Hawthorn fruit is hypolipidemic in rabbits fed a high cholesterol diet.

The present study examined the hypolipidemic activity of hawthorn fruit. New Zealand white rabbits were fed one of three diets, a reference diet with no cholesterol added (NC), a high cholesterol diet (1 g/100 g, HC) and a HC diet supplemented with 2 g/100 g hawthorn fruit powder (HC-H). After 12 wk, serum total cholesterol (TC) and triacylglycerols (TG) were 23.4 and 22.2% lower, respectively, in the hawthorn fruit group compared with the HC rabbits (P < 0.05). Hawthorn supplementation led to 50.6% less cholesterol accumulation in aorta (P < 0.05) and 23-95% greater excretion of neutral and acidic sterols (P < 0.05). Supplementation of hawthorn fruit did not affect the activities of hepatic 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMG-CoA-R) or cholesterol 7alpha-hydroxylase (CH) but it suppressed the activity of intestinal acyl CoA:cholesterol acyltransferase (ACAT, P < 0.05). The results suggest that the mechanism by which hawthorn fruit decreases serum cholesterol involves, at least in part, the inhibition of cholesterol absorption mediated by down-regulation of intestinal ACAT activity.     

Carbohydrate restriction alters hepatic cholesterol metabolism in guinea pigs fed a hypercholesterolemic diet

The current study was undertaken to evaluate the effect of carbohydrate restriction on hepatic cholesterol metabolism in guinea pigs fed a hypercholesterolemic diet. Hartley male guinea pigs (n = 10 per group) were fed 1 of 3 diets: a diet with a percent energy distribution of 42:23:35 carbohydrate:protein:fat and 0.04% cholesterol (control), a diet with the same macronutrient distribution but with 0.25% cholesterol (HChol), or a carbohydrate-restricted (CR) diet with a percent energy distribution of 11:30:59 carbohydrate:protein:fat and 0.25% cholesterol for 12 wk. There was more accumulation of hepatic cholesterol and triglycerides as well as lower 3-hydroxy-3-methyl glutaryl-CoA reductase messenger RNA abundance in guinea pigs fed the high-cholesterol diets (HChol and CR) (P < 0.01). Guinea pigs fed the CR diet had lower concentrations of hepatic total cholesterol and cholesteryl ester than those fed the HChol diet (P < 0.05). There was no diet effect on hepatic LDL receptor expression. Hepatic acyl CoA cholesteryl acyltransferase (ACAT) activity was lowest in guinea pigs fed the low-cholesterol diet (9.7 +/- 4.8 pmol.min(-1).mg(-1)), intermediate in those fed the CR diet (37.3 +/- 12.4 pmol.min(-1).mg protein(-1)), and highest in guinea pigs fed the HChol diet (55.9 +/- 11.2 pmol.min(-1).mg(-1)). ACAT activity was significantly correlated with hepatic cholesterol (r = 0.715; P < 0.01) and LDL cholesterol (r = 0.59; P < 0.01) for all dietary groups, suggesting a major role of this enzyme in hepatic cholesterol homeostasis and in lipoprotein concentrations. These results indicate that dietary cholesterol increases hepatic lipid accumulation and affects hepatic cholesterol homeostasis. Carbohydrate restriction in the presence of high cholesterol is associated with lower hepatic ACAT activity and an attenuation of hepatic cholesterol accumulation.     

Grape polyphenols decrease plasma triglycerides and cholesterol accumulation in the aorta of ovariectomized guinea pigs

Female ovariectomized guinea pigs, a model for menopausal women, were fed either a control diet or a diet containing 10 g/100 g of a lyophilized grape preparation for 12 wk. The macronutrient composition of the grape preparation was: simple carbohydrates, 90 g/100 g; protein, 4 g/100 g; and dietary fiber, 6 g/100 g. Control and grape diets had the same composition except for the percentage of macronutrients provided by the grape preparation. Polyphenols were present in the grape preparation at 0.58 g/100 g and included flavans, anthocyanins, quercetin, myricetin, kaempferol and resveratrol. Dietary cholesterol was 0.33 g/100 g to raise plasma cholesterol concentrations and ensure the development of atherosclerosis. Plasma LDL cholesterol concentrations did not differ between groups, whereas plasma triglycerides and VLDL cholesterol were 39 and 50% lower, respectively in guinea pigs fed the grape diet compared with controls (P < 0.05). Significant modifications in LDL particles included 58 and 30% lower triglycerides and phospholipids, respectively (P < 0.0001). Hepatic acyl CoA:cholesteryl acyltransferase activity was 27% lower (P < 0.05) in the grape diet-fed group compared with controls. In addition, concentrations of cholesterol in the aorta were 33% lower (P < 0.05) in guinea pigs fed the grape diet. These results suggest that grape intake in ovariectomized guinea pigs alters hepatic cholesterol metabolism, which may affect VLDL secretion rates and result in less accumulation of cholesterol in the aorta.     

Dietary conjugated linoleic acid mixture affects the activity of intestinal acyl coenzyme A: cholesterol acyltransferase in hamsters

The present study was designed to study the mechanisms by which dietary conjugated linoleic acids (CLA) decrease serum cholesterol. Hamsters were fed a semi-synthetic diet containing 1 g cholesterol/kg diet with or without supplementation with 20 g linoleic acid (LA) and 20 g CLA/kg diet. After 8 weeks, serum fasting total cholesterol (TC) and triacylglycerol (TG) were significantly lower in the LA-supplemented and CLA-supplemented groups compared with those of the control (CTL) hamsters. In contrast to LA, CLA significantly lowered hepatic cholesterol but it increased the level of adipose tissue cholesterol, suggesting that the hypocholesterolaemic mechanism of CLA is different from that of LA. CLA decreased the activity of intestinal acyl CoA:cholesterol acyltransferase (ACAT) whereas LA had no effect on this enzyme. Consequently, CLA supplementation increased the faecal excretion of total neutral sterols, but it had no or little effect on the faecal acidic sterols. If the ACAT is associated with cholesterol absorption, the part of mechanisms by which CLA decreases serum cholesterol may involve down-regulation of intestinal ACAT activity.     

Plasma and hepatic cholesterol and hepatic activities of 3-hydroxy-3-methyl-glutaryl-CoA reductase and acyl CoA: cholesterol transferase are lower in rats fed citrus peel extract or a mixture of citrus bioflavonoids.

The cholesterol-lowering effects of tangerine peel extract and a mixture of two citrus flavonoids were tested. Male rats were fed a 1 g/100 g high-cholesterol diet for 42 d with supplements of either tangerine-peel extract or a mixture of naringin and hesperidin (0.5 g/100 g) to study the effects of plasma and hepatic lipids, hepatic enzyme activities, and the excretion of fecal neutral sterols. Both the tangerine-peel extract and mixture of two flavonoids significantly lowered the levels (mean +/- SE) of plasma (2.44 +/- 0. 59 and 2.42 +/- 0.31 mmol/L, vs. 3.80 +/- 0.28 mmol/L, P < 0.05), hepatic cholesterol (0.143 +/- 0.017 and 0.131 +/- 0.010 mmol/g vs. 0.181 +/- 0.003 mmol/g, P < 0.05), and hepatic triglycerides (0.069 +/- 0.007 and 0.075 +/- 0.006 mmol/g vs. 0.095 +/- 0.002 mmol/g, P < 0.05) compared to those of the control. The 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase (1565.0 +/- 106. 0 pmol. min-1. mg protein-1 and 1783.0 +/- 282 pmol. min-1. mg protein-1 vs. 2487.0 +/- 210.0 pmol. min-1. mg protein-1, P < 0.05) and acyl CoA: cholesterol O-acyltransferase (ACAT) activities (548.0 +/- 65.0 and 615.0 +/- 80.0 pmol. min-1. mg protein-1 vs. 806.0 +/- 105.0 pmol. min-1. mg protein-1, P < 0.05) were significantly lower in the experimental groups than in the control. These supplements also substantially reduced the excretion of fecal neutral sterols compared to the control (211.1 +/- 26.7 and 208.2 +/- 31.6 mg/d vs. 521.9 +/- 53.9 mg/d). The inhibition of HMG-CoA reductase and ACAT activities resulting from the supplementation of either tangerine-peel extract or a combination of its bioflavonoids could account for the decrease in fecal neutral sterol that appears to compensate for the decreased cholesterol biosynthesis in the liver.     

High protein buckwheat flour suppresses hypercholesterolemia in rats and gallstone formation in mice by hypercholesterolemic diet and body fat in rats because of its low protein digestibility

OBJECTIVE: This study evaluated the physiologic properties of high protein buckwheat flour (PBF) by examining its effects on serum cholesterol and body fat in rats and on cholesterol gallstone formation in mice. METHODS: Animals were fed experimental diets that contained casein, buckwheat protein extract (BWP), or PBF as a protein source (net protein content 200 g/kg). RESULTS: In experiment 1, consumption of PBF and BWP for 10 d caused 33% and 31% decreases, respectively, in serum cholesterol of rats fed cholesterol-enriched diets when compared with consumption of casein (P < 0.05). Dietary PBF caused a significant decrease in liver cholesterol, whereas dietary BWP caused only a slight decrease (P > 0.05). Fecal excretion of neutral and acidic steroids in the PBF group was significantly higher than those in the BWP and casein groups. In experiment 2, consumption of PBF for 10 d significantly suppressed adipose tissue weight and hepatic activity of fatty acid synthase in rats fed cholesterol-free diets compared with consumption of casein (P < 0.05), whereas that of BWP for this period caused only a slight decrease in adipose tissue weight (P > 0.05). In experiment 3, dietary PBF and BWP significantly decreased the incidence of cholesterol gallstones and lithogenic index in mice fed cholesterol-enriched diets for 27 d, which was associated with increased fecal excretion of acidic steroids. CONCLUSION: This study demonstrated that PBF has strong activities against hypercholesterolemia, obesity, and gallstone formation, suggesting a potential usefulness of PBF as functional ingredient.     

A rice bran oil diet increases LDL-receptor and HMG-CoA reductase mRNA expressions and insulin sensitivity in rats with streptozotocin/nicotinamide-induced type 2 diabetes

A rice bran oil (RBO) diet can reduce plasma lipids; this was attributed to the specific components, gamma-oryzanol and gamma-tocotrienol, which individually were shown to be hypocholesterolemic; however, the mechanism of their effects on diabetic hyperlipidemia and the development of diabetes is not known. Rats with streptozotocin/nicotinamide-induced type 2 diabetes were divided into control, RO10, and RO15 groups, and fed cholesterol-free diets containing 0, 10, and 15 g RBO with 0, 352, and 528 g gamma-oryzanol and 0, 6.0 and 9.0 mg gamma-tocotrienol/100 g diet for 4 wk. Diabetic rats fed the RBO diet had greater insulin sensitivity (P = 0.02) than rats fed the control diet. Diabetic rats fed the RBO diet also had lower plasma triglyceride (P = 0.003), LDL cholesterol (P = 0.028), and hepatic triglyceride concentrations (P = 0.04), as well as greater fecal neutral sterol and bile acid excretion than those fed the control diet. After 4 wk, there was an approximately 100% (P < 0.001) increase in the abundance of hepatic cholesterol 7alpha-hydroxylase, an 89% (P < 0.001) increase in the hepatic LDL-receptor, and a 50% (P < 0.001) increase in hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase mRNA in rats fed the RBO diet compared with those fed the control diet. These findings support the conclusion that a rice bran oil-containing diet can significantly suppress hyperlipidemic and hyperinsulinemic responses in diabetic rats. The high contents of gamma-oryzanol and gamma-tocotrienol in RBO can lead to increased fecal neutral sterol and bile acid excretion, via upregulation of cholesterol synthesis and catabolism.     

Aronia melanocarpa (chokeberry) polyphenol–rich extract improves antioxidant function and reduces total plasma cholesterol in apolipoprotein E knockout mice

We hypothesized that a polyphenol-rich chokeberry extract (CBE) would modulate hepatic lipid metabolism and improve antioxidant function in apolipoprotein E knockout (apoE^−/−) mice. ApoE^−/− mice were fed diets containing 15% fat with 0.2% cholesterol alone or supplemented with 0.005% or 0.05% CBE for 4 weeks. CBE polyphenol content was determined by the total phenols, 4-dimethylaminocinnamaldehyde, and ultra high-performance liquid chromatography-mass spectrometry methods. The 0.05% CBE diet provided mice with mean daily doses of 1.2 mg gallic acid equivalents of total phenols, 0.19 mg anthocyanins, 0.17 mg phenolic acids, 0.06 mg proanthocyanidins (as catechin-equivalents), and 0.02 mg flavonols. The 0.05% CBE group had 12% less plasma total cholesterol concentrations than the control. Despite the hypocholesterolemic effect of CBE, hepatic mRNA levels of low-density lipoprotein receptor, hydroxyl-3-methylglutaryl coenzyme A reductase and cholesterol 7α-hydroxylase in CBE-fed mice were not significantly different from controls. Dietary CBE did not alter hepatic lipid content or the hepatic expression of genes involved in lipogenesis and fatty acid β-oxidation such as fatty acid synthase, carnitine palmitoyltransferase 1 and acyl-CoA oxidase. Plasma paraoxonase and catalase activities were significantly increased in mice fed 0.05% CBE. Both CBE diets increased hepatic glutathione peroxidase (GPx) activity but the 0.05% CBE group had 24% less proximal intestine GPx activity relative to controls. Thus, dietary CBE lowered total cholesterol and improved plasma and hepatic antioxidant function at nutritionally-relevant doses in apoE^−/− mice. Furthermore, the CBE cholesterol-lowering mechanism in apoE^−/− mice was independent of hepatic expression of genes involved in cholesterol metabolism.     

Menhaden oil decreases high-fat diet-induced markers of hepatic damage, steatosis, inflammation, and fibrosis in obese Ldlr-/- mice

The frequency of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) has increased in parallel with obesity in the United States. NASH is progressive and characterized by hepatic damage, inflammation, fibrosis, and oxidative stress. Because C20-22 (n-3) PUFA are established regulators of lipid metabolism and inflammation, we tested the hypothesis that C20-22 (n-3) PUFA in menhaden oil (MO) prevent high-fat (HF) diet-induced fatty liver disease in mice. Wild-type (WT) and Ldlr(-/-) C57BL/6J mice were fed the following diets for 12 wk: nonpurified (NP), HF with lard (60% of energy from fat), HF-high-cholesterol with olive oil (HFHC-OO; 54.4% of energy from fat, 0.5% cholesterol), or HFHC-OO supplemented with MO (HFHC-MO). When compared with the NP diet, the HF and HFHC-OO diets induced hepatosteatosis and hepatic damage [elevated plasma alanine aminotransferase (ALT) and aspartate aminotransferases] and elevated hepatic expression of markers of inflammation (monocyte chemoattractant protein-1), fibrosis (procollagen 1α1), and oxidative stress (heme oxygenase-1) (P ≤ 0.05). Hepatic damage (i.e., ALT) correlated (r = 0.74, P < 0.05) with quantitatively higher (>140%, P < 0.05) hepatic cholesterol in Ldlr(-/-) mice fed the HFHC-OO diet than WT mice fed the HF or HFHC-OO diets. Plasma and hepatic markers of liver damage, steatosis, inflammation, and fibrosis, but not oxidative stress, were lower in WT and Ldlr(-/-) mice fed the HFHC-MO diet compared with the HFHC-OO diet (P < 0.05). In conclusion, MO [C20-22 (n-3) PUFA at 2% of energy] decreases many, but not all, HF diet-induced markers of fatty liver disease in mice.     

Dietary fat type and cholesterol quantity interact to affect cholesterol metabolism in guinea pigs.

Interactions of dietary fat saturation with dietary cholesterol on cholesterol homeostasis in guinea pigs were studied by feeding 15% (wt/wt) fat diets containing lard, olive oil or corn oil, with 0.00, 0.08, 0.17 or 0.33% added cholesterol. Plasma total and LDL cholesterol concentrations significantly increased with increasing dietary cholesterol, with pronounced increments occurring at the pharmacologic (0.33%) level. An interaction between fat type and dietary cholesterol was seen for HDL cholesterol concentrations. Saturated fat and the pharmacologic level of dietary cholesterol increased plasma HDL concentrations, whereas polyunsaturated fat minimized the dietary cholesterol-mediated increase. Interactions were also observed for hepatic cholesterol: dietary cholesterol increased both free and esterified hepatic cholesterol concentrations in all groups fed all the dietary fats, and fat type influenced the extent of hepatic cholesterol accumulation. Lard-fed animals accumulated the least hepatic cholesterol over the range of dietary cholesterol intakes. Dietary cholesterol suppressed hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity, with maximal suppression at all levels of cholesterol intake. Dietary cholesterol had a greater effect on plasma and hepatic cholesterol concentrations and hepatic HMG-CoA reductase activity than did fat type. The data indicated limited interactions of fat type and cholesterol quantity in altering mechanisms regulating plasma cholesterol homeostasis.     

The effect of dietary fat saturation on plasma and hepatic lipoproteins in the rat

Semipurified diets containing 10% kilocalories from either safflower oil (SO), corn oil (CO), olive oil (OO) or palm oil (PO) were fed to weanling male rats for 2 weeks. The effects of dietary fat saturation on plasma lipids and lipoproteins were: 1) Nonfasted plasma cholesterol concentration was higher in rats fed OO (mean +/- SEM = 81.0 +/- 2.9 mg/dl) vs. CO (67.5 +/- 2.9); 2) plasma chylomicron cholesterol concentration was higher in rats fed OO vs. SO and CO, with PO values in between; and 3) the cholesterol concentration of plasma very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL) did not differ among groups. The effects of dietary fat saturation on hepatic lipoproteins (determined by liver perfusion techniques) were: 1) hepatic higher density lipoprotein (d = 1.006-1.21 g/ml) cholesterol production was greater in rats fed SO and CO vs. PO [19.1 +/- 1.2, 17.2 +/- 0.8 and 13.7 +/- 1.6 micrograms/(g liver X 1.5 hour), respectively]; 2) there was no difference in hepatic VLDL cholesterol production among groups; and 3) the ratio of cholesterol to protein of hepatic VLDL and the higher density lipoprotein fraction was higher in rats fed diets rich in polyunsaturated fatty acids versus saturated fatty acids. Dietary fat saturation had no effect on carcass and liver cholesterol concentrations. Since differences in hepatic lipoprotein production were not reflected in plasma lipoprotein patterns, these results suggest that extrahepatic lipoprotein metabolism differs in rats fed diets containing fatty acids of varying saturation.     

Dietary taurine alters ascorbic acid metabolism in rats fed diets containing polychlorinated biphenyls

The effect of dietary taurine on ascorbic acid metabolism and hepatic drug-metabolizing enzymes was investigated in rats fed diets containing polychlorinated biphenyls (PCB) to determine whether taurine has an adaptive and protective function in xenobiotic-treated animals. Young male Wistar rats (60 g) were fed diets containing 0 or 0.2 g/kg diet PCB with or without 30 g/kg diet of taurine for 14 d. The rats fed the PCB-containing diets had greater liver weight, higher ascorbic acid concentrations in the liver and spleen and greater hepatic cytochrome P-450 contents than control rats that were not treated with PCB (P < 0.01). In PCB-fed rats, urinary ascorbic acid excretion was enhanced, and serum cholesterol concentration (especially HDL-cholesterol) was significantly elevated compared with those in control rats. Dietary taurine significantly potentiated the increases in the urinary excretion of ascorbic acid and the rise in the levels of cytochrome P-450 which were caused by PCB treatment. On the other hand, the supplementation of taurine to control diet did not alter these variables. Taurine may enhance the hepatic drug-metabolizing systems, leading to the stimulation of the ascorbic acid metabolism in rats fed diets containing PCB.     

Dietary fat saturation distinctly affects apolipoprotein gene expression and high density lipoprotein size distribution in two strains of Golden Syrian hamsters

Plasma lipoprotein levels, high density lipoprotein (HDL) particle size distribution and tissue mRNA levels for several apolipoproteins were determined in two strains of Golden Syrian hamsters characterized as high (F1B) or low (LVG) responders to atherogenic diets. Twenty-four male hamsters per strain were fed semipurified diets containing 0.2 g/100 g diet cholesterol and 15 g/100 g diet fat enriched (13 g/100 g) with either coconut oil or soybean oil for 18 weeks. HDL size was analyzed by non-denaturing gradient (4–30%) polyacrylamide gel electrophoresis, and categorized into four HDL subspecies according to Stoke’s diameter. Hepatic and intestinal mRNA apolipoprotein concentrations were measured using solution hybridization/ribonuclease protection assay. Compared to F1B hamsters, the LVG hamsters showed a less atherogenic lipoprotein profile; with lower triglycerides (P < 0.01) and higher HDL cholesterol (P < 0.01) levels. Consumption of a polyunsaturated fatty acid (PUFA) diet induced the decrease in triglyceride levels (42% in LVG, P < 0.05 and 51% in F1B, P < 0.01) and in HDL cholesterol (15% in LVG, P < 0.05 and 28% in F1B, P < 0.01). LVG animals had a greater proportion of larger HDL particles than F1B animals regardless of the diet (P < 0.01). Consumption of the soybean oil diet, compared with coconut oil diet, lowered the proportion of HDL2b and increased the proportion of HDL2a and HDL3 in LVG animals. However, F1B animals consuming the PUFA diet had a decrease in the percentage of HDL2b and HDL2a and a marked increase in HDL3. ApoA-I mRNA levels were higher in F1B animals (P < 0.01), and were not affected by dietary fat saturation in either strain of hamsters. ApoA-II mRNA levels were higher in the LVG strain (P < 0.001), and increased with fat saturation of both strains (P < 0.05). The average ratio of intestinal apoC-II/C-III mRNA was 3.2 times higher in LVG animals (P < 0.05) as compared with F1B animals. This is consistent with a higher lipolytic activity in LVG animals that will result in lower triglyceride concentrations and increased HDL particle size. Dietary induced effects on HDL particle size may be attributed to the higher levels of apoA-II mRNA as well as an increased neutral lipid exchange between HDL and triglyceride-rich lipoproteins due to the elevated triglyceride levels in animals fed on saturated diet.     

Corn fiber oil lowers plasma cholesterol by altering hepatic cholesterol metabolism and up-regulating LDL receptors in guinea pigs

To evaluate some of the mechanisms involved in the hypocholesterolemic effects of corn fiber oil (CFO), male Hartley guinea pigs were fed diets containing increasing doses of CFO [0 (control), 5, 10 or 15 g/100 g]. Total fat was adjusted to 15 g/100 g in all diets with regular corn oil. Diets contained 0.25 g/100 g cholesterol. A positive control group (LC) with low dietary cholesterol (0.04 g/100 g) was also included. Plasma LDL cholesterol concentrations were 32, 55 and 57% (P < 0.0005) lower with increasing doses of CFO. Compared with controls, intake of CFO resulted in 27-32% lower hepatic microsomal cholesterol (P < 0.0001), the regulatory pool of LDL receptor (LDL-R) expression. CFO intake resulted in favorable plasma and hepatic cholesterol concentrations, similar to those in guinea pigs fed the LC diet. Hepatic cholesterol 7alpha-hydroxylase (CYP7) activity was approximately 88% higher in guinea pigs fed the two higher dosages of CFO (P < 0.05). In parallel, CYP7 mRNA abundance was approximately 88% higher in guinea pigs fed all three CFO diets. CFO treatment also induced hepatic LDLR mRNA by 66-150% with significant differences at the highest CFO dose. These results suggest that CFO, as a result of decreased bile acid absorption, increased mRNA abundance and activity of CYP7. Because hepatic cholesterol is the substrate for CYP7, a lowering of cholesterol concentrations in the total and microsomal pools was observed. As a response to the depleted microsomal free cholesterol pool, the LDL receptor was up-regulated, drawing more cholesterol from plasma, thus leading to the observed decrease in plasma LDL cholesterol concentrations.     

Palm tocotrienols protect ApoE +/- mice from diet-induced atheroma formation

We evaluated the effects of vitamin E and beta-carotene on apolipoprotein (apo)E +/- female mice, which develop atherosclerosis only when fed diets high in triglyceride and cholesterol. Mice were fed a nonpurified control diet (5.3 g/100 g triglyceride, 0.2 g/100 g cholesterol), an atherogenic diet alone (15.8 g/100 g triglyceride, 1.25 g/100 g cholesterol, 0.5 g/100 g Na cholate) or the atherogenic diet supplemented with either 0.5 g/100 g (+)-alpha-tocopherol (mixed isomers); 0.5 g/100 g palm tocopherols (palm-E; 33% alpha-tocopherol, 16.1% alpha-tocotrienol, 2.3% beta-tocotrienol, 32.2% gamma-tocotrienol, 16.1% delta-tocotrienol); 1.5 g/100 g palm-E; or 0.01 g/100 g palm-carotenoids (58% beta-carotene, 33% alpha-carotene, 9% other carotenoids). Compared with mice fed the control diet, plasma cholesterol was fourfold greater in mice fed the atherogenic diet. Mice fed the 1.5 g/100 g palm-E supplement had 60% lower plasma cholesterol than groups fed the other atherogenic diets. Mice fed the atherogenic diet had markedly higher VLDL, intermediate density lipoprotein (IDL) and LDL cholesterol and markedly lower HDL cholesterol than the controls. Lipoprotein patterns in mice supplemented with alpha-tocopherol or palm carotenoids were similar to those of the mice fed the atherogenic diet alone, but the pattern in mice supplemented with 1. 5 g/100 g palm-E was similar to that of mice fed the control diet. In mice fed the atherogenic diet, the hepatic cholesterol plus cholesterol ester concentration was 4.4-fold greater than in mice fed the control diet. Supplementing with 1.5 g/100 g palm-E lowered hepatic cholesterol plus cholesterol ester concentration 66% compared with the atherogenic diet alone. Mice fed the atherogenic diet had large atherosclerotic lesions at the level of the aortic valve. With supplements of 0.5 g/100 g palm-E or 1.5 g/100 g palm-E, the size of the lesions was 92 or 98% smaller, respectively. The 0.5 g/100 g alpha-tocopherol and palm carotenoid supplements had no effect. Supplements did not alter mRNA abundance for apolipoproteins A1, E, and C3. The beneficial effect of tocotrienols on atherogenesis, the plasma lipoprotein profile and accumulation of hepatic cholesterol esters cannot be attributed to their antioxidant properties.     

Jasmine green tea epicatechins are hypolipidemic in hamsters (Mesocricetus auratus) fed a high fat diet.

These studies were designed to test the hypolipidemic activity of green tea epicatechins (GTE) isolated from jasmine green tea. In Experiment 1, three groups of hamsters were given a semisynthetic diet containing 200 g lard/kg and 1 g cholesterol/kg for 4 wk. The control group received distilled water, and the other two groups received either 15 g/L green tea water extract (GTWE) or 5.0 g/L GTE solution. Both the GTWE and GTE groups had lower concentrations of serum total cholesterol (TC) and triacylglycerols (TG) than the controls (P < 0.05). In Experiment 2, four groups of hamsters received tap water as the drinking fluid, but they were given the same high fat and cholesterol diet supplemented with 0 (control), 1.1, 3.4 or 5.7 g GTE/kg diet. The hypolipidemic effect of jasmine GTE was dose dependent. In Experiment 3, the time-course of changes in serum TC and TG was monitored in hamsters given the high fat diet supplemented with 5.7 g GTE/kg in comparison with that of controls. The hypolipidemic effects of dietary GTE were evident after feeding for 2 wk. Dietary supplementation of GTE did not affect liver fatty acid synthase. However, GTE-supplemented hamsters had higher fecal excretions of total fatty acids, neutral sterols and acidic sterols compared with the control group. In Experiment 4, hamsters were fed nonpurified diet; the control group drank distilled water, and the GTE group drank distilled water containing 5.0 g GTE/L. No differences in activities of 3-hydroxy-3-methyl glutaryl coenzyme A reductase and intestinal acyl CoA:cholesterol acyltransferase were observed. This study suggests that the hypolipidemic activity of GTE is not due to inhibition of synthesis of cholesterol or fatty acid but is most likely mediated by its influence on absorption of dietary fat and cholesterol.     

Regulation of cholesterol and lipoprotein metabolism in guinea pigs mediated by dietary fat quality and quantity.

The effects of dietary fat quality and quantity on regulation of cholesterol and lipoprotein metabolism were measured in guinea pigs. The animals were fed 7.5 or 15% (wt/wt) fat diets containing either polyunsaturated corn oil (CO), monounsaturated olive oil (OL) or saturated lard as the fat source. Dietary fat quality had a number of significant effects: animals fed the CO-based diet had lower plasma LDL levels and LDL particles of higher density with decreased ratios of core-to-surface components. Apoprotein B/E receptor-mediated binding of LDL to hepatic membranes was twofold higher for animals fed the CO-based diet. Animals fed the OL-based diet had lower hepatic 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase activity and increased levels of hepatic cholesterol. Hepatic cholesteryl ester levels were lowest for animals fed the lard-based diet. Increasing dietary fat quantity resulted in increased plasma LDL levels and hepatic cholesterol, HMG-CoA reductase activity and receptor affinity for LDL. No changes were observed in LDL binding. These data demonstrate that, independent of dietary fat quantity, CO-based diets lower plasma LDL levels, modify LDL composition and increase hepatic apoprotein B/E receptor number.     

Prickly pear (Opuntia sp.) pectin reverses low density lipoprotein receptor suppression induced by a hypercholesterolemic diet in guinea pigs.

The effects of prickly pear pectin on plasma LDL metabolism were investigated by feeding guinea pigs either a diet containing 15 g/100 g lard and 0.25 g/100 g cholesterol (LC diet) or the LC diet in which cellulose was partially replaced (2.5 g/100 g) by prickly pear pectin (LC-P diet). The LC-P diet lowered plasma LDL cholesterol concentrations by 33% (P < 0.001). Low density lipoprotein composition was modified by intake of prickly pear pectin; the relative percentages of free and esterified cholesterol were lower and triglycerides were higher in LDL from animals fed the LC-P diet (P < 0.05). Intake of prickly pear pectin did not affect hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase activity; however, hepatic free and esterified cholesterol concentrations were lowered by 46 and 64%, respectively. Hepatic apolipoprotein B/E receptor expression (Bmax) was 60% higher in animals fed the LC-P diet (P < 0.01). Similar to the in vitro data, receptor-mediated LDL fractional catabolic rates were 190% higher in animals fed the LC-P diet (P < 0.05), whereas apolipoprotein LDL flux rates were not affected. Apolipoprotein LDL pool size and fractional catabolic rates exhibited a significant correlation (r = -0.52, P < 0.01). These data indicate that an increase in apolipoprotein B/E receptor expression is a major metabolic response by which intake of prickly pear pectin decreases plasma LDL concentrations.