Effects of a mixture of organisms, Lactobacillus acidophilus or Streptococcus faecalis on cholesterol metabolism in rats fed on a fat- and cholesterol-enriched diet.The effect of a mixture of organisms (a probiotic mixture) comprising Bacillus, Lactobacillus, Streptococcus, Clostridium, Saccharomyces and Candida (10(7-8) colony-forming units/g rice bran of each component) on lipid metabolism was compared with that of L. acidophilus and that of S. faecalis. There were four treatment groups: rice bran (control), the mixture of organisms, L. acidophilus or S. faecalis (30 g/kg) were given to rats in a fat- and cholesterol-enriched diet for 4 weeks. The serum total cholesterol concentration of the group fed on the mixture of organisms was reduced by 15-33% compared with the other groups at the end of the 4-week feeding period (P < 0.05). This group also had a lower hepatic cholesterol concentration (36-44%) than the two single-bacteria groups (P < 0.05). 3-Hydroxy-3-methylglutaryl-Co A reductase (NADPH; EC 1.1.1.34) activities of the mixed-organism and L. acidophilus groups were significantly lower (61-63%) than those of the other groups (P < 0.05); the activity of the S. faecalis group was also significantly lower (42%) than that of the control group (P < 0.05). The faecal cholesterol and bile acid concentrations of the mixed-organism group increased compared with those of the L. acidophilus and S. faecalis groups (P < 0.05). The capacity of the mixed-organism cells to bind bile salt in vitro was significantly higher (approximately 50%) than that of the single-bacteria cells (P < 0.05). On the other hand, cholesterol micelle formation for the mixed-organism cells was significantly (approximately 9%) lower than that of the single-bacteria cells (P < 0.05). These results indicate that the mixture of organisms decreased the synthesis of cholesterol in the liver and increased the loss of steroids from the intestine, in rats. Thus, the mixture of organisms had a hypocholesterolaemic role.

An investigation of the relationship between estrogen, estrogen metabolites and blood cholesterol levels in ovariectomized rats.17 beta-Estradiol (E2) has long been known for protecting against Coronary Heart Disease by lowering cholesterol levels in premenopausal women. A recent study in our laboratory suggested that two hydroxylated metabolites of E2 possess similar hypocholesterolemic effects in male rats. This effect has been further investigated with additional estrogen metabolites in ovariectomized rats with a view toward mimicking the true postmenopausal situation in humans. Their effects in reproductive tissues were also evaluated histologically. Fundamentally, the following issues were addressed: (1) Do oxidized metabolites of estradiol lower total cholesterol levels? (2) Can a hypocholesterolemic effect be achieved without eliciting estrogenic activities on reproductive tissues? The results of this investigation showed that a number of oxygenated metabolites of estradiol can lower cholesterol levels. Among them, 4-hydroxyestradiol (4-OHE2) produced a striking hypocholesterolemic effect and a substantial uterotropic effect. 2-Hydroxyestradiol (2-OHE2), 2-methoxyestradiol (2-meoE2) and 2-methoxyestrone (2-meoE1) produced a significant decrease in cholesterol levels at doses that did not produce significant uterotropic effects.

Effect of dietary ethanol on gallbladder absorption and cholesterol gallstone formation in the prairie dog.Dietary ethanol has been reported to protect against cholesterol gallstone formation. Because enhanced gallbladder absorption of water is important in cholesterol cholelithiasis, we examined the hypothesis that ethanol acts by inhibiting the absorptive function of the gallbladder. Eighteen adult male prairie dogs were fed a lithogenic liquid diet containing 0.4% cholesterol. Half of the animals received 30% of total calories as ethanol, whereas their pair-fed controls received equicaloric amounts of maltose-dextrin. After 3 months, the gallbladders were inspected for gallstones and crystals, and gallbladder and hepatic bile were analyzed. Cholesterol stones and crystals were present in all nine controls. None of the alcohol-fed animals had stones, but four had cholesterol crystals. Gallbladder cholesterol, phospholipids, and total calcium were significantly decreased in alcohol-fed animals. In both gallbladder and hepatic bile, the cholesterol saturation index was significantly lower in alcohol-fed animals, as was the ratio of trihydroxy to dihydroxy bile salts. The ethanol-supplemented diet produced a significant decrease in the absorption of water by the gallbladder as indicated by changes in the gallbladder bile to hepatic bile ratios of the total bile salt concentration (7.29 +/- 1.25 versus 3.84 +/- 0.56; p less than 0.05) and the total calcium (3.37 +/- 0.24 versus 2.43 +/- 0.29; p less than 0.05). These findings indicate that the protective effect of ethanol may be related to its ability both to inhibit gallbladder absorption of water and to alter the composition of biliary lipids.

Soy protein concentrate and isolated soy protein similarly lower blood serum cholesterol but differently affect thyroid hormones in hamsters.There is a wide variation in the hypocholesterolemic response to ingestion of soy protein in humans. One possible explanation is that the different soy protein preparations used contain different spectra of biologically active components. This could affect a number of indices including thyroid hormone status. An increased level of thyroxine has been proposed as an underlying mechanism of the hypocholesterolemic effect of soy protein. The objective of this study was to determine if serum cholesterol and thyroid hormone concentrations differed because of feeding soy protein from different sources. Twenty-nine male weanling golden Syrian hamsters were fed rations containing 25 g/100 g protein from either isolated soy protein (ISP), soy protein concentrate (SPC) or casein for 35 d. Serum total cholesterol concentrations were lower in hamsters fed ISP and SPC compared with those fed casein (P < 0.05). No differences in cholesterol concentrations were observed in lipoprotein fractions. Serum thyroxine and free thyroxine were greater only in hamsters fed ISP than in those fed casein (P < 0.05), whereas triiodothyronine concentrations were higher in casein-fed than in SPC-fed hamsters (P < 0.05). Results indicate that protein from ISP and SPC are both effective in lowering blood cholesterol concentrations, whereas only ISP increases thyroxine concentrations. Therefore, it appears unlikely that modulation of thyroid hormone status is responsible for the cholesterol-lowering effect of soy protein.

Effects of garlic extract supplementation on blood lipid and antioxidant parameters and atherosclerotic plaque formation process in cholesterol-fed rabbits.OBJECTIVE: Possible effects of garlic extract supplementation on blood oxidant/antioxidant status, blood lipid profile and coronary plaque formation process were investigated in cholesterol-fed rabbits. METHODS: Thirty-one male rabbits of New Zealand strain were used. Twenty-two animals were given cholesterol for 4 months. Seven of them were sacrificed to investigate plaque formation and to measure blood parameters. Seven of the remaining 15 animals were fed on normal laboratory diet and others normal diet plus garlic extract for additional 3 months. Blood antioxidant and lipid parameters were measured and histological examination was made. RESULTS: Total, HDL and LDL cholesterol levels were found to be significantly higher in the Cholesterol Group relative to controls. In the histological investigation, a dense atherosclerotic plaque formation was observed in the aortas of this group. In the Normal Diet Group, total, HDL and LDL cholesterol levels were higher relative to the control group. No significant differences were observed between plaque surface areas of the Cholesterol and Normal Diet Groups. In the Extract Group however, there were differences with regard to all the analysis parameters. Total, HDL and LDL cholesterol levels were found to be decreased in this group. There was significant reduction in the plaque surface area in the aortas of this group. Blood antioxidant potential (AOP) was higher than the other groups but, malondialdehyde (MDA) level and, value of susceptibility to oxidation (SO) were lower in the Extract Group relative to the other groups. There were however no significant differences between MDA and SO values of the Control and Extract Groups. CONCLUSIONS: Our results demonstrate that cholesterol supplementation leads to dense plaque formation in the aortas of the rabbits. Garlic extract supplementation ameliorates blood lipid profile and, increases antioxidant potential. Extract treatment can significantly reduce plaque surface area in the aorta. Our results suggest that increased blood antioxidant potential due to extract supplementation might be one of the factors leading to this end.

Plasma markers of cholesterol homeostasis and apolipoprotein B-100 kinetics in the metabolic syndrome.OBJECTIVE: The metabolic syndrome is characterized by defective hepatic apolipoprotein B-100 (apoB) metabolism. Hepato-intestinal cholesterol metabolism may contribute to this abnormality. RESEARCH METHODS AND PROCEDURES: We examined the association of cholesterol absorption and synthesis with the kinetics of apoB in 35 obese subjects with the metabolic syndrome. Plasma ratios of campesterol and lathosterol to cholesterol were used to estimate cholesterol absorption and synthesis, respectively. Very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein apoB kinetics were studied using stable isotopy and mass spectrometry. Kinetic parameters were derived using multicompartmental modeling. RESULTS: Compared with controls, the obese subjects had significantly lower plasma ratios of campesterol, but higher plasma ratios of lathosterol (p < 0.05 in both). This was associated with elevated VLDL-apoB secretion rate (p < 0.05) and delayed fractional catabolism of IDL and low-density lipoprotein-apoB (p < 0.01). In the obese group, plasma ratios of campesterol correlated inversely with VLDL-apoB secretion (r = -0.359, p < 0.05), VLDL-apoB (r = -0.513, p < 0.01) and IDL-apoB (r = -0.511, p < 0.01) pool size, and plasma lathosterol ratio (r = -0.366, p < 0.05). Subjects with low cholesterol absorption had significantly higher VLDL-apoB secretion, VLDL-apoB and IDL-apoB pool size, and plasma lathosterol ratio (p < 0.05 in both) than those with high cholesterol absorption. DISCUSSION: Subjects with the metabolic syndrome have oversecretion of VLDL-apoB and decreased catabolism of apoB-containing particles and low absorption and high synthesis rates of cholesterol. These changes in cholesterol homeostasis may contribute to the kinetic defects in apoB metabolism in the metabolic syndrome.

Cholesterol metabolism in rat is affected by protocatechuic acid.The effects of protocatechuic acid on serum cholesterol and gene expression related to cholesterol metabolism in rats were investigated. Rats were fed a cholesterol-free diet with or without 5 g protocatechuic acid/kg diet for 4 wk. There were no significant differences in body weight and food intake among groups through the experimental period. The liver weight in the protocatechuic acid group was significantly lower than that in the control group. The serum total cholesterol, high-density lipoprotein (HDL)-cholesterol and very low-density lipoprotein (VLDL)+intermediate density lipoprotein (IDL)+low-density lipoprotein (LDL)-cholesterol concentrations in the protocatechuic acid group were significantly lower than those in the control group through the feeding period. The hepatic cholesterol concentration in the protocatechuic acid group was significantly higher than in the control group at the end of the 4-wk feeding period. The relative hepatic LDL receptor, apo B, apo E, lecithin-cholesterol acyltransferase (LCAT) and hepatic triglyceride lipase (HTGL) mRNA levels in the protocatechuic acid group were significantly higher than those in the control group. The results of this study suggest the possibility that the increase in the hepatic LDL receptor, apo E, LCAT and HTGL guessed by these mRNAs increase in the protocatechuic acid group lowers the serum total cholesterol level.

Association of apolipoprotein (Apo)E genotype with plasma apo E levels.The purpose of this study was to investigate the effects of apolipoprotein (apo) E genotype on plasma apo E levels as well as serum total, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride, and glucose values in 734 middle-aged and elderly, female and male subjects. Apo E allele frequencies were similar to those reported in other Caucasian populations. After adjustment for medications, alcohol use, smoking, age, and body mass index, apo E genotype was noted to have significant effects on apo E, total cholesterol, LDL cholesterol, and glucose levels in females, and on apo E, LDL cholesterol, and HDL cholesterol levels, as well as the total cholesterol (TC)/HDL cholesterol ratio in males. Female and male subjects with the apo E4 allele had significantly (P<0.05) lower plasma apo E (25 and 15%) and higher LDL cholesterol levels (5 and 2%), while those with the apo E2 allele had significantly (P<0.05) higher apo E (32 and 27%) and lower LDL cholesterol levels (10 and 10%) than the apo E3/3 group. Moreover, female apo E4 carriers had significantly (P<0.05) lower glucose values (11%) than the apo E3/3 group. These data are consistent with the concept that, in addition to the well known effects of apo E genotype on LDL-C values, this locus plays a very significant role in modulating plasma apo E levels.

Increased high-density lipoprotein cholesterol concentration in alcoholics is related to low cholesteryl ester transfer protein activity.Cholesteryl ester transfer protein (CETP) facilitates the transfer of cholesteryl esters from HDL to apoB-containing lipoproteins. Since alcoholics have high HDL cholesterol and low LDL cholesterol levels, a defect in cholesteryl ester transfer could be responsible for the alcohol-induced alteration in cholesterol distribution between lipoproteins. To test this hypothesis, we compared CETP activity in plasma from 30 alcoholics without severe liver damage and 16 control subjects. Plasma CETP activity was 28% lower in the alcoholics compared with the controls (P less than 0.001), while the teetotallers among the latter had slightly higher CETP activity than those who consumed alcohol in moderation. CETP activity increased slowly after ethanol withdrawal, but did not reach the control level within the 7-day observation period. A positive correlation was observed between plasma CETP activity and the LDL cholesterol HDL cholesterol ratio (r = 0.480, P less than 0.002), whereas CETP activity showed a negative correlation with HDL cholesterol level (r = -0.467, P less than 0.001). The results indicate that defective transfer of cholesteryl esters from HDL to LDL contributes to the high HDL cholesterol levels in alcoholics.

Low density lipoprotein receptor mRNA in rat liver is affected by resistant starch of beans.The effects of resistant starches of beans on serum cholesterol and hepatic low density lipoprotein (LDL) receptor mRNA in rats were investigated. Rats were fed a cholesterol-free diet with 150 g/kg corn starch (CS), 150 g/kg adzuki (Vigna angularis) starch (AS), 150 g/kg kintoki (Phaseolus vulgaris, variety) starch (KS), or 150 g/kg tebou (P. vulgaris, variety) starch (TS) for 4 wk. There were no significant differences in body weight among groups through the experimental period. The liver weight in the CS group was 1.1-1.2 times higher than that in the AS, KS, and TS groups. The cecum weight in the TS was 1.4 times higher than that in the CS group, and the cecal pH in the CS group was significantly higher than in the other groups. The serum total cholesterol, very low density lipoprotein + intermediate density lipoprotein + LDL-cholesterol and high density lipoprotein (HDL)-cholesterol concentrations in the bean starch groups were significantly lower than those in the CS group through the feeding period. The total cholesterol/HDL-cholesterol ratio in the bean starch groups was also significantly lower than that in the CS group at the end of the 4-wk feeding period. The hepatic cholesterol concentration in the TS group was significantly higher than in the CS group at the end of the 4-wk feeding period. The relative quantity of hepatic apo B mRNA in the AS group was 1.2 times higher than that in the CS group, and the hepatic LDL receptor mRNA levels in the AS and TS groups were 1.8-2.0 times higher than that in the CS group. The results of this study demonstrate that AS, KS, and TS lowered the serum total cholesterol level by enhancing the hepatic LDL receptor mRNA level.