Dietary soybean protein moderates the deleterious disturbance of lipid metabolism caused by exogenous oxidized cholesterol in rats.

Effects of dietary protein on oxidized cholesterol-induced disturbance of lipid metabolism were examined in 4 week old male Sprague-Dawley rats, using casein and soybean protein as dietary protein source. The rats were given one of the two proteins in 0. 078% cholesterol (control), 0.25% cholesterol or 0.25% oxidized cholesterol mixture (containing 0.078% cholesterol) diets. Dietary oxidized cholesterol, compared to cholesterol, tended to inhibit hepatic sterol biosynthesis in casein-fed rats, whereas this inhibitory action was slightly moderated by intake of soybean protein. As a result, the hepatic 3-hydroxy-3-methylglutaryl-CoA reductase activity was rather higher in the rats fed oxidized cholesterol than in those fed cholesterol in the soybean protein-fed group. The hepatic cholesterol 7alpha-hydroxylase activity tended to be higher in the rats fed oxidized cholesterol than in those fed control diet in the soybean protein-fed group, despite the fact that oxidized cholesterol lowered the hydroxylase activity in the casein-fed group. On the other hand, dietary oxidized cholesterol tended to slightly enhance the hepatic Delta6 desaturase activity in the casein-fed group; however, this observation was not shown in the soybean protein-fed group. Moreover, dietary soybean protein facilitated fecal oxidized cholesterol excretion and simultaneously inhibited the accumulation of oxidized cholesterol in serum and liver. In conclusion, dietary soybean protein alleviated the deleterious actions of exogenous oxidized cholesterol on hepatic cholesterol and linoleic acid metabolism, although these efficacies were not necessarily significant. A great part of these moderations may be exerted by the specific hypocholesterolemic function of soybean protein, such as the stimulation of fecal oxidized cholesterol excretion, the change of hormonal release and modulation of lipoprotein catabolism.     

Adult sterol metabolism is not affected by a positive sterol balance in the neonatal Golden Syrian hamster

Dietary components impact metabolism early in life. Some of the diet-induced effects are long lasting and can lead to various adult-based diseases. In the current studies, we examined the short-term effects of dietary cholesterol on neonatal hepatic sterol metabolism and the long-term effects that those early-life diets had on sterol metabolism in adulthood. Neonatal hamsters began consuming solid food as a supplement to milk by 5 days of age; diets contained 0 or 2% added cholesterol (wt/wt). By 10 days of age, plasma and liver cholesterol concentrations were 3.2- and 2.5-fold greater, respectively, in the neonates fed cholesterol. Hepatic sterol synthesis rates were suppressed 65% in cholesterol-fed neonates compared with control neonates. By 20 days of age, plasma and liver cholesterol concentrations were still greater and sterol synthesis rates were now suppressed maximally in neonates fed cholesterol compared with control neonates. The expression level of an apolipoprotein B-containing lipoprotein receptor (low-density lipoprotein receptor-related protein) was greater and the mature form of the sterol regulatory element-binding protein-2 was similar in livers of 20-day-old control neonates compared with control neonates at 10 days of age. To test whether the change in sterol balance in the neonatal period had a lasting effect on hepatic sterol metabolism, all animals were weaned on a low-cholesterol diet. At 70 days of age, hepatic sterol synthesis rates, plasma lipoprotein and liver cholesterol concentrations, and bile acid pool sizes and compositions were measured. Sterol balance in the adults was similar between animals fed either diet early in life, as demonstrated by a lack of difference in any parameter measured. Thus, even though dietary cholesterol suppressed hepatic sterol synthesis rates dramatically in the neonatal hamster, the change has little impact on sterol balance later in life.     

Effect of dietary protein on cholesterol homeostasis in diabetic rats

Normal and streptozotocin (STZ)-diabetic rats were studied in order to examine the effects of altering the type of dietary protein on cholesterol homeostasis. Rats were fed a non-purified or a purified diet containing either casein or soybean protein. The results obtained on the specific aspects of lipid metabolism were remarkably similar in control rats fed the non-purified (Purina Lab Chow) diet or the purified diet with the soybean protein. However, most of the findings obtained with the above two groups were different from those obtained with rats fed the purified diet containing casein. In the latter group, plasma cholesterol was elevated following a 15-day feeding period as compared to the other two dietary groups. The excess plasma cholesterol in the casein-fed group was found in two lipoprotein fractions with densities of 1.023-1.045 g/ml and 1.045-1.086 g/ml, respectively. The latter lipoprotein fraction was also enriched with apolipoprotein E. The casein-fed animals also showed a lower fractional rate of plasma cholesterol esterification and an abnormal accumulation of cholesterol in the body despite inhibition of cholesterol synthesis in the liver and in the intestines. Twelve to 15 days after the induction of diabetes, plasma cholesterol increased to a similar extent in the rats on all three diets. However, the distribution of cholesterol among the lipoprotein fractions was markedly different. The percentage of cholesterol in fractions of d less than 1.086 g/ml was increased while that carried in the fraction of d 1.086-1.161 g/ml decreased in the rats fed the nonpurified diet and the casein diet. In contrast, there was no change in the distribution of lipoprotein cholesterol between the diabetic and the control rats fed the soybean protein diet. The hepatic synthesis of cholesterol was unaltered in diabetic rats fed the nonpurified diet and the purified diet with soybean protein, but was increased 2.4-fold in diabetic rats fed casein. Intestinal cholesterol synthesis was increased in all three dietary groups. The increase was highest in the rats fed casein and lowest in rats fed soybean protein. The rate of sterol synthesis in the kidneys was not significantly affected by the diet or diabetes. In all three dietary groups diabetes led to an abnormal accumulation of cholesterol in the body. This accumulation was highest in the casein-fed rats and lowest in those fed the soybean protein diet. The cholesterol content of the kidneys was markedly increased by dietary casein.(ABSTRACT TRUNCATED AT 400 WORDS)     

Evaluation of the contribution of dietary cholesterol to hypercholesterolemia in diabetic rats and of sitosterol as a recovery standard for cholesterol absorption

The contribution of dietary cholesterol to hypercholesterolemia in diabetic rats fed chow ad libitum was evaluated. Diabetes was induced with streptozotocin, and the intake, absorption, and subsequent tissue distribution of dietary cholesterol were measured. Absorption was measured as the difference between [3H]cholesterol intake and fecal 3H-labeled neutral sterol excretion, using both [14C]sitosterol (added to diet) and [14C]cholesterol (added to feces) as recovery markers. [3H]Cholesterol absorption was underestimated by 1-3% using [14C]sitosterol as a recovery standard, due to the 7-8% absorption of sitosterol. After 3 weeks of diabetes, rats were hyperphagic, thereby increasing dietary cholesterol intake 2-fold. [3H]Cholesterol absorption was significantly increased from 69% in controls to 78% in diabetics, whereas [14C]sitosterol absorption was unaffected. With increased dietary cholesterol intake and decreased whole body cholesterol synthesis (Diabetes. 1983. 32: 811-819), influx from diet equaled for exceeded influx from synthesis. The amounts of 3H-labeled neutral sterol recovered from the small intestine, periphery, and plasma were increased 3- to 4-fold in the diabetic rats. Furthermore, the degree of hypercholesterolemia in diabetic rats was directly related to the fraction of plasma cholesterol derived from the diet. We conclude that the 2.3-fold increase in absorbed dietary cholesterol resulting from hyperphagia and, to a lesser extent, from increased fractional absorption, contributes to the hypercholesterolemia of diabetic rats fed chow ad libitum.     

Dietary oxidized cholesterol decreases expression of hepatic microsomal triglyceride transfer protein in rats

The aim of this study was to compare the effects of dietary oxidized cholesterol and pure cholesterol on plasma and very low density lipoprotein (VLDL) lipids and on some parameters of VLDL assembly and secretion in rats fed two different dietary fats. Four groups of male growing Sprague-Dawley rats were fed diets containing pure or oxidized cholesterol (5 g/kg diet) with either coconut oil or salmon oil as dietary fat (100 g/kg diet) for 35 days. Rats fed oxidized cholesterol supplemented diets had significantly lower concentrations of triglycerides and cholesterol in plasma and VLDL than rats fed pure cholesterol supplemented diets irrespective of the type of fat. In addition, rats fed oxidized cholesterol supplemented diets had significantly lower relative concentrations of microsomal triglyceride transfer protein messenger ribonucleic acid (mRNA) than rats fed pure cholesterol supplemented diets. In contrast, hepatic lipid concentrations and the relative concentration of apolipoprotein B mRNA were not influenced by the dietary factors investigated. Parameters of hepatic lipogenesis (relative mRNA concentration of sterol regulatory element binding protein-1c and activity of glucose-6-phosphat dehydrogenase) were significantly reduced by feeding fish oil compared to coconut oil, but were not affected by the type of cholesterol. In conclusion, the data of this study suggest, that dietary oxidized cholesterol affects VLDL assembly and/or secretion by reducing the synthesis of MTP but not by impairing hepatic lipogenesis or synthesis of apolipoprotein B.     

Increased incorporation of dietary plant sterols and cholesterol correlates with decreased expression of hepatic and intestinal Abcg5 and Abcg8 in diabetic BB rats

The aim of this study was to determine the impact of dietary plant sterols and stanols on sterol incorporation and sterol-regulatory gene expression in insulin-treated diabetic rats and nondiabetic control rats. Diabetic BioBreeding (BB) and control BB rats were fed a control diet or a diet supplemented with plant sterols or plant stanols (5 g/kg diet) for 4 weeks. Expression of sterol-regulatory genes in the liver and intestine was assessed by real-time quantitative polymerase chain reaction. Diabetic rats demonstrated increased tissue accumulation of cholesterol and plant sterols and stanols compared to control rats. This increase in cholesterol and plant sterols and stanols was associated with a marked decrease in hepatic and intestinal Abcg5 (ATP-binding cassette transporter G5) and Abcg8 (ATP-binding cassette transporter G8) expressions in diabetic rats, as well as decreased mRNA levels of several other genes involved in sterol regulation. Plant sterol or plant stanol supplementation induced the accumulation of plant sterols and stanols in tissues in both rat strains, but induced a greater accumulation of plant sterols and stanols in diabetic rats than in control rats. Surprisingly, only dietary plant sterols decreased cholesterol levels in diabetic rats, whereas dietary plant stanols caused an increase in cholesterol levels in both diabetic and control rats. Therefore, lower expression levels of Abcg5/Abcg8 in diabetic rats may account for the increased accumulation of plant sterols and cholesterol in these rats.     

Hypolipidemic action of taurine in rats.

The effect of taurine on the serum and liver cholesterol and triglyceride levels was studied in rats fed cholesterol plus cholic acid. Four groups of 4 weeks old rats were fed control diet, hypercholesterolemic diet (HCD), HCD + 1% taurine or HCD + 2% taurine for 8 weeks. Addition of taurine in HCD diet showed a significant reduction not only in serum total cholesterol and triglyceride levels but also in liver total cholesterol, lipid and triglyceride contents compared to the animals fed HCD alone. Histological examination of organs of these animals showed severe fatty vacuolation in livers and signet ring type vacuolation in kidneys of rats fed HCD. Taurine showed ameliorating effect on these abnormalities. The animals fed taurine in HCD also showed increased bile and sterol excretion in faeces compared to rats fed HCD alone. Taurine showed significant hypocholesterolemia in rats probably by enhancing the catabolism of cholesterol and reducing the absorption of dietary cholesterol.     

Rates of sterol synthesis in the liver and extrahepatic tissues of the SHR/N-corpulent rat, an animal with hyperlipidemia and insulin-independent diabetes

The SHR/N-corpulent rat is a new genetically obese strain that exhibits both insulin-independent diabetes and hyperlipidemia. The present studies were undertaken to characterize various parameters of cholesterol metabolism in this model. At 11 weeks of age, the obese animals had markedly elevated plasma cholesterol, triglyceride, glucose, and insulin concentrations and elevated hepatic triglyceride concentrations compared to their lean littermates. The additional cholesterol in plasma was carried in the fractions of density less than 1.006, 1.020-1.055, 1.055-1.095, and 1.095-1.21 g/ml. In the obese rats the level of free cholesterol in the liver was decreased significantly while that of cholesteryl ester showed little change. Hepatic sterol synthesis was markedly suppressed in the obese animals. However, the rate of sterol synthesis in the small intestine and other extrahepatic tissues generally remained unchanged. Although hepatic synthesis was suppressed, whole animal sterol synthesis in the obese rats was similar to that in the lean controls. This resulted because, in the obese animals, not only was the reduced rate of hepatic synthesis partly balanced by a greater than 70% increase in liver mass, but the mass of the small intestine and adipose tissue was also increased more than 30% and 4-fold, respectively, thereby making these tissues quantitatively more important sites of sterol synthesis. When obese rats were pair-fed to the intake of their lean littermates for 10 weeks, there was only a modest reduction in body weight and plasma cholesterol concentration, and the rate of hepatic sterol synthesis remained very low. The suppression of synthesis in the liver also persisted when the obese rats were fed surfomer, a drug that specifically blocks cholesterol absorption. In contrast, feeding cholestyramine restored the rate of hepatic sterol synthesis to that found in lean animals. Bile acid pool size in the obese males and females was 2.5-fold greater than in their lean controls. The suppression of hepatic sterol synthesis in this model may be due to a change in the entero-hepatic circulation of bile acids arising from an expanded pool or, alternatively, it may represent a compensatory response to overproduction of sterol and its precursors in the intestinal and adipose compartments.     

Effects of saturated and unsaturated fats given with and without dietary cholesterol on hepatic cholesterol synthesis and hepatic lipid metabolism

Hepatic cholesterol synthesis was studied in rats after consuming diets of varying neutral lipid and cholesterol content. Cholesterol synthesis was evaluated by measuring 3-hydroxy-3-methylglutaryl-CoA reductase and by determining the rate of 3H-labeled sterol production from [3H]mevalonate. Results were correlated with sterol balance data and hepatic lipid content. Hepatic cholesterol synthesis was relatively great when cholesterol was excluded from the diet. The source of neutral dietary lipids, saturated vs. unsaturated, produced no change in hepatic sterol synthesis. Values for fecal sterol outputs and hepatic cholesterol levels were also similar in rats consuming either saturated or unsaturated fats. When 1% cholesterol was added to the diet, hepatic cholesterol synthesis was suppressed but the degree of suppression was greater in rats consuming unsaturated vs. saturated fats. This was associated with greater accumulation of cholesterol in livers from rats consuming unsaturates and a reduction in fecal neutral sterol output in this group as opposed to results from rats on saturated fats. Cholesterol consumption also altered the fatty acid composition of hepatic phospholipids producing decreases in the percentages of essential polyunsaturated fatty acids. It is concluded that dietary cholesterol alters cholesterol and fatty acid metabolism in the liver and that this effect is enhanced by dietary unsaturated fats.     

Sterol utilization in honey bees fed a synthetic diet: Analysis of prepupal sterols

The sterols of prepupal honey bees, Apis mellifera L., from brood reared by workers fed chemically-defined synthetic diets containing cholesterol, campesterol, sitosterol, stigmasterol, 24-methylenecholesterol, or no sterol over a 12-week period were isolated, identified, and quantified. The major sterol present in each prepupal sample was 24-methylenecholesterol, but significant levels of sitosterol and isofucosterol were also present in every case, as was a very small percentage of desmosterol (usually < 1%). This is the first report of isofucosterol being identified in the sterols of the honey bee. A considerably larger percentage of each dietary sterol was found in prepupae reared by workers fed that particular sterol in the diet. This was most dramatic in the case of the cholesterol diet in which case cholesterol content increased to as much as 17.2% of the prepupal sterols, whereas cholesterol had not exceeded 2.2% in samples from other diet regimens. However, stigmasterol comprised no more than 6.3% of the total sterols in any sample from prepupae fed the stigmasterol diet. The preponderance of 24-methylenecholesterol in all prepupae, regardless of the dietary sterol provided to the workers, as well as the lesser quantities of sitosterol and isofucosterol present in all samples, suggest a unique system of utilization and metabolism of these dietary sterols by the worker bees. Apparently they make available to the brood varying amounts of unchanged dietary sterol plus considerable and fairly constant portions of 24-methylenecholesterol, sitosterol, and isofucosterol drawn from their own sterol pools.     

Suppression of Plasma Cholesterol Elevation by Okara Tempe in Rats

Okara Tempe (OT), an Indonesian fermented traditional food, which is the fermented okara (insoluble residues of homogenized soybean, OC) by Rhizopus oligosporus, and which is interested in as a new high fiber and low energy soybean foodstuff. In this study, the effects of protein and dietary fiber (DF) of OT on sterol metabolism in rats were investigated. When rats were fed by OT or casein as protein source, the cholesterol and bile acid levels in plasma was significantly lower in OT fed group than in casein fed group. When rats were fed by OT or OC as DF source, in OT fed group, the cholesterol and bile acid levels in plasma was similar to them in OC fed group, but the cholesterol level in liver was lower than it in OC fed group, and the excretion of cholesterol and bile acid in feces was larger than in OC fed group. These results suggest that the cholesterol lowering action of OT in plasma would arise from the complementary action of protein and water soluble DF in OT.     

The Effects of Dietary Iron and Capsaicin on Hemoglobin,Blood Glucose,Insulin Tolerance,Cholesterol, and Triglycerides,in Healthy and Diabetic Wistar Rats

ObjectiveOur aim was to assess the effects of dietary iron, and the compound capsaicin, on hemoglobin as well as metabolic indicators including blood glucose, cholesterol, triglycerides, insulin, and glucose tolerance.ResultsHealthy rats fed a low-iron diet exhibited significantly reduced total cholesterol and triglyceride levels, compared with rats fed a control diet. Significantly reduced blood lipid was also provoked by low dietary iron in diabetic rats, compared with those fed a control diet. Insulin, and glucose tolerance was only improved in healthy rats fed the low-iron diet. Significant increases in total cholesterol were found in diabetic rats fed a high-iron diet, compared with healthy rats fed the same diet, although no statistical differences were found for triglycerides. Hemoglobin levels, which were not statistically different in diabetic versus healthy rats fed the high-iron diet, fell when capsaicin was added. Capsaicin also provoked a fall in the level of cholesterol and triglycerides in diabetic animals, versus diabetics fed with the high iron diet alone. In conclusion, low levels of dietary iron reduced levels of serum triglycerides, hemoglobin, and cholesterol, and significantly improved insulin, and glucose tolerance in healthy rats. In contrast, a high-iron diet increased cholesterol significantly, with no significant changes to triglyceride concentrations. The addition of capsaicin to the high-iron diet (for diabetic rats) further reduced levels of hemoglobin, cholesterol, and triglycerides. These results suggest that capsaicin, may be suitable for the treatment of elevated hemoglobin, in patients.     

Improving Effect of Dietary Taurine on Marked Hypercholesterolemia Induced by a High-cholesterol Diet in Streptozotocin-induced Diabetic Rats

The effect of dietary taurine on hypercholesterolemia induced by a high-cholesterol diet in streptozotocin (STZ)-induced diabetic rats was investigated. The concentrations of serum and liver cholesterol were markedly elevated in STZ-diabetic rats fed on the cholesterol-containing diet, and dietary taurine significantly reduced this elevated level of cholesterol in the serum and liver. The gene expression of cholesterol 7α-hydroxylase (CYP7A1), which is the rate-limiting enzyme for cholesterol degradation, was induced by the supplementation of taurine to the high-cholesterol diet. It is suggested that one of the reasons for this hypocholesterolemic action by taurine might have been the enhancement of cholesterol degradation.     

Dietary cholesterol utilization by the housefly,Musca domestica

The amount of cholesterol and the distribution of its metabolites were studied in various larval tissues of the housefly (Musca domestica), reared on a high cholesterol diet containing the radioactive cholesterol. The sterol content was also examined in adults derived from larvae reared on increasing dietary cholesterol concentration in separate batches. The results suggest that when the dietary sterol concentration was raised from 0.002 to 0.02% wet weight (an optimal concentration required for a maximal growth and development of insect), the sterol content of six-day old larvae was increased approx. 4-fold. However, a further 10-fold increase of dietary cholesterol (to 0.22% of wet weight) was associated with only a 1.5-fold increase in larval sterol content, and no increase in the sterol content of adult insects derived from such larvae was observed. This increase of sterol content of whole larvae was found to be confined to the larval cuticle and composite gut fractions and may be attributed to unabsorbed cholesterol in the gut, and to a solubilizing effect of the cuticle. These findings suggest that when the cholesterol requirement for the maximal growth of the insect has been reached, larvae are able to regulate the intake of ingested cholesterol, and no more is taken up through the gut even when a high gut concentration of cholesterol is present.The adults contained a higher percentage of esterified sterols than the larvae, approx. 25% of the sterol in females and 14% of sterol in males were esterified.     

Role of the intestinal brush border in the absorption of cholesterol in rats

1. Short-term incubation of the everted intestinal sacs of rats in media containing cholesterol oleate or cholesterol plus oleic acid resulted in rapid hydrolysis, but no synthesis, of the sterol ester. 2. On separation of the brush border from the rest of the mucosal cell, almost all of the hydrolytic activity and appreciable amounts of the synthetic activity of the whole cell were found to be present in the brush-border fraction. 3. The isolated brush-border fraction contained considerable amounts of cholesterol, which was always present in the unesterified state; the rest of the cell contained about an equal amount of unesterified cholesterol, but, in addition, small but definite amounts of the esterified sterol were also found in this fraction. 4. On feeding rats with [4-(14)C]cholesterol, which was diluted with 3mg. of cholesterol, it was found that the brush border very rapidly took up the fed sterol without changing its net content of cholesterol. No traces of radioactive cholesterol ester could ever be detected in the isolated brush border after feeding with (14)C-labelled esterified or unesterified cholesterol. 5. The appearance of the labelled sterol was quite rapid in the rest of the cell also, where small proportions were found in the esterified state. 6. Therefore the sequence of events in the absorption of cholesterol appears to be: the dietary cholesterol esters are hydrolysed by the cholesterol ester hydrolase of pancreas or of the mucosal brush border or both, after which the brush border rapidly absorbs the de-esterified sterol and transfers it into the mucosal cell, by a mechanism of displacement, where it is slowly re-esterified for transport through the lymph.     

Distribution and dynamic state of sterols and steroids in the tissues of an insect, the roach Eurycotis floridana

The total concentrations of sterols in the tissues of the roach, Eurycotis floridana, reared under aseptic conditions and on semisynthetic diets, are similar to, but somewhat lower than, those of tissues of vertebrates. Total concentrations of tissue sterols are relatively independent of dietary concentration of sterols whether the diet contains 0.1% cholesterol as the sole sterol, or a "minimal cholesterol" mixture (0.1% cholestanol together with 0.005% cholesterol). Under the latter conditions the cholesterol is incorporated preferentially into most tissues and remains almost exclusively unesterified, while the cholesterol-sparing sterol is esterified to varying degree, depending upon the tissue. The turnover of tissue sterols has been studied. Cholesterol of the tissues of adult insects grown on a diet containing this sterol alone may be displaced by cholestanol fed as 5% of the total diet, initially at an appreciable rate but later much less rapidly. In growing insects that have received a diet containing cholestanol together with minimal cholesterol, the unesterified cholesterol turns over slowly in all tissues and immeasurably slowly in some. The unesterified sparing sterol, on the other hand, turns over at a much greater rate. The turnover of sterols during growth is accompanied by a shift of sterols from the unesterified to the esterified pool in all tissues. The fat body of the growing insect stores sterols (apparently as their esters) that have been displaced from other tissues. The fat body of the adult does not show evidence of sterol storage. Polar derivatives of sterols are present in minor amount in all tissues of the insect, most abundantly in the mid-intestine and gastric caeca. These compounds seem likely to be C(27) steroids.     

Improving effect of dietary taurine on marked hypercholesterolemia induced by a high-cholesterol diet in streptozotocin-induced diabetic rats

The effect of dietary taurine on hypercholesterolemia induced by a high-cholesterol diet in streptozotocin (STZ)-induced diabetic rats was investigated. The concentrations of serum and liver cholesterol were markedly elevated in STZ-diabetic rats fed on the cholesterol-containing diet, and dietary taurine significantly reduced this elevated level of cholesterol in the serum and liver. The gene expression of cholesterol 7 alpha-hydroxylase (CYP7A1), which is the rate-limiting enzyme for cholesterol degradation, was induced by the supplementation of taurine to the high-cholesterol diet. It is suggested that one of the reasons for this hypocholesterolemic action by taurine might have been the enhancement of cholesterol degradation.     

Hypocholesterolemic effect of rice protein is due to regulating hepatic cholesterol metabolism in adult rats

Aging is one of major risk factors for developing hypercholesterolemia. To elucidate the cholesterol-lowering mechanism exerted by rice protein (RP), the effects on hepatic cholesterol outputs and cholesterol metabolism related enzymes were investigated in adult rats, which were fed by casein (CAS) and RP without cholesterol in diets. After 2 weeks of feeding, the significant cholesterol-lowering effect was observed in adult rats fed by RP compared to CAS. The hepatic total- and VLDL-cholesterol secretions into circulation were significantly depressed in RP group, whereas biliary outputs of bile acids and cholesterol were effectively stimulated by RP-feeding, causing an increase in fecal sterol excretion compared to CAS. As a result, the apparent cholesterol absorption was significantly inhibited by RP. RP-feeding significantly increased the activity and gene expression of cholesterol 7α-hydroxylase, whereas acyl-CoA:cholesterol acyltransferase-2 activity and gene expression were significantly decreased by RP as compared with CAS. Neither activity nor gene expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase of RP did differ from CAS in the liver. The present study demonstrates that rice protein can prevent hypercholesterolemia through modifying hepatic cholesterol metabolism under cholesterol-free dietary condition. The findings suggest that hypocholesterolemic action induced by rice protein is attributed in part to the inhibition of cholesterol absorption during the adult period.     

Differential effects of polyunsaturated fatty acids on sterol synthesis rates in adult and fetal tissues of the hamster: consequence of altered sterol balance

Cholesterol is necessary for the proper growth and development of the fetus. Consequently, disruptions in cholesterol biosynthesis lead to abnormal fetal development. It has been shown that in cells exposed to polyunsaturated fatty acids (PUFA), the expressions of genes and activities of enzymes involved in cholesterol synthesis are reduced. Similarly, we found that adult male hamsters fed PUFA-enriched diets had an approximately 60% reduction in in vivo hepatic sterol synthesis rates. If fetal tissues respond to PUFA in the same manner as do adult livers, then maternal dietary PUFA could lead to a reduction in fetal sterol synthesis rates and possibly abnormal development. To investigate the impact of maternal dietary fatty acids on fetal sterol synthesis rates, female hamsters were fed diets enriched in various fatty acids before and throughout gestation. In vivo sterol synthesis rates were measured in fetuses at mid- and late gestation. At both gestational stages, dietary PUFA had no effect on fetal sterol synthesis rates. This lack of effect was not a consequence of a lack of PUFA enrichment in fetal fatty acids or the lack of PUFA receptor expression in the fetus. We hypothesize that the fetus may experience a dysregulation of sterol synthesis as the result of the fetus being in a negative sterol balance; the PUFA-induced suppression of sterol synthesis in the adult male hamster liver was ablated by creating a net negative sterol balance across the adult hepatocyte.     

Prune suppresses ovariectomy-induced hypercholesterolemia in rats

Elevated cholesterol among women who have experienced natural or surgical menopause has been linked to ovarian hormone deficiency. The purpose of this study was to investigate the efficacy of prune, a good source of dietary fiber and phytochemicals, on lowering cholesterol in an ovariectomized (ovx) rat model. Forty-eight 90-day-old female Sprague-Dawley rats were randomly assigned to four groups: sham-operated (sham) + control diet, ovx + control diet, ovx + low-dose (LD; 5%) prune, and ovx + high-dose (HD; 25%) prune. After 45 days of treatment, rats were euthanized and tissues were collected for analyses. Ovariectomy elevated serum total cholesterol by 22% compared with sham, and HD prune diet prevented this increase without affecting high density lipoprotein cholesterol concentrations. Animals fed the HD prune diet had 13% lower liver total lipids compared with ovx animals. The findings of this study showed that prune exhibits hypocholesterolemic properties in ovarian hormone deficiency. Dose-response studies should be conducted to establish the effectiveness of prune in prevention of hypercholesterolemia in postmenopausal women who are not on estrogen replacement therapy and seek dietary alternatives. Mechanistic studies also are needed to establish its mode of action.