of hepatic cholesterol 7 alpha-hydroxylase was independent of the diet or age. Hepatic delta 6-desaturase activity was low in adult rats fed EPO. In liver microsomal phospholipids, the percentage of 22:5 n-6 decreased while that of 22:6 n-3 increased with age. The ratio of linoleate metabolites to linoleate was high in the EPO group and low in the SLO group. Liver and serum cholesterol increased with age only in rats fed the SLO diet. Thus, the results indicated an enhanced susceptibility to dietary fats with age.

Aging↗

Effects of various combinations of omega 3 and omega 6 polyunsaturated fats with saturated fat on serum lipid levels and eicosanoid production in rats.

The effects of varying the ratio of polyunsaturated/saturated fatty acids (P/S) and omega 3/omega 6 polyunsaturated fatty acids (PUFA) of dietary fats on lipid metabolism were studied in rats using safflower oil (SFO), linseed oil (LSO), palm oil (PLO), and a 1:1 combination of these oils. The hypocholesterolemic and hypotriglyceridemic effects depended on the P/S ratio of dietary fats, LSO (omega 3 PUFA) being more effective than SFO (omega 6 PUFA). A similar pattern of the response was observed on liver cholesterol and triglyceride. The liver cholesterol-lowering effect of LSO, but not SFO, remained even when they were combined with PLO. The activity of liver delta 6-desaturase tended to be higher while that of liver phospholipase A2 was significantly lower in the LSO group than in the SFO or PLO groups. The aortic PGI2 production and the production by platelets of thromboxane A2 were significantly low in rats fed LSO accompanying a distinct reduction of arachidonate in tissue phospholipids. The depressing effect of LSO disappeared when it was combined with SFO but not with PLO. There were no significant differences in enzyme activities and eicosanoid production between SFO and PLO in spite of a large difference in their P/S ratio. Thus, lipid parameters examined were complicatedly regulated by the ratios of omega 3/omega 6 as well as P/S, suggesting an existence of an appropriate ratio for these variables.

Animals↗

Cholesterol levels and eicosanoid production in rats fed phosphatidylinositol or soybean lecithin.

Male young rats were fed 8% corn oil diets supplemented either with 2% phosphatidylinositol (PI) from safflower seeds or soybean lecithin (SL) for 22 days. Other groups of rats were fed 10% corn oil diets with or without (control) 0.3% inositol (IN, equivalent to the inositol moiety of the PI diet). The plasma cholesterol level was low in the SL group whereas liver triglyceride was low in all supplemented groups. The aortic production of prostacyclin tended to be high in rats fed the control diet and low in rats fed the SL diet, the PI and IN groups being intermediate. The concentration of plasma thromboxane B2 was comparable among various groups. In plasma and liver phosphatidylcholine, the ratio of arachidonate/linoleate was low in rats fed SL and high in rats fed PI or IN diets. The results indicate that, in addition to SL, the inositol moiety of PI may have a significant role in the regulation of lipid metabolism.

Adipose Tissue↗

Morphological evaluation of the atherogenicity of corn oil, hydrogenated corn oil, and butter fat in quail.

The atherogenicity of corn oil, hydrogenated corn oil, and butter fat was studied using 57 fourty-day-old male Japanese quails. The animals were fed one of the following diets: basal diet, basal diet with corn oil plus cholesterol, basal diet with hydrogenated corn oil plus cholesterol, or basal diet with butter fat plus cholesterol. Each atherogenic diet contained 15% fat and 2% cholesterol. Marked hypercholesterolemia developed in all fat-fed groups after 3 weeks or 3 months, but no significant difference was seen among the groups. The degree of the luminal narrowing of the ascending aorta and brachiocephalic arteries was highest in the corn oil group and lowest in the hydrogenated fat group. Ultrastructurally, all the fat-fed groups showed similar cellular changes in their aortic lesions. The major cell type of the thickened intima was fibroblast-like cells with or without lipid droplets. Immunohistochemical studies disclosed that alpha-1-antichymotrypsin was strongly positive for fibroblast-like cells in the thickened intima, whereas it was negative for those in the tunica media of the ascending aorta and its branches. These data suggest that hydrogenated corn oil has a less potent stimulating effect on the thickening of the arterial intima than corn oil and butter fat.

Animals↗

Inhibition of cholesterol absorption in rats by plant sterols.

The extent and site(s) of inhibition of cholesterol absorption by plant sterols, sitosterol and fucosterol, were studied in rats. The intragastric administration of a single emulsified lipid meal containing 25 mg [3H]cholesterol and 25 mg of either sitosterol or fucosterol inhibited the lymphatic absorption of cholesterol by 57% and 41%, respectively, in 24 hr. Less than 2% of each plant sterol was absorbed in the 24-hr period. In contrast, neither plant sterol (50 microM) inhibited cholesterol absorption when co-administered with equimolar amounts of cholesterol in phospholipid-bile salt micelles nor was either absorbed from the micellar solution. A series of in vitro studies was conducted to identify the site(s) of plant sterol inhibition of cholesterol absorption and to account for the difference in inhibitory effectiveness of sitosterol and fucosterol. A comparison of the micellar solubility of each sterol alone and in equimolar binary mixtures (to 2.0 mM) revealed that the solubility of individual sterols decreased in the following order: cholesterol, fucosterol, sitosterol, and that in binary mixtures cholesterol solubility was decreased by sitosterol and, to a lesser extent, by fucosterol relative to its solubility alone. A comparison between micellar-solubilized cholesterol and either sitosterol or fucosterol for binding to isolated brush border membranes, intestinal mucin, or for esterification by either cholesterol esterase or acyl coenzyme A:cholesterol acyltransferase revealed moderate to no competition. The data suggest that plant sterols displace cholesterol from bile salt (taurocholate) micelles and that sitosterol is more effective than fucosterol in this capacity.

Absorption↗