Cholesterol Metabolism In Hamsters Research Articles

Fatty acid moieties have little effect on cholesterol‐lowering potency of plant sterol esters

Plant sterol esters are the popular cholesterol‐lowering dietary supplements. In order to understand the role of fatty acid moieties in the cholesterol‐lowering activity of plant sterol esters, the present study was to: (i) compare the cholesterol‐lowering activity of sterol esters of sunflower oil (SSF) with that of sterol esters of canola oil (SCO); and (ii) to systematically investigate the effect of SSF and SCO on the gene expression of sterol transporters, enzymes, receptors and proteins involved in cholesterol metabolism in hamsters fed a high cholesterol diet. GC analysis showed that SSF and SCO had similar sterol profile but they had different fatty acid moieties. Results showed both SSF and SCO could equally reduce plasma cholesterol in a dose‐dependent manner. Both SSF and SCO could inhibit the cholesterol absorption and enhance the excretion of bile acids. In the similar ways, dietary SSF and SCO could up‐regulate hepatic cholesterol‐7α‐hydroxylase (CYP7A1) and down‐regulate intestinal sterol transporter Niemann‐Pick C1‐like 1 (NPC1L1), acyl coenzyme A: cholesterol acyltransferase 2 (ACAT2) and hepatic 3‐hydroxy‐3‐methylglutaryl‐CoA reductase (HMG‐CoA reductase). It was concluded that the fatty acid moieties had little effect on the cholesterol‐lowering activity of SSF and SCO.Practical applications: Plant sterols are effective in reducing plasma cholesterol. Commercially, plant sterol esters of sunflower oil and plant sterol esters of canola oil are mostly used for this purpose. The present study found that SSF and SCO were equally effective in reducing plasma cholesterol in a dose‐dependent manner regardless the significant difference in their fatty acid compositions.Fatty acid moieties have little effect on cholesterol‐lowering potency of plant sterol esters.

Effects of dietary hull-less barley β-glucan on the cholesterol metabolism of hypercholesterolemic hamsters

The aim of the present study is to investigate the hypocholesterolemic effects of dietary hull-less barley β-glucan (HBG) on cholesterol metabolism in hamsters which were fed a hypercholesterolemic diet. The hamsters were divided into 3 groups and fed experimental diets, containing 5‰ HBG or 5‰ oat β-glucan (OG), for 30days. The HBG, as well as OG, lowered the concentration of plasma LDL-cholesterol significantly. The excretion of total lipids and cholesterol in feces were increased in HBG and OG groups compared with the control group. The activity of 3-hydroxy-3-methyl glutaryl-coenzyme A (HMG-CoA) reductase in liver was reduced significantly in the HBG group compared with the control and OG groups. The activity of cholesterol 7-α hydroxylase (CYP7A1) in the liver, in the HBG and OG groups, was significantly increased compared with the control group. The concentrations of acetate, propionate and total short chain fatty acids (SCFAs) were not significantly different between the HBG and control groups. These results indicate that dietary HBG reduces the concentration of plasma LDL cholesterol by promoting the excretion of fecal lipids, and regulating the activities of HMG-CoA reductase and CYP7A1 in hypercholesterolemic hamsters.

Effects of trans-10,cis-12 conjugated linoleic acid on cholesterol metabolism in hypercholesterolaemic hamsters

Conjugated linoleic acid (CLA) has received great attention in recent years because of its pleiotropic biological activities, but considerably fewer studies have been published addressing its role in serum lipids and atherosclerosis compared to other topics covered. The aim of the present study was to assess the effects of the trans-10,cis-12 isomer of CLA on cholesterolaemia and on several metabolic pathways involved in cholesterol metabolism in hamsters. Animals were fed atherogenic diets supplemented with 0.5% linoleic acid, 0.5% trans-10,cis-12 CLA or 1.0% trans-10,cis-12 CLA, for 6 weeks. Serum lipoproteins were separated by FPLC. Cholesterol in serum and liver, as well as triacylglycerols and phospholipids in liver were assessed by spectrophotometry. 3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoAR), acyl-coenzyme A:cholesterol acyltransferase (ACAT) and cholesteryl ester hydrolase (CEH) activities were measured by radiometry, and LDL receptors were determined by Western blot. trans-10,cis-12 CLA feeding did not modify food intake nor final body weight. Although serum total cholesterol remained unchanged, when cholesterol fractions were analyzed a significant decrease in VLDL-cholesterol was observed in CLA-fed animals, without changes in HDL-cholesterol or LDL-cholesterol. trans-10,cis-12 CLA decreased cholesterol ester content and increased free cholesterol in liver. The activity of HMGCoAR was not modified. In contrast, ACAT activity was reduced by both CLA doses and CEH was increased by the high CLA dose. LDL receptors were significantly reduced by trans-10,cis-12 feeding when expressed as arbitrary units per mg of protein, however, the total receptor mass remained unchanged. These results suggest that, under the present experimental conditions, trans-10,cis-12 CLA feeding reduces cholesterol esterification in liver and decreases the minority serum VLDL-cholesterol fraction, but it does not show a hypocholesterolaemic effect. A dose-response effect was not observed.

Effects of a novel pomace fiber on lipid and cholesterol metabolism in the hamster

Water-insoluble fiber-rich fraction (WIFF) was isolated from the pomace of Averrhoa carambola, which is popular in Asia. The effects of WIFF-added diet on the lipid and cholesterol metabolism in hamsters were investigated and compared with those of cellulose-added and fiber-free diet as controls. Experimental results showed that the consumption of carambola WIFF decreased ( P < 0.05) the concentrations of serum triacylglycerol, serum total cholesterol, and liver cholesterol, and increased ( P < 0.05) the concentrations of fecal total lipids, fecal cholesterol, and fecal bile acids. The intake of WIFF also increased the fecal bulk and moisture. These pronounced cholesterol- and lipid-lowering effects of WIFF might be attributed to its ability to enhance the excretion of cholesterol and bile acids via feces. Our results suggested that carambola WIFF is used as a promising cholesterol-lowering ingredient in human diets or new formulations of fiber-rich functional foods.

Effect of a modified milk fat and calcium in purified diets on cholesterol metabolism in hamsters

Modification of milk fat both by partially replacing saturated FA with oleic acid (18:1) and by increasing calcium intake independently reduces plasma cholesterol. Whether modification of both factors together would synergistically reduce plasma cholesterol is unknown. Seventy-two male golden Syrian hamsters were separated into four diet treatment groups (n = 18/group) and fed ad libitum for 7 wk. Diets contained either modified milk fat (MMF) or regular milk fat (RMF) with either 0.5% (MMF and RMF) or 1.3% calcium (w/w) (MMFC and RMFC). All diets contained 11% test fat, 4% soybean oil, and 0.15% cholesterol (w/w). During the last week, feces were collected for three consecutive days for analysis of fecal FA, cholesterol, and calcium excretion. Overnight-fasted animals were sacrificed, and plasma and livers were collected for lipid analysis. Neither MMF nor additional calcium significantly affected plasma lipids. However, significant interactions existed between MMF and additional calcium for the ratio of LDL cholesterol to HDL cholesterol (LDL/HDL), indicating that increased calcium intake reduced this ratio only in RMF animals. In addition, MMF reduced LDL/HDL relative to RMF. MMF significantly increased hepatic total and esterified cholesterol. Additional calcium significantly increased fecal calcium and saturated FA (SFA) excretion, whereas MMF significantly reduced SFA excretion. RMFC induced the highest excretion of 16:0 among all groups. Replacement of SFA with 18:1 in the MMF reduced the impact of high calcium on LDL/HDL. Additional calcium reduced LDL/HDL only in the presence of RMF, which may be achieved through an increased excretion of 16:0.

Effect of taurine on cholesterol metabolism in hamsters: Up-regulation of low density lipoprotein (LDL) receptor by taurine

The effects of taurine on hepatic cholesterol metabolism were investigated in hamsters fed a high-fat diet or normal chow. Two weeks-treatment of taurine at 1% in drinking water prevented high-fat diet-induced increase in cholesterol levels of serum and liver. The decrease in serum cholesterol by taurine was due to decrease in non-HDL cholesterols. A similar tendency was noted in serum and liver cholesterol levels of hamsters fed a normal diet. In hamsters fed a high-fat diet, taurine prevented elevation in hepatic activity of acyl-CoA:cholesterol acyltransferase (ACAT) and increased the activity of cholesterol 7α–hydroxylase. Taurine also increased cholesterol 7α–hydroxylase activity in hamsters fed normal chow. Studies on liver membranes revealed that taurine increased 125I–labeled LDL binding by 52% and 58% in hamsters fed either a normal chow or high-fat diet, respectively. Furthermore, LDL kinetic analysis showed that taurine intake resulted in significant faster plasma LDL fractional catabolic rates (FCR). These results suggest that taurine elevates hepatic LDL receptor and thereby decreases serum cholesterol levels, an event which may be the result of hepatic cholesterol depletion as a consequence of increased bile acid synthesis via enhancement of cholesterol 7α–hydroxylase activity. Thus, up-regulation of the LDL receptor and subsequent increase in receptor-mediated LDL turnover may be a key event in the cholesterol-lowering effects of taurine in hamsters.

The effect of dietary casein and soyprotein on cholesterol metabolism in hamsters

The effect of dietary casein and soyprotein on cholesterol metabolism in hamsters

Metabolism of 7 beta-alkyl chenodeoxycholic acid analogs and their effect on cholesterol metabolism in hamsters.

The metabolism of 7-ethyl- and 7-propyl-chenodeoxycholic acids was studied in hamsters. Both bile acid analogs were absorbed efficiently by the intestine and secreted into the bile at rates similar to those of chenodeoxycholic acid. After intraduodenal administration into bile fistula hamsters, the 7-alkyl analogs were present in bile as the glycine and taurine conjugates. The glycine/taurine ratios were: chenodeoxycholic acid, 1.9; 7-ethyl analog, 0.3; and 7-propyl analog, 0.2. After oral administration, during a 21-day feeding experiment, the 14C-labeled analogs were recovered quantitatively in the feces. Chenodeoxycholic acid was largely 7-dehydroxylated to lithocholic acid in the intestinal tract. In contrast, the 7 alpha-hydroxy group of the 7-alkyl bile acids was completely resistant to bacterial action. 7-Ethyl-chenodeoxycholic acid was transformed in part to a compound tentatively identified as 7 alpha-hydroxy-3-oxo- 7 beta-ethyl-5 beta-cholanoic acid while 7-propyl-chenodeoxycholic acid was excreted unchanged. In the hamsters used, the 7-alkyl bile acid analogs did not inhibit the bacterial dehydroxylation of chenodeoxycholic acid. At the end of the 21-day feeding period, analysis of the gallbladder bile showed that 7-methyl-, 7-ethyl-, and 7-propyl-chenodeoxycholic acids accounted for 38, 31, and 12% of total bile acids, respectively. The 7-alkyl bile acids decreased cholesterol absorption; the 7-propyl analog caused significant decrease in serum and liver cholesterol concentration. These experiments demonstrate that the 7-ethyl- and 7-propyl chenodeoxycholic acids, just like the 7-methyl-analog, are absorbed by the intestine and participate in the enterohepatic circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Plant cell walls and monogastric diets

A brief summary is given of the recent and progressing research at the Swedish University of Agricultural Sciences in development of analytical methodology for plant cell wall components (dietary fiber) and mixed-linkage β-glucans. Applications of the methods for the chemical characterization of various types of human and monogastric animal foods will be presented, including heat-processed, starch-rich foods. In the latter group Maillard reaction products, “resistant starch” and chemically transformed starch increase the dietary fiber values. Nutritional studies on the role and properties of plant cell wall materials in connection with bile acid and cholesterol metabolism in hamster and with digestion of pig and poultry diets will be discussed.

Effect of 7-methylated bile acids and bile alcohols on cholesterol metabolism in hamsters.

The effect of 7-methyl substituted bile acid and bile alcohol analogues on cholesterol metabolism was studied in the hamster. Animals were fed chow plus 0.1% cholesterol supplemented with 0.1% of one of the following steroids: chenodeoxycholic acid, 7-methyl-chenodeoxycholic acid, 7 beta-methyl-24-nor-5 beta-cholestane-3 alpha, 7 alpha, 25-triol, cholic acid, 7-methyl-cholic acid, or 7 beta-methyl-24-nor-5 beta-cholestane-3 alpha, 7 alpha, 12 alpha,25-tetrol. Cholesterol absorption was determined from fecal analysis after feeding of radiolabeled cholesterol and beta-sitosterol. Of the six compounds studied, chenodeoxycholic acid and 7-methyl-chenodeoxycholic acid decreased intestinal cholesterol absorption (17% and 31% decrease, respectively). Only 7-methyl-chenodeoxycholic acid decreased serum cholesterol concentration (29% decrease), but there were no analogous changes of liver and biliary cholesterol concentration and cholesterol saturation of bile. Total fecal neutral sterol excretion was increased in the groups fed chenodeoxycholic acid and 7-methyl-chenodeoxycholic acid. In addition, the production of coprostanol was increased in both groups. These data suggest that 7-methyl-chenodeoxycholic acid resembles chenodeoxycholic acid in its effect on cholesterol metabolism and may be a potential candidate for further studies of its gallstone-dissolving properties.

Effect of cholesterol and bile acids on the regulation of cholesterol metabolism in hamster

Cholesterol metabolism studies were carried out in the golden Syrian hamster ( Mesocricetus auratus) fed a chow diet supplemented with cholesterol, bile acids or both for 1 month. Addition of cholesterol (0.15 or 1%) to the chow diet produced dose-related increases in plasma and liver cholesterol and lowered hepatic microsomal hydroxymethylglutaryl-CoA reductase activity by 90%. Supplementation of the stock diet with 2% cholestyramine reduced plasma cholesterol by 20% and caused a 5-fold increase in hydroxymethyl-glutaryl-CoA] reductase activity. The cholesterol diets increased the proportion of chenodeoxycholic acid in bile at the expense of cholic acid while cholestyramine had the opposite effect. The lithogenic index of bile increased significantly during the cholesterol and cholestyramine regimens, but remained well below 1.0. Addition of 0.1% bile acid to the stock diet (0.01% cholesterol) produced significant increases in plasma cholesterol in the chenodeoxycholic acid and cholic acid groups and in liver cholesterol in the cholic acid group. Hepatic hydroxymethylglutaryl-CoA reductase was significantly depressed only in the cholic acid group. The effects of ursodeoxycholic acid on plasma and liver cholesterol were not significant. The administered bile acids predominated in bile. The chenodeoxycholic acid and ursodeoxycholic acid groups showed a significant increase in biliary lithocholic acid. More lithocholic acid formed from chenodeoxycholic acid than from ursodeoxycholic acid. The lithogenic index increased in the chenodeoxycholic acid and cholic acid groups but remained below 1.0. In animals on the 0.15% cholesterol diet ursodeoxycholic acid prevented the accumulation of cholesterol in plasma and liver to a moderate extent, while chenodeoxycholic acid reduced liver cholesterol only. Hepatic hydroxymethylglutaryl-CoA reductase was very low on the 0.15% cholesterol diet and was not reduced further by dietary bile acids. Animals on the 0.15 or 1% cholesterol diets had smaller proportions of secondary bile acids (deoxycholic acid and lithocholic acid) in bile than did hamsters on the chow diet. The lithogenic index was below 1.0 in all groups, but was lowest with the ursodeoxycholic acid regimen. The dietary bile acids had relatively little effect on endogenous bile acid and neutral sterol production in hamsters on high cholesterol intakes. Cholesterol absorption averaged about 60% on the 0.15% cholesterol control diet and on the same diet with added cholic acid. Ursodeoxycholic acid and chenodeoxycholic acid reduced the absorption but the difference from the controls was significant with ursodeoxycholic acid only. Under the conditions employed, the effect of bile acids on cholesterol metabolism in the hamster depends on the cholesterol content of the diet.

Cholesterol metabolism in hamsters reared on diets with different effects on gallstone formation

The incorporation of labeled acetate into cholesterol and the elimination of labeled cholesterol from the body was studied in three groups of hamsters reared on diets with known effects on gallstone formation in young individuals of this species. One group of hamsters received a diet producing abundant formation of cholesterol gallstones. This diet consisted of casein, 20%; glucose, 74.3%; plus salts, vitamins and choline chloride. A second group of hamsters received a diet which induced only a slight tendency to gallstone formation (or none at all). This diet differed from that of the first group by having rice starch instead of glucose as the carbohydrate component. The third group received a diet that has previously been found capable of bringing already-formed cholesterol gallstones into solution in the hamster. This (“curative”) diet differed from those given to the two other groups in that the 74.3% carbohydrate was replaced by 28.3% ground white rice, 36% dried yeast and 10% lard; further, the salt mixture contained added cupric sulfate. The per cent incorporation of intraperitoneally injected [1- 14C] acetate into cholesterol 70 ± 5 min after the injection was about 1.2% in the group given the glucose diet, about 0.15% in the group given the rice-starch diet, and about 0.4% in the group given the “curative” diet. The per cent incorporation remained higher in the group given the glucose diet than in the other two groups during the entire period during which measurements were made (up to 5 h). In the groups used for the incorporation study, the average contents of total cholesterol in the body, as mg per 100 g body weight, were 223 ± 13 for 8 animals in the group on the glucose diet, 166 ± 6 for 9 animals on the rice-starch diet, and 162 ± 6 for 8 animals on the “curative” diet. The rates of elimination of intraperitoneally injected [4- 14C]cholesterol in the three groups were compared by determination of the radioactivity of the total body cholesterol in animals killed 0, 2, 7 and 14 days after the injection. There was no significant difference between the three groups with respect to the time (10–12 days) required to bring the content of radioactive cholesterol down to 50% of the amount recovered immediately after the injection.