Structured triglycerides containing caprylic (8:0) and oleic (18:1) fatty acids reduce blood cholesterol concentrations and aortic cholesterol accumulation in hamsters

The effects of structured triglycerides containing one long chain fatty acid (oleic acid, C18:1) and one short chain saturated fatty acid (caprylic acid, 8:0) on lipidemia, liver and aortic cholesterol, and fecal neutral sterol excretion were investigated in male Golden Syrian hamsters fed a hypercholesterolemic regimen consisting of 89.9% commercial ration to which was added 10% coconut oil and 0.1% cholesterol (w/w). After 2 weeks on the HCD diet, the hamsters were bled, following an overnight fast (16 h) and placed into one of three dietary treatments of eight animals each based on similar plasma cholesterol levels. The hamsters either continued on the HCD diet or were placed on diets in which the coconut oil was replaced by one of two structured triglycerides, namely, 1(3),2-dicaproyl-3(1)-oleoylglycerol (OCC) or 1,3-dicaproyl-2-oleoylglycerol (COC) at 10% by weight. Plasma total cholesterol (TC) in hamsters fed the OCC and COC compared to the HCD were reduced 40% and 49%, respectively (P<0.05). Similarly, hamsters fed the OCC and COC diets reduced their plasma nonHDL cholesterol levels by 47% and 57%, respectively (P<0.05), compared to hamsters fed the HCD after 2 weeks of dietary treatment. Although hamsters fed the OCC (-26%) and COC (-32%) had significantly lower plasma HDL levels compared to HCD, (P<0.05), the plasma nonHDL/HDL cholesterol ratio was significantly lower (P<0.05) compared to the HCD for the OCC-fed (-27%) and the COC-fed (-38%) hamsters, respectively. Compared to the HCD group, aortic esterified cholesterol was 20% and 53% lower for the OCC and COC groups, respectively, with the latter reaching statistical significance, P<0.05. In conclusion, the hamsters fed the structured triglyceride oils had lower blood cholesterol levels and lower aortic accumulation of cholesterol compared to the control fed hamsters.     

Different palm oil preparations reduce plasma cholesterol concentrations and aortic cholesterol accumulation compared to coconut oil in hypercholesterolemic hamsters

Several studies have reported on the effect of refined, bleached and deodorized palm oil (RBD-PO) incorporation into the diet on blood cholesterol concentrations and on the development of atherosclerosis. However, very little work has been reported on the influence of red palm oil (RPO), which is higher in carotenoid and tocopherol content than RBD-PO. Thus, we studied the influence of RPO, RBD-PO and a RBD-PO plus red palm oil extract (reconstituted RBD-PO) on plasma cholesterol concentrations and aortic accumulation vs. hamsters fed coconut oil. Forty-eight F1B Golden Syrian hamsters (Mesocricetus auratus) (BioBreeders, Watertown, MA) were group housed (three/cage) in hanging polystyrene cages with bedding in an air-conditioned facility maintained on a 12-h light/dark cycle. The hamsters were fed a chow-based hypercholesterolemic diet (HCD) containing 10% coconut oil and 0.1% cholesterol for 2 weeks at which time they were bled after an overnight fast and segregated into four groups of 12 with similar plasma cholesterol concentrations. Group 1 continued on the HCD, Group 2 was fed the HCD containing 10% RPO in place of coconut oil, Group 3 was fed the HCD containing 10% RBD-PO in place of coconut oil and Group 4 was fed the HCD with 10% reconstituted RBD-PO for an additional 10 weeks. Plasma total cholesterol (TC) and non-high-density lipoprotein-cholesterol (HDL-C) (very low- and low-density lipoprotein) concentrations were significantly lower in the hamsters fed the RPO (-42% and -48%), RBD-PO (-32% and -36%) and the reconstituted RBD-PO (-37% and -41%) compared to the coconut oil-fed hamsters. Plasma HDL-C concentrations were significantly higher by 14% and 31% in hamsters fed the RBD-PO and RPO compared to the coconut oil-fed hamsters. Plasma triglyceride (TG) concentrations were significantly lower in hamsters fed RBD-PO (-32%) and the reconstituted RBD-PO (-31%) compared to the coconut oil-fed hamsters. The plasma gamma-tocopherol concentrations were higher in the coconut oil-fed hamsters compared to the hamsters fed the RPO (60%), RBD-PO (42%) and the reconstituted RBD-PO (49%), while for plasma alpha-tocopherol concentrations, the coconut oil-fed hamsters were significantly higher than only the RPO-fed hamsters (21%). The coconut oil-fed hamsters also had significantly higher plasma lipid hydroperoxide concentrations compared to RBD-PO (112%) and the reconstituted RBD-PO (485%). The hamsters fed the coconut oil diet excreted significantly more fecal total neutral sterols and cholesterol compared to the hamsters fed the RBD-PO (158% and 167%, respectively). The coconut oil-fed hamsters had significantly higher levels of aortic total, free and esterified cholesterol compared to the hamsters fed the RPO (74%, 50% and 225%, respectively), RBD-PO (57%, 48% and 92%, respectively) and the reconstituted RBD-PO (111%, 94% and 94%, respectively). Also, aortic free/ester cholesterol ratio in the aortas of hamsters fed RPO was significantly higher than in those fed the coconut oil (124%). In conclusion, hamsters fed the three palm oil preparations had lower plasma TC and non-HDL-C and higher HDL-C concentrations while accumulating less aortic cholesterol concentrations compared to hamsters fed coconut oil.     

Effect of long term feeding of rice bran oil upon lipids and lipoproteins in rats

The effects of feeding two levels of rice bran oil (RBO) on the growth, lipid parameters, and fatty acid composition of the plasma and liver of rats (Wistar strain) were compared with those produced on animals which had been fed the same levels of peanut oil (PNO). The control animals were fed synthetic diets containing 5 and 20% peanut oil (PNO) and the experimental groups were fed similar diets, containing the same level of rice bran oil (RBO). There was no significant difference with respect to the organ weights between the control and the experimental groups. In general, groups fed 20% oil gained more weight than groups fed 5% oil. The animals which received rice bran oil in their diet had, in general, comparatively lower levels of cholesterol, triglycerides and phospholipids. On the other hand, animals receiving 20% rice bran oil in their diet, showed an increase of 20% in high density lipoproteins (HDL-C), within 18 weeks (p<0.05), when compared to the animals fed with peanut oil. Similarly, low density lipoprotein cholesterol (LDL-C) and very low density lipoprotein cholesterol (VLDL-C) were lower in RBO-fed groups, than in the PNO-fed groups. There was, however, no significant differences in the cholesterol/phospholipid (C/P) ratio of the two groups. Analysis of plasma and of liver fatty acids indicated, in a general way, the type of fat consumed. There were no significant difference in the P/S ratio, nor any in the oleic/linoleic, oleic/stearic, palmitoleic/palmitic, oleic/palmitic, and oleic/palmitoleic ratios. Furthermore, levels of saturated (SAFA), monounsaturated (MUFA), and polyunsaturated (PUFA) fatty acids were identical in both the groups. Thus, our results suggest that feeding a high level of rice bran oil (RBO) has no deleterious effect on the growth and blood lipid profile of rats.Abbreviations PNO peanut oil - RBO rice bran oil - HDL-C high density lipoprotein cholesterol - LDL-C low density lipoprotein cholesterol - VLDL-C very low density lipoprotein cholesterol - SAFA saturated fatty acids - MUFA mono-unsaturated fatty acids     

Corn fiber oil lowers plasma cholesterol levels and increases cholesterol excretion greater than corn oil and similar to diets containing soy sterols and soy stanols in hamsters

The aims of this study were to compare the cholesterol-lowering properties of corn fiber oil (CFO) to corn oil (CO), whether the addition of soy stanols or soy sterols to CO at similar levels in CFO would increase CO's cholesterol-lowering properties, and the mechanism(s) of action of these dietary ingredients. Fifty male Golden Syrian hamsters were divided into 5 groups of 10 hamsters each, based on similar plasma total cholesterol (TC) levels. The first group of hamsters was fed a chow-based hypercholesterolemic diet containing either 5% coconut oil + 0.24% cholesterol (coconut oil), 5% CO, 5% CFO, 5% CO + 0.6% soy sterols (sterol), or 5% CO + 0.6% soy stanols (stanol) in place of the coconut oil for 4 weeks. The stanol diet significantly inhibited the elevation of plasma TC compared to all other dietary treatments. Also, the CFO and sterol diets significantly inhibited the elevation of plasma TC compared to the CO and coconut oil diets. The CFO, sterol, and stanol diets significantly inhibited the elevation of plasma non-high density lipoprotein cholesterol compared to the CO and coconut oil diets. The stanol diet significantly inhibited the elevation of plasma high density lipoprotein cholesterol (HDL-C) compared to all other dietary treatments. The sterol diet significantly inhibited the elevation of plasma HDL-C compared to the CO and coconut oil diets, whereas the CFO diet significantly inhibited the elevation of plasma HDL-C compared to the coconut oil diet only. No differences were observed between the CFO and CO for plasma HDL-C. There were no differences observed between groups for plasma triglycerides. The CO and CFO diets had significantly less hepatic TC compared to the coconut oil, sterol, and stanol diets. The CO and CFO diets had significantly less hepatic free cholesterol compared to the sterol and stanol diets but not compared to the coconut oil diet; whereas the coconut oil and sterol diets had significantly less hepatic free cholesterol compared to the stanol diet. The CFO, sterol, and stanol diets excreted significantly more fecal cholesterol compared to the coconut oil and CO diets. In summary, CFO reduces plasma and hepatic cholesterol concentrations and increases fecal cholesterol excretion greater than CO through some other mechanism(s) in addition to increase dietary sterols and stanols-possibly oryzanols.     

Phytosterols and lecithin do not have an additive effect in lowering plasma and hepatic cholesterol levels in diet-induced hypercholesterolemic rats

Both plant sterols and lecithin are used as dietary supplements for lowering blood cholesterol in Western countries. This study evaluated the possibility of an additive effect of these ingredients on the regulation of lipid concentrations and cholesterol metabolism. Male Sprague-Dawley rats were randomly divided into three groups, and fed one of the following diets for 5 weeks; high cholesterol diet (HCD), phytosterol mixture-supplemented diet (PD, HCD+0.25% phytosterols), or phytosterol mixture and lecithin-supplemented diet (PLD, PD+0.15% lecithin). Feeding the PD for 5 weeks resulted in a 34% and 41% decrease in plasma total- and VLDL+LDL-cholesterol levels, respectively, and a 23% decrease in hepatic cholesterol content compared to those for the HCD rats (p < 0.05). These cholesterol-lowering properties of the phytosterol mixture were also associated with the down-regulation of hepatic acyl CoA:cholesterol acytransferase (ACAT) activity (p < 0.05). Addition of lecithin plus phytosterol mixture to the hypercholesterolemic diet did not significantly affect blood and hepatic lipid concentrations (with the exception of 36% decrease in hepatic triglyceride level, p < 0.05) as well as hepatic ACAT activity compared to feeding the hypercholesterolemic diet supplemented with phytosterol alone. These results indicate that combining lecithin, at a 0.15% level, with a phytosterol mixture-supplemented diet does not exhibit an additive effect in regulating hepatic ACAT activity or lowering blood cholesterol in hypercholesterolemic rats.     

Reduction of cholesterol absorption by dietary oleinate and fish oil in African green monkeys.

To determine whether diets enriched in monounsaturated or n-3 fatty acids cause a reduction in cholesterol absorption relative to those more enriched in saturated fatty acids, we measured cholesterol absorption in 18 African green monkeys fed diets enriched in lard, oleinate (oleic acid-rich safflower oil), or fish oil at two levels of dietary cholesterol (0.05 vs. 0.77 mg/kcal). All animals were initially challenged with the lard, high cholesterol diet to ascertain their responsiveness to dietary cholesterol. Based on the results of this challenge, low versus high responders were equally distributed in assignation to the low (n = 6) and high (n = 12) cholesterol regimens. Within each level of dietary cholesterol animals consumed all three dietary fats in random sequences during three experimental phases each lasting 9-12 months with a monkey chow washout period between each phase, so that each animal served as its own control. During each dietary phase measurements of plasma lipids and cholesterol absorption were performed. The animals fed the higher versus lower level of dietary cholesterol had significantly higher plasma total cholesterol and low density lipoprotein (LDL) cholesterol concentrations and lower percentage cholesterol absorption; high density lipoprotein (HDL) cholesterol levels were not affected by the level of dietary cholesterol. Dietary fish oil resulted in a 20-30% reduction (P less than 0.01) in total plasma and LDL cholesterol and a 30-40% reduction (P less than 0.01) in HDL cholesterol concentrations compared to lard and oleinate regardless of the level of dietary cholesterol. At the high level of cholesterol intake, the oleinate and fish oil diets resulted in significantly lower percentage cholesterol absorption compared to the lard fat diet (35 +/- 2%, 34 +/- 3%, 41 +/- 4%, respectively). At the lower level of dietary cholesterol, percentage cholesterol absorption values were higher than those at the high cholesterol intake (45-52% vs. 34-41%) but were not affected by the type of dietary fat. There was a significant positive correlation between plasma LDL cholesterol concentrations and percentage cholesterol absorption for the oleinate and lard diets at the high level of dietary cholesterol and a significant inverse association between plasma HDL cholesterol and percentage cholesterol absorption. We conclude that the type of dietary fat can influence cholesterol absorption in African green monkeys and that oleinate and fish oil reduce cholesterol absorption relative to lard when a high amount of cholesterol (0.77 mg/kcal) is present in the diet.     

Effects of increased dietary cholesterol with carbohydrate restriction on hepatic lipid metabolism in Guinea pigs

Excessive lipid accumulation within hepatocytes, or hepatic steatosis, is the pathognominic feature of nonalcoholic fatty liver disease (NAFLD), a disease associated with insulin resistance and obesity. Low-carbohydrate diets (LCD) improve these conditions and were implemented in this study to potentially attenuate hepatic steatosis in hypercholesterolemic guinea pigs. Male guinea pigs (n = 10 per group) were randomly assigned to consume high cholesterol (0.25 g/100 g) in either a LCD or a high-carbohydrate diet (HCD) for 12 wk. As compared with HCD, plasma LDL cholesterol was lower and plasma triglycerides were higher in animals fed the LCD diet, with no differences in plasma free fatty acids or glucose. The most prominent finding was a 40% increase in liver weight in guinea pigs fed the LCD diet despite no differences in hepatic cholesterol or triglycerides between the LCD and the HCD groups. Regardless of diet, all livers had severe hepatic steatosis on histologic examination. Regression analysis suggested that liver weight was independent of body weight and liver mass was independent of hepatic lipid content. LCD livers had more proliferating hepatocytes than did HCD livers, suggesting that in the context of cholesterol-induced hepatic steatosis, dietary carbohydrate restriction enhances liver cell proliferation.     

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.     

Dietary trans-18:1 raises plasma triglycerides and VLDL cholesterol when replacing either 16:0 or 18:0 in gerbils

To compare the relative impact of trans-18:1 with the two main dietary saturated fatty acids it replaces, plasma lipid response was assessed in Mongolian gerbils fed diets rich in 16:0 (24%en),18:0 (10%en), or trans-18:1 (4 or 6%en). The diets were designed such that the 18:0-rich diet substituted 7%en as 18:0 for 16:0, whereas 4%en and 6%en from trans-18:1 was substituted for 16:0 in the two trans diets. The control group was fed a diet formulated according to the fatty acid balance of American Heart Association (AHA), but provided 40%en as fat. Gerbils (n = 10 per dietary group) were fed one of the five diets for 8 weeks. The control diet, with 4 times the polyunsaturated fatty acids (PUFA) content and a P:S ratio about 10 times greater than the test diets, resulted in the lowest plasma TC, LDL cholesterol (LDL-C) and VLDL cholesterol (VLDL-C). Among the test diets, plasma TC and TG were lowest with the 18:0-rich diet. TC in gerbils fed the 16:0-rich diet and 4%en-trans were 20% higher than the 18:0-rich diet, while the 6%en-trans diet was 35% higher. VLDL-C was significantly higher in the 6%en-trans diet compared to all other groups at 8 weeks. Both trans fatty acid diets elevated plasma TG approximately 2- and 3-fold, respectively, compared to the 16:0-rich and 18:0-rich diets at 8 weeks. Further, plasma TG continued to rise over time with trans fatty acids compared to 16:0 or 18:0. Thus, in the fatty acid-sensitive gerbil, impaired TG metabolism represents a major aspect of the hyperlipemia caused by trans fatty acid substitution for major saturated fatty acids.     

Corn fiber oil and sitostanol decrease cholesterol absorption independently of intestinal sterol transporters in hamsters

OBJECTIVE: The aim of this study was to investigate the cholesterol-lowering mechanisms of corn fiber oil (CFO), ferulate phytostanyl esters (FPEs) and parent compounds of FPE, including sitostanol and ferulic acid, in hamsters. METHOD: Seventy male Golden Syrian hamsters were randomly assigned to six experimental diets for 4 weeks: (1) cornstarch-casein-sucrose-based control diet (control); and (2) control diet plus 0.1% (wt/wt) cholesterol (cholesterol-control). The remaining four groups were given cholesterol-control diet with: (3) 10% (wt/wt) CFO; (4) 0.5% (wt/wt) sitostanol; (5) 0.23% (wt/wt) ferulic acid; and (6) 0.73% (wt/wt) FPE. At the end of dietary intervention, total plasma cholesterol, high-density lipoprotein cholesterol and triglyceride concentrations were determined. Parameters of cholesterol kinetics, including cholesterol absorption and synthesis, as well as mRNA expression of sterol transporters such as Niemann-Pick C1 like 1 (NPC1L1), ATP-binding cassette G5 (ABCG5) and ABCG8, were assessed. RESULTS: Supplementation with CFO decreased (P<.0001) plasma total cholesterol levels by 29% as compared with the cholesterol-control group, while FPE and sitostanol reduced (P<.02) cholesterolemia by 15% and 14%, respectively. CFO and sitostanol decreased (P<.05) cholesterol absorption by 24% compared to the cholesterol-control group. Dietary intervention did not alter the intestinal gene expression of ABCG5, ABCG8 and NPC1L1. CONCLUSION: The present results show that the CFO-induced and sitostanol-induced decrease in cholesterol absorption is independent of intestinal enterocyte sterol transporters such as ABCG5, ABCG8 and NPC1L1 in hamsters.     

Decreased aortic early atherosclerosis and associated risk factors in hypercholesterolemic hamsters fed a high- or mid-oleic acid oil compared to a high-linoleic acid oil

Currently, diets higher in polyunsaturated fat are believed to lower blood cholesterol concentrations, and thus reduce atherosclerosis, greater than diets containing high amounts of saturated or possibly even monounsaturated fat. The present study was designed to investigate the effect of diets containing mid- or high-linoleic oil versus the typical high-linoleic sunflower oil on LDL oxidation and the development of early atherosclerosis in a hypercholesterolemic hamster model. Animals were fed a hypercholesterolemic diet containing 10% mid-oleic sunflower oil, high-oleic olive oil, or high-linoleic sunflower oil (wt/wt) plus 0.4% cholesterol (wt/wt) for 10 weeks. After 10 weeks of dietary treatment, only the animals fed the mid-oleic sunflower oil had significant reductions in plasma LDL-C levels (-17%) compared to the high-linoleic sunflower oil group. The high-oleic olive oil-fed hamsters had significantly higher plasma triglyceride levels (+41%) compared to the high-linoleic sunflower oil-fed hamsters. The tocopherol levels in plasma LDL were significantly higher in hamsters fed the mid-oleic sunflower oil (+77%) compared to hamsters fed either the high-linoleic sunflower or high-oleic olive oil. Measurements of LDL oxidation parameters, indicated that hamsters fed the mid-oleic sunflower oil and high-oleic olive oil diets had significantly longer lag phase (+66% and +145%, respectively) and significantly lower propagation rates (-26% and -44%, respectively) and conjugated dienes formed (-17% and -25%, respectively) compared to the hamsters fed the high-linoleic sunflower oil. Relative to the high-linoleic sunflower oil, aortic cholesterol ester was reduced by -14% and -34% in the mid-oleic sunflower oil and high-oleic olive oil groups, respectively, with the latter reaching statistical significance. Although there were no significant associations between plasma lipids and lipoprotein cholesterol with aortic total cholesterol and cholesterol esters for any of the groups, the lag phase of conjugated diene formation was inversely associated with both aortic total and esterified cholesterol in the high-oleic olive oil-fed hamsters (r = -0.69, P < 0.05). The present study suggests that mid-oleic sunflower oil reduces risk factors such as lipoprotein cholesterol and oxidative stress associated with early atherosclerosis greater than the typical high-linoleic sunflower oil in hypercholesterolemic hamsters. The high-oleic olive oil not only significantly reduced oxidative stress but also reduced aortic cholesterol ester, a hallmark of early aortic atherosclerosis greater than the typical high-linoleic sunflower oil.     

Effects of dietary alpha linolenic acid on cholesterol metabolism in male and female hamsters of the LPN strain

N-3 polyunsaturated fatty acids and estrogens are recognized as protective factors of atherosclerosis, however their interactions on cholesterol metabolism remain unclear. Male and female hamsters were fed for 9 weeks diets containing 12.5% lipids and rich in either alpha-linolenic acid ("linseed" diet) or saturated fatty acids ("butter" diet). Hamsters fed the "linseed" diet exhibited lower plasma concentrations of cholesterol (-29%), total LDL (-35%) and HDL (-17%), glucose (-20%), insulin (-40%) and of the LDL-cholesterol/HDL-cholesterol ratio (-27%) than those fed the "butter" diet. In the liver, cholesterol content was 2.7-fold lower in response to the "linseed" diet, whereas the concentration of HDL receptor (SR-BI) and the activities of HMGCoA reductase and cholesterol 7alpha-hydroxylase were 30 to 50% higher than with the "butter" diet. By contrast, the LDL receptor concentration did not vary with the diet. Females exhibited higher concentration of LDL (+24%), lower concentration of plasma triglycerides (-34%), total VLDL (-46%) and VLDL-cholesterol (-37%) and of biliary phospholipids (-19%). Besides, there was also an interaction between gender and diet: in males fed the "butter" diet, plasma triglycerides and VLDL concentration, were 2 to 4 fold higher than in the other groups. These data suggest that gene and/or metabolic regulations by fatty acids could interact with that of sex hormones and explain why males are more sensitive to dietary fatty acids.     

Effects of dietary cholesterol and hypothyroidism on rat apolipoprotein mRNA metabolism

The effects of dietary cholesterol and hypothyroidism on the mRNA levels of rat apolipoproteins A-I, A-IV, and E were measured in extracts of rat liver and rat intestine by hybridization to specific cDNA. Four groups, each comprised of six rats, were fed diets consisting of normal laboratory rat chow and either no supplements (control); 5% lard, 1% cholesterol, and 0.3% taurocholic acid (CF); 5% lard, 1% cholesterol, 0.3% taurocholic acid, and 0.1% propylthiouracil (CF-PTU); or 0.1% propylthiouracil (PTU) for 32 days. At the conclusion of the diets, serum cholesterol, triiodothyronine, and thyroxine levels were measured. The average serum cholesterol concentrations for the four groups were 50.4 +/- 3.7, 75.6 +/- 15.3, 135.3 +/- 41.5, and 73.3 +/- 16.4 mg/dl, respectively. The presence of propylthiouracil in the diets significantly lowered triiodothyronine and thyroxine levels in the serum. The mRNA levels for apolipoproteins A-I and A-IV in rat liver decreased significantly after the feeding of the CF-PTU diet (31 +/- 4% and 32 +/- 3% of normal, respectively) and the PTU diet (34 +/- 8% and 43 +/- 12% of normal, respectively), but showed little change after the CF diet (88 +/- 16% and 108 +/- 15% of normal, respectively). The effects of dietary propylthiouracil on the hepatic mRNA levels for apolipoproteins A-I and A-IV imply a role for thyroid hormones in regulating the mRNA levels for these apolipoproteins in rat liver. ApoE mRNA levels in the rat liver decreased slightly after the CF-PTU diet (74 +/- 12% of normal) and after the PTU diet (73 +/- 10% of normal).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects on plasma lipoproteins of monounsaturated, saturated, and polyunsaturated fatty acids in the diet of African green monkeys

Work by other investigators has shown that an increase in dietary content of monounsaturated fatty acids can result in a decreased plasma low density lipoprotein (LDL) cholesterol concentration. This observation, combined with the epidemiologic evidence that monounsaturated fat-rich diets are associated with decreased rates of death from coronary heart disease, suggests that inclusion of increased amounts of mono-unsaturated fat in the diet may be beneficial. The present study was carried out in a primate model, the African green monkey, to evaluate the effects of dietary monounsaturated fat on plasma lipoprotein cholesterol endpoints. Two study periods were carried out in which the fatty acid compositions of the experimental diets were varied. All diets contained 35% of calories as fat. In the first experimental period, a mixture of fats was used to set the dietary fatty acid composition to be approximately 50-60% of the desired fatty acid, either saturated, monounsaturated, or polyunsaturated (n-6). In the second experimental period, pure fats were used (palm oil, oleic acid-rich safflower oil, and linoleic acid-rich safflower oil) to maximize the difference in fatty acid composition. The effects of the more exaggerated dietary fatty acid differences of period 2 were similar to those that have been reported in humans. For the group fed the diet enriched in monounsaturated fat compared to saturated fat, whole plasma and LDL cholesterol concentrations were significantly lower while high density lipoprotein (HDL) cholesterol concentrations were not affected. For the group fed the diet enriched in polyunsaturated fat compared to saturated fat, both LDL and HDL cholesterol concentrations were significantly lower than in the group fed saturated fat. LDL cholesterol concentrations were comparable in the monounsaturated and polyunsaturated fat groups and the percentage of cholesterol in LDL was lowest in the monounsaturated fat fed group. Trends were similar for the mixed fat diets, although no statistically significant differences in plasma lipoprotein endpoints could be attributed to monounsaturated fatty acids in this dietary comparison. Since effects on plasma lipoproteins similar to those seen in humans were identified in this primate model, relevant mechanisms for the effects of dietary fatty acids on lipoprotein endpoints related to coronary artery atherosclerosis, per se, can subsequently be examined.     

Feeding unsaponifiable compounds from rice bran oil does not alter hepatic mRNA abundance for cholesterol metabolism-related proteins in hypercholesterolemic rats

The hypocholesterolemic effect of rice bran oil (RBO) is defined in human and animal experiments which indicate the presence of active component(s) in the unsaponifiable fraction, but the detailed mechanism is not known yet. Exogenously hypercholesterolemic (ExHC) rats were fed for 2 weeks on a 0.5% cholesterol diet supplemented with 10% each of RBO, RBO-simulated oil (RBOSO) in its fatty acid composition, or RBOSO plus 0.25% unsaponifiable compounds (UC) from RBO. Rats fed RBO or the UC resulted in lowing serum and liver cholesterol concentration and preventing reduction of high density lipoproteinic-cholesterol. Dietary RBO or the UC led to an elevation of fecal neutral sterol excretion, but no significant change in fecal bile acid excretion or in hepatic abundance of mRNAs for 3-hydroxy-3-methylglutaryl-CoA reductase, cholesterol-7alpha-hydroxylase, and low density lipoprotein receptor. Besides, serum and liver alpha-tocopherol concentrations were lowered in RBO or the UC-fed rats. These results show that the UC in RBO leads to a decreased serum cholesterol concentration by interrupting the absorption of intestinal hydrophobic compounds rather than by modifying cholesterol metabolism in the liver.     

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.     

Effects of dietary oyster extract on lipid metabolism, blood pressure, and blood glucose in SD rats, hypertensive rats, and diabetic rats

Oyster extract was prepared by hydrolysis of oyster protein with proteases, Aloase (a protease from Bacillus subtilis), and Pancitase (a protease from Aspergillus oryzae). Rats were fed a diet containing 20% casein (the control diet) or 15% casein and 5% oyster extract (the oyster extract diet) as the protein source. The oyster extract diet exerted a significant reduction in serum cholesterol and liver triglyceride concentrations as compared with the control diet in Sprague-Dawley (SD) rats fed cholesterol-supplemented diets for 4 weeks. The activities of cytosolic fatty acid synthase and glucose-6-phosphate dehydrogenase were significantly lower in the oyster extract group than in the control group in the liver of SD rats. Hepatic cholesterol and triglyceride concentrations were significantly lower in spontaneously hypertensive (SH) rats and Otsuka Long-Evans Tokushima Fatty (OLETF) rats, type 2 diabetic rats, fed the oyster extract diet, for 4 weeks and 4 months respectively, than in those fed the control diet in the cholesterol-free diet. Blood pressure was significantly lower in the oyster extract group than in the control group at the 2nd and 4th weeks after the beginning of feeding experimental diets in SH rats. These results suggest that oyster extract prepared by hydrolysis of oyster induces triglyceride-lowering activity in the liver through a decrease in hepatic lipogenesis in SD rats, and that it exerts the antihypertensive effect in SH rats.     

Soyasaponins lowered plasma cholesterol and increased fecal bile acids in female golden Syrian hamsters

A study was conducted in hamsters to determine if group B soyasaponins improve plasma cholesterol status by increasing the excretion of fecal bile acids and neutral sterols, to identify group B soyasaponin metabolites, and to investigate the relationship between a fecal group B soyasaponin metabolite and plasma lipids. Twenty female golden Syrian hamsters, 11-12 weeks old and 85-125 g, were randomly assigned to a control diet or a similar diet containing group B soyasaponins (containing no isoflavones), 2.2 mmol/kg, for 4 weeks. Hamsters fed group B soyasaponins had significantly lower plasma total cholesterol (by 20%), non-high-density lipoprotein (HDL) cholesterol (by 33%), and triglycerides (by 18%) compared with those fed casein (P < 0.05). The ratio of total cholesterol to HDL cholesterol was significantly lower (by 13%) in hamsters fed group B soyasaponins than in those fed casein (P < 0.05). The excretion of fecal bile acids and neutral sterols was significantly greater (by 105% and 85%, respectively) in soyasaponin-fed hamsters compared with those fed casein (P < 0.05). Compared with casein, group B soyasaponins lowered plasma total cholesterol levels and non-HDL cholesterol levels by a mechanism involving greater excretion of fecal bile acids and neutral sterols. Hamsters fed group B soyasaponins statistically clustered into two fecal soyasaponin metabolite-excretion phenotypes: high excreters (n = 3) and low excreters (n = 7). When high and low producers of this soyasaponin metabolite were compared for plasma cholesterol status, the high producers showed a significantly lower total-cholesterol-to-HDL-cholesterol ratio compared with the low producers (1.38 +/- 0.7 vs. 1.59 +/- 0.13; P < 0.03). Greater production of group B soyasaponin metabolite in hamsters was associated with better plasma cholesterol status, suggesting that gut microbial variation in soyasaponin metabolism may influence the health effects of group B soyasaponins.     

Effect of dietary chitosans with different viscosity on plasma lipids and lipid peroxidation in rats fed on a diet enriched with cholesterol

To investigate the effect of dietary chitosan on lipid metabolism, male SD (Sprague-Dawley) rats were fed a cholesterol-enriched diet containing 5% cellulose (CE), 5% chitosan (CCS; high viscosity), or 5% chitosan (FCS; low viscosity) for 4 weeks. The two types of chitosan with a comparable degree of deacetylation had a different molecular weight and intrinsic viscosity. Significantly (p < 0.05) lower plasma total cholesterol, LDL-cholesterol and VLDL-cholesterol concentrations were observed in the rats fed on the chitosan diets. In addition, chitosan significantly increased the fecal cholesterol and triglyceride contents. Although no significant difference in body weight was found among the dietary groups, the rats fed on the chitosan diets had lower relative liver weight when compared with those fed on the cellulose diet. Both of the chitosan groups had significantly lower liver total lipid and total cholesterol contents compared to the cellulose group, although the FCS group was less effective. The plasma and liver thiobarbituric acid reactive substances (TBAR) values were similar in the CE and FCS groups, while the CCS group had increased liver TBAR values. Although a significant increase in liver glucose-6-phosphate dehydrogenase activity was observed in the CCS group, no significant change was found in the FCS group. The observed influence of chitosans with different viscosity on the plasma lipid level, liver lipids and lipid peroxidation suggests that, while the hypocholesterolemic action of chitosans with different viscosity was similar, changes in the liver lipids and liver peroxidation status depended on their molecular weight when the deacetylation degree was comparable.     

Dietary methionine effects on plasma homocysteine and HDL metabolism in mice

The effects of dietary manipulation of folate and methionine on plasma homocysteine (Hcy) and high-density lipoprotein cholesterol (HDL-C) levels in wild-type and apolipoprotein-E-deficient mice were determined. A low-folate diet with or without folate and/or methionine supplementation in drinking water was administered for 7 weeks. Fasted Hcy rose to 23 microM on a low-folate/high-methionine diet, but high folate ameliorated the effect of high methionine on fasted plasma Hcy to approximately 10 microM. Determination of nonfasted plasma Hcy levels at 6-h intervals revealed a large diurnal variation in Hcy consistent with a nocturnal lifestyle. The daily average of nonfasted Hcy levels was higher than fasted values for high-methionine diets but lower than fasted values for low-methionine diets. An acute methionine load by gavage of fasted mice increased plasma Hcy 2.5 h later, but mice that had been on high-methionine diets had a lower fold induction. Mice fed high-methionine diets weighed less than mice fed low-methionine diets. Based on these results, two solid-food diets were developed: one containing 2% added methionine and the other containing 2% added glycine. The methionine diet led to fasted plasma Hcy levels of >60 microM, higher than those with methionine supplementation in drinking water. Mice on methionine diets had >20% decreased body weights and decreased HDL-C levels. An HDL turnover study demonstrated that the HDL-C production rate was significantly reduced in mice fed the methionine diet.