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1.
Bertram I. Cohen Takahiro Mikami Nariman Ayyad Yasuko Mikami Erwin H. Mosbach 《Lipids》1995,30(4):299-305
The type of dietary fat strongly affects the incidence of gallstones in the hamster model of cholesterol cholelithiasis. The
present study was designed to determine whether dietary fats could affect gallstone formation by altering the microstructure
(vesicular/micellar ratio) of cholesterol in bile. Golden Syrian hamsters from Sasco (Omaha, NE) or Charles River (Wilmington,
MA) were fed nutritionally adequate semipurified diets to which were added: (i) 4.0% butterfat without added cholesterol;
(ii) 1.2% palmitic acid plus 0.3% cholesterol; or (iii) 4.0% safflower oil plus 0.3% cholesterol. Gallstone incidence and
the percentage of cholesterol in vesicles and micelles were determined after two- or six-week feeding periods. Three out of
ten Sasco hamsters fed the 1.2% palmitic acid diet for two weeks had cholesterol stones, while none of the eight Charles River
animals had stones. In the Sasco hamsters, a significant proportion of the biliary cholesterol was found in void volume vesicles
(28.8%) and small vesicles (17.1%); Charles River hamsters had negligible proportions (1.1%) of cholesterol in void volume
vesicles and 15.4% in small vesicles. Cholesterol gallstones were most abundant in Sasco hamsters fed 1.2% palmitic acid for
six weeks (nine out of ten animals); the mean cholesterol saturation index of the bile was 1.27. A significant proportion
of the biliary cholesterol was eluted in the void volume vesicles (21.4%) and in small vesicles (15.0%). Five of the eight
identically treated Charles River hamsters had cholesterol stones; the cholesterol saturation index averaged 1.36, and the
biliary cholesterol was present in void volume vesicles (31.3%) and small vesicles (14.3%). Vesicles were not detected in
the bile of hamsters fed cholesterol-free diets, and none of these animals developed cholesterol gallstones. Safflower oil
diets inhibited stone formation even though the cholesterol saturation index was above unity. After six weeks, biliary cholesterol
transported in void volume vesicles was highest for Sasco hamsters (13.3%) as compared to Charles River animals (6.9%), but
total cholesterol transported in void volume vesicles plus small vesicles was similar in both groups (33.5% vs. 26.2%), respectively.
These results suggest that in both strains of hamsters dietary fat influences gallstone formation by modulating the vesicular/micellar
distribution of biliary cholesterol. Apparently, the presence of cholesterol/phospholipid vesicles in bile is associated with
cholesterol gallstone formation. 相似文献
2.
Takahiro Mikami Bertram I. Cohen Yasuko Mikami Nariman Ayyad Erwin H. Mosbach 《Lipids》1994,29(8):529-534
The distribution of cholesterol among its carriers was studied in the bile of male and female hamsters. Sasco hamsters (Sasco
Inc., Omaha, NE) were fed a semipurified diet with 0.0% cholesterol and 4% butterfat (group 1, males; group 4, females); a
semipurified diet with 0.3% cholesterol and 1.2% plamitic acid (group 2, males; group 5, females); and a semipirified diet
with 0.3% cholesterol and 4% safflower oil (group 3, males; group 6, females). At the end of six weeks, gallstones were found
only in male hamsters receiving both cholesterol and dietary fat (fatty acid) (incidence of cholesterol stones: 90% in group
2; 22% in group 3). The biliary cholesterol carriers were separated and isolated from the bile of the hamsters by gel filtration
chromatography, using the method of Pattinson [Pattinson, N.R., Willis, K.E., and Frampton, C.M. (1991)J. Lipid Res. 32, 205–214]. In those male hamsters that formed cholesterol gallstones, significant amounts of cholesterol were present in
the void volume which contained large cholesterol phospholipid vesicles (void volume vesicles) (23% in group 2 and 15% in
group 3). Smaller cholesterol/phospholipid vesicles were eluted next (fractions 30–45) and contained 15% of biliary cholesterol
in group 2 and 21% in group 3. The remainder of the cholesterol was associated with mixed cholesterol/phospholipid/bile salt
micelles. The cholesterol/phospholipid ratio was larger in both the void volume vesicles and small vesicles (2.40 and 1.48
in group 2; 2.56 and 1.33 in group 3, respectively) compared to the micelles (about 0.3 in groups 2 and 3). In contrast, the
bile of the female hasmters contained few vesicles (3% small vesciles in group 5) and the cholesterol/phospholipid ratio of
these vesicles was lower (0.94). Hamsters fed cholesterol-free diets (groups 1 and 4) had no biliary cholesterol/phospholipid
vesilces; and cholesterol was present in micelles. The results suggest that both the gender and the diet of the hamsters affected
the distribution of biliary cholesterol between vesicles and micelles. The development of cholelithiasis in this animal model
appears to depend on the rapid nucleation of cholesterol-rich phospholipid vesicles in bile. 相似文献
3.
Cholesterol gallstone induction in hamsters reflects strain differences in plasma lipoproteins and bile acid profiles 总被引:4,自引:4,他引:0
Because different strains of hamsters vary in their susceptibility to gallstones, the relationship between plasma lipoproteins,
hepatic cholesterol, bile lipids and bile acid profile was examined during gallstone induction in strains of male Syrian hamsters
from Charles River Lakeview (CHR), Biobreeder F1B (BIO) and Harlan Sprague-Dawley (HAR). Gallstones were induced by feeding a purified diet containing 0.4 or 0.8% cholesterol
for 5 wk. Basal plasma total cholesterol was similar, but the hypercholesterolemia induced by dietary challenge was significantly
lower in CHR than in HAR and BIO hamsters. Cholesterol-fed CHR hamsters transported cholesterol mainly in HDL (47%), whereas
VLDL-C+IDL-C predominated in BIO and HAR hamsters, and their HDL transported only 28 and 38%, respectively. HAR hamsters accumulated
the most hepatic cholesterol, revealed the highest cholate/cheno ratio, the lowest glycine/taurine ratio and hydrophobicity
index. HAR also developed the fewest cholesterol gallstones (23%), while 64% of CHR and 58% of BIO hamsters had cholesterol
gallstones and 34% of BIO hamsters developed pigment stones. Doubling dietary cholesterol from 0.4 to 0.8% doubled the incidence
of cholesterol gallstones but exerted minimal impact on other parameters compared to strain differences. Thus, different strains
of hamsters vary considerably with respect to biliary cholesterol, bile acid profile and formation of cholesterol gallstones
associated with differences in plasma lipoprotein profiles. 相似文献
4.
Cholesterol gallstones were produced in young male, golden Syrian hamsters, obtained from three different suppliers, by administering
a nutritionally adequate, semipurified diet for periods of either 5 or 10 weeks. The major components of the lithogenic diet
were casein, cornstarch, butterfat, corn oil and 0.3% cholesterol. The hamsters were obtained from Sesco, Harlan Sprague-Dawley
(Engle hamster) and Charles River (Lakeview hamster). There were profound differences among the three groups with respect
to gallstone formation and cholesterol metabolism: The highest incidence of gallstones occurred in Sesco hamsters, 44.4% and
63.6% after 5 and 10 weeks on the lithogenic diet, respectively. In the Engle hamster, after a 5-week feeding, cholesterol
crystals and gallstones were absent. When the feeding period was extended to 10 weeks, cholesterol gallstones were present
in 45.5% of the animals. In the Lakeview hamsters, neither gallstones nor cholesterol crystals were found in the gallbladder
after a 5-week period. After 10 weeks, cholesterol gallstones were found in only a single hamster. In all groups, the lithogenic
diet produced large increases of liver, serum and biliary cholesterol concentrations and increased liver weights. When the
animals were fed for 5 weeks, only the bile of Sesco hamsters became supersaturated. Supersaturated bile was induced in all
groups after a 10-week feeding of the lithogenic diet with cholesterol saturation ranging from 1.47 to 1.97. These data indicate
that it is possible to induce cholesterol gallstones in hamsters by means of a nutritionally adequate, semipurified diet of
moderate cholesterol content. The source of the animals appears to be an important variable, because there were significant
differences among the hamsters of differing origins, in cholesterol metabolism and rates of gallstone formation. 相似文献
5.
Bertram I. Cohen Nariman Ayyad Takahiro Mikami Yasuko Mikami Erwin H. Mosbach 《Lipids》1994,29(7):503-508
Sterol balance studies, using both isotopic and chromatographic techniques, were carried out in hamsters fed semipurified
diets to detect changes in sterol metabolism during the early period of the lithogenic stimulus. The balance studies examined
animals in the first two weeks on the experimental lithogenic diets. The variables were as follows: dose of cholesterol (group
1, 0.05% vs. group 2, 0.2%); dietary fat (fatty acid) (group 2, butterfat vs. group 4, palmitic acid); source of hamster [group
2, Sasco (Omaha, NE) vs. group 3, Charles River (Wilmington, MA)]; average weight of animals (group 4, 60 g vs. group 5, 119
g). Animals in groups 1, 2, 3 and 5 maintained almost constant weight throughout the two-week balance study. Liver and plasma
cholesterol levels increased in groups 2–5 with increasing dose of dietary cholesterol. The highest levels were found in group
4 (liver cholesterol, 32.7 mg/g; plasma cholesterol, 367 mg/dL). Sterol balance measurements showed that bile acid synthesis
remained low (range 0.55–1.01 mg/d) for all groups regardless of the intake of dietary cholesterol (range, 3.27–20.90 mg/d).
The dietary cholesterol absorbed from the intestine (range, 2.91–18.91 mg/d) was stored in the liver; this storage was reflected
in the negative values for cholesterol balance for all groups (range, −0.70 to −14.97 mg/d). These studies did not reveal
any correlations between parameters of sterol balance and cholelithiasis. 相似文献
6.
In an established hamster model of cholesterol cholelithiasis, a semipurified lithogenic diet containing 4% butterfat and
0.3% cholesterol leads to the production of cholesterol gallstones in only 50–60% of animals after a 6-wk feeding period.
The purpose of this study was to investigate whether gallstone incidence could be increased while feeding a nutritionally
adequate diet of moderate cholesterol content. The semipurified lithogenic diet was modified as follows: (i) substitution
of 1.2% palmitic acid for 4% butterfat, and (ii) varying the amount of dietary cholesterol from 0.0 to 0.3% with either butterfat
or palmitic acid as the lipid component of the diet. Substitution of palmitic acid for butterfat produced a significantly
higher incidence of cholesterol gallstones (94%vs. 53%). Palmitic acid also raised the incidence of gallstones when added to the 0.1% and 0.2% cholesterol diets as compared
to butterfat: 0%vs. 44% and 50%vs. 81%, respectively. Gallstone incidence increased from 0% to nearly 100% when the cholesterol content of the palmitic acid
diets was raised from 0.0% to 0.3%, indicating a dose response effect with respect to dietary cholesterol. Hamsters fed cholesterol-free
diets did not form gallstones. Increased dietary cholesterol led to increased liver weight associated with a significant increase
in liver cholesterol concentration. However, the palmitic acid groups had significantly lower liver cholesterol values than
the corresponding butterfat groups. Serum and biliary cholesterol concentrations increased with increasing dietary cholesterol
intake, but there were no differences between the butterfat and palmitic acid groups. The cholesterol saturation index increased
from 0.56 to 1.32 in the butterfat groups and from 0.56 to 1.30 in the palmitic acid groups upon raising the dietary cholesterol
from 0.0 to 0.3%. Biliary total bile acid concentration did not vary significantly within all groups; however, the addition
of cholesterol produced an increase in the ratio of chenodeoxycholic acid to cholic acid. It is concluded that in Sasco hamsters
the saturated fatty acid, palmitic acid, when substituted for butterfat in a nutritionally adequate lithogenic diet, is capable
of increasing gallstone incidence to almost 100% during a 6-wk feeding period. 相似文献
7.
M. A. Sullivan-Gorman J. M. Anderson N. M. DiMarco J. Johnson I. Chen J. Ashby G. U. Liepa 《Journal of the American Oil Chemists' Society》1987,64(8):1196-1199
The objective of this experiment was to study the effects of dietary cottonseed protein and casein on plasma and biliary lipids,
plasma amino acids and gallstones in hamsters. Thirty-four male hamsters (60 ± 5 g) were fed either the lithogenic “Dam Diet”
(containing 20% casein, 74.3% sucrose and 5.7% vitamin-mineral mix) or a similar diet that contained 20% cottonseed protein
for 30 days. Both diets contained protein as a protein isolate. The concentration of alpha-aminobutyric acid was significantly
elevated in the casein-fed group. Significant differences in the total plasma cholesterol or lipoprotein cholesterol concentrations
were not observed between the two dietary groups.
A significant elevation in the absolute concentration of biliary cholesterol was observed in the casein-fed hamsters. Cottonseed
protein-fed animals exhibited a significantly elevated concentration of bile acids. The ratio of glycochenodeoxycholic:glycocholic
acid was significantly higher in the cotton-seed protein-fed group. This study reports that an elevated concentration of biliary
cholesterol with a concomitant decrease in bile acid concentration yields a condition favorable to gallstone formation. It
is proposed that cottonseed protein may have a specific effect on the bile acid pool by increasing the ratio of glycochenodeoxycholic
acid:glycocholic acid which, in turn, prevents formation of cholesterol gallstones. 相似文献
8.
Male Syrian hamsters (60–70 g) were fed purified diets containing 5% fat (American Fat Blend) and 15% fiber with or without
0.3% cholesterol (0.86 mg/kcal), for 12 weeks. Hamsters fed the cholesterol-supplemented challenge diet revealed a major increase
in plasma triglyceride between 9 and 12 weeks, whereas plasma cholesterol (which reflected body weight dynamics) increased
three-fold up to nine weeks and plateaued (342±22vs. 122±5 mg/dL). The greatest increases in cholesterol occurred in the very low density lipoprotein (VLDL) and high density
lipoprotein (HDL2) fractions. Gallstone incidence was similar (69%vs. 78%) for cholesterol-supplementedvs. control hamsters, but the type of stones differed. Of the cholesterol-supplemented hamsters with gallstones, 45% had cholesterol
stones and 55% had pigment stones. Only pigment stones were seen in control hamsters. Hamsters with cholesterol stones were
25% heavier and transported most cholesterol in VLDL (33±5%), approximately double that in VLDL of cholesterol-supplemented
hamsters with no stones (19±3%) or cholesterol-supplemented hamsters with pigment stones (21±3%). Hamsters with pigment stones
or no stones (regardless of diet fed) transported the majority of their cholesterol in HDL2 (44%), whereas this figure was only 27% in hamsters that developed cholesterol stones. Thus pigment stones develop routinely
in hamsters fed casein-based purified diets. Adding dietary cholesterol resulted in cholesterol gallstones only in those hamsters
that gained the most weight and whose terminal VLDL/HDL cholesterol ratio exceeded 1.0, not unlike the lipoprotein profile
of obese humans who develop cholesterol gallstones.
Presented in part at the Xth International Symposium on Drugs Affecting Lipid Metabolism, November 8–11, 1989, Houston, TX. 相似文献
9.
Bertram I. Cohen Erwin H. Mosbach Nariman Ayyad Shigeo Miki Charles K. McSherry 《Lipids》1992,27(7):526-532
We tested two hypotheses, i) whether the type and the amount of fat in the diet will affect the formation of cholesterol gallstones
in the hamsters, and ii) whether palmitic acid, a major fatty acid component of butterfat, can act as a potentiator of cholesterol
cholelithiasis in the hamster. Young, male golden Syrian hamsters (Sasco) were fed a semipurified diet containing casein,
corn starch, cellulose and cholesterol (0.3%) to which various types and amounts of fat (butterfat, olive oil, menhaden oil,
corn oil) were added. All diets contained 2% corn oil to supply essential fatty acids to the growing hamsters. No deaths or
illness occurred during the experiment. Animals fed the semipurified diet plus 4% butterfat (group 1) had a gallstone incidence
of 63%. Replacement of butterfat with either olive oil, corn oil or menhaden oil prevented the formation of cholesterol gallstones
entirely (groups 2–4). When total butterfat was increased from 4% to 8% (group 8), the incidence of cholesterol gallstones
increased to 80%. Substitution of 4% olive oil (group 5), corn oil (group 6), or menhaden oil (group 7) for the additional
4% butterfat significantly reduced gallstones to 35%, 45% and 30%, respectively. The replacement of 4% butterfat with 1.2%
palmitic acid gave the highest incidence of cholesterol gallstones (95%). These results suggest that butterfat (and one of
its components, palmitic acid) intensifies gallstone formation in this model whereas mono- and polyunsaturated fats act as
inhibitors of cholesterol cholelithiasis. A fatty acid, possibly palmitic acid, appears to act as lithogen in our model. 相似文献
10.
This study examined the effect of castration and dietary hormonal supplementation on cholesterol cholelithiasis in male hamsters.
Animals fed a standard lithogenic diet developed cholesterol gallstones (17%) after 6 wk, while castrated hamsters did not
form any stones. Addition of a synthetic androgen, methyltestosterone, to the lithogenic diet induced cholelithiasis in castrated
animals (50%). The biles of normal and castrated-hormone supplemented hamsters had cholesterol saturation indices of 1.0 and
1.1, respectively, while the bile of the castrated animals remained unsaturated (0.6). The ratio of cholic acid/chenodeoxycholic
acid in bile increased after castration, but returned to normal levels following hormonal supplementation. Biliary cholesterol
carriers were separated by ultracentrifugation. Animals in the stone-forming groups (normal and castrated-hormone treated)
had a significant proportion of their biliary cholesterol in vesicles (44 and 46%, respectively); castrated hamsters had less
cholesterol in vesicle form (9%). The molar ratio of cholesterol/phospholipid in vesicles was reduced after castration (0.93
vs. 0.42) and increased by hormonal supplementation (1.89). In conclusion, when compared to normal male hamsters fed a standard
lithogenic diet, castration reduced the cholesterol saturation of bile, lowered the vesicular/micellar ratio in bile, and
inhibited cholesterol cholelithiasis. Dietary androgen supplementation increased the lithogenicity of bile, resulting in stone
formation in castrated animals. 相似文献
11.
Dietary fat alters biliary lipid secretion in the hamster 总被引:1,自引:0,他引:1
Dietary fat has been found to alter the incidence of cholesterol gallstones in hamsters: butterfat intensifies while safflower
oil reduces lithiasis. We now report how dietary fat affects bile flow and biliary lipid secretion in this model. Male hamsters
were fed one of three experimental diets: a control diet (containing 0.3% cholesterol); control diet +4.0% butterfat; or control
diet +4.0% safflower oil. After three weeks, bile samples were collected via an external biliary fistula. The endogenous bile
acid pool was depleted for 120 min followed by increasing rates of taurocholate infusion for 160 min. Basal secretion of biliary
lipids was measured during the bile acid depletion period. Basal bile flow and bile acid output were not significantly different
in the three groups. Dietary butterfat increased basal cholesterol output compared to the control diet (0.037 vs. 0.025 μmol/min·kg,
respectively); safflower oil did not change cholesterol output (0.027 μmol/min·kg). Hamsters fed butterfat or safflower oil
secreted more phospholipid (0.171 and 0.178 μmol/min·kg, respectively) than controls (0.131 μmol/min·kg). The cholesterol/phospholipid
output ratio of the butterfat group was higher than the safflower oil group (0.220 vs. 0.153, respectively). Effects of dietary
fat on several relationships between bile flow and biliary lipid secretion were analyzed by linear regression using the data
for the entire bile collection period (bile acid depletion and taurocholate infusion). Butterfat and safflower oil did not
change either bile acid dependent or bile acid independent bile flow. Hamsters fed butterfat had a higher linkage coefficient
(slope) of cholesterol vs. bile acid output than the safflower oil group (0.023 vs. 0.009, respectively). The linkage coefficient
of phospholipid vs. bile acid output of the butterfat group was higher than the controls (0.278 vs. 0.185, respectively).
In summary, butterfat induced a high cholesterol and phospholipid secretion with a high cholesterol/phospholipid output ratio;
safflower oil induced a high phospholipid secretion with a low cholesterol/phospholipid output ratio. Butterfat and safflower
oil have different effects on biliary lipid secretion. These differences in biliary lipid secretion may explain, in part,
how butterfat and safflower oil differ in affecting gallstone formation in hamsters. 相似文献
12.
We examined the effect of diet on gallstone incidence and the composition of biliary phosphatidylcholines in methyltestosterone-treated
female hamsters. These hamsters were fed a nutritionally adequate purified lithogenic diet containing 2% corn oil, 4% butterfat,
0.3% cholesterol, and 0.05% methyltestosterone, resulting in a cholesterol gallstone incidence of 86%. This incidence was
lowered when mono-and polyunsaturated fats or fatty acids were added to the diet: 2.5% oleic acid resulted in total prevention
of cholesterol cholelithiasis, 2.5% linoleic acid, and 4% safflower oil (78% linoleic acid content) reduced gallstone incidence
to 26 and 8%, respectively. An additional 4% butterfat (29% oleic acid content) produced gallstones in 50% of the animals.
At the end of the 6-wk feeding period, the bile of all hamsters was supersaturated with cholesterol. The major biliary phosphatidylcholine
species in all groups were (sn-1-sn-2): 16:0–18:2, 16:0–18:1, 18:0–18:2, 16:0–20:4, and 18:2–18:2. The safflower oil-and linoleic acidfed hamsters exhibited
an enrichment of 16:0–18:2 (16–18%); added butterfat or oleic acid increased the proportion of 16:0–18:1 (9 and 25%, respectively).
We conclude that the phosphatidylcholine molecular species in female hamster bile can be altered by dietary fats/fatty acids
and that mono-and polyunsaturated fatty acids play a role in suppressing the induced cholelithiasis. 相似文献
13.
Bertram I. Cohen Anil K. Singhal Richard J. Stenger Patricia May-Donath Judith Finver-Sadowsky Charles K. McSherry Erwin H. Mosbach 《Lipids》1984,19(7):515-521
The effects of 2 bile acid analogs, chenodeoxy-oxazoline [2-(3α,7α-dihydroxy-24-nor-5β-cholanyl)-4,4-dimethyl-2-oxazoline]
and ursodeoxy-oxazoline [2-(3α, 7β-dihydroxy-24-nor-5β-cholanyl)-4,4-dimethyl-2-oxazoline] were examined in the prairie dog
model of cholesterol cholelithiasis. Gallstones and biliary cholesterol crystals were induced in 5 out of 6 male prairie dogs
fed a semisynthetic diet containing 0.4% cholesterol for 8 weeks. Six animals maintained on a low cholesterol control diet
(0.08% cholesterol) exhibited neither gallstones nor biliary cholesterol crystals. The addition of 0.06% chenodeoxy-oxazoline
to the lithogenic diet did not prevent induced cholelithiasis or the appearance of cholesterol crystals in bile. In contrast,
0.06% dietary ursodeoxy-oxazoline prevented gallstones in 5 out of 6 prairie dogs (but cholesterol crystals were present in
the bile of 4 of these animals). Histologically, most of the livers from the prairie dogs fed the cholesterol-supplemented
semisynthetic diet showed bile duct proliferation, inflammatory infiltration and fibrosis along the portal tracts. These pathologic
changes were generally not ameliorated by adding chenodeoxy-oxazoline or chenodeoxy-oxazoline plus chenodeoxycholic acid to
the diet. Portal tract pathology was markedly reduced in most animals by adding ursodeoxy-oxazoline to the cholesterol-supplemented
diet. The pathologic changes overall could best be correlated with the presence of gallstones, but not with the incidence
of biliary cholesterol crystals. 相似文献
14.
In the prairie dog model of cholesterol cholelithiasis, a high incidence of gallstones is achieved by feeding a semipurified
lithogenic diet containing 0.4% cholesterol for 2 mo. On occasion, we noted a decrease in the percentage of animals with gallstones
from 90–100% to 50–55%. To explain this phenomenon, we studied the effect of dietary history on gallstone formation. After
weaning, animals were fed either rodent chow or alfalfa plus corn (mo 0–3) followed by a cross-over experiment at mo 4–6.
Gallstone formation then was studied by feeding the lithogenic diet from mo 7 to 8. At sacrifice, the incidences of gallstones,
biliary lipids and tissue cholesterol levels were correlated with dietary history. The incidence of gallstones was 100% only
in animals fed the alfalfa-corn diet from weaning to 3 mo. In addition, the feeding of the alfalfa-corn diet at mo 4–6 increased
gallstone incidence from 65% to 86%. The lithogenic index of all groups was highest when the animals received only alfalfa-corn
prior to the lithogenic stimulus. The activity of hepatic HMG-CoA reductase was elevated in animals fed alfalfa-corn from
weaning to 8 mo, suggesting that this diet stimulates hepatic cholesterol synthesis, leading to increased biliary cholesterol
secretion. It is concluded that previous nutritional conditioning affects the incidence of gallstones. The prairie dog is
a useful model of cholesterol cholelithiasis, but the dietary history of the animals plays an important role in lithogenesis. 相似文献
15.
Irina Kube Manuela Kowalczyk Ute Hofmann Ahmed Ghallab Jan Georg Hengstler Dagmar Führer Denise Zwanziger 《International journal of molecular sciences》2022,23(20)
Women are more prone to develop either hypothyroidism or cholesterol gallstones than men. However, a male predominance in cholesterol gallstones under hypothyroidism was reported. Recently, a novel pathogenic link between thyroid hormone (TH) deficiency and cholesterol gallstones has been described in male mice. Here, we investigate if TH deficiency impacts cholesterol gallstone formation in females by the same mechanism. Three-month-old C57BL/6J mice were randomly divided into a control, a TH deficient, a lithogenic, and a lithogenic + TH deficient group and diet-treated for two, four, and six weeks. Gallstone prevalence, liver function tests, bile composition, hepatic gene expression, and gallbladder aquaporin expression and localization were investigated. Cholesterol gallstones were observed in lithogenic + TH deficient but not lithogenic only female mice. Diminished hydrophilicity of primary bile acids due to decreased gene expression of hepatic detoxification phase II enzymes was observed. A sex-specific expression and localization of hepatobiliary aquaporins involved in transcellular water and glycerol permeability was observed under TH deficient and lithogenic conditions. TH deficiency promotes cholesterol gallstone formation in female C57BL/6J mice by the same mechanism as observed in males. However, cholesterol gallstone prevalence was lower in female than male C57BL/6J mice. Interestingly, the sex-specific expression and localization of hepatobiliary aquaporins could protect female C57BL/6J mice to cholestasis and could reduce biliary water transport in male C57BL/6J mice possibly contributing to the sex-dependent cholesterol gallstone prevalence under TH deficiency. 相似文献
16.
Bertram I. Cohen Erwin H. Mosbach Charles K. McSherry Beverly Rzigalinski Syoji Kuroki 《Lipids》1986,21(9):575-579
Gallstone formation and dissolution were studied in a prairie dog model of cholesterol (CH) cholelithiasis. Gallstones were
induced in 49 prairie dogs by feeding 1.2% CH in a nutritionally adequate semisynthetic diet for 6 wk (period 1). At 6 wk,
gallstones had developed in all animals examined. The diets were modified by reducing the amounts of CH to 0.4, 0.2, 0.1 and
0.0% (diets 1–4); hyodeoxycholic acid (HDA; 30 mg/kg/day) was added to these diets (diets 5–8). All animals were fed the modified
experimental diets for an additional 8 wk (period 2). At week 14, spontaneous gallstone dissolution had not occurred, even
in the groups given no added dietary CH during period 2 (group 4). Addition of HDA to the diet tended to reduce the incidence
of biliary CH crystals and the size and number of CH gallstones. Biliary CH remained elevated and the lithogenic indices in
all groups were found to be greater than 1.0 at the end of the experiment. Liver and plasma CH levels tended to be lower in
the groups fed HDA. In these groups, HDA and 6βHDA became the major biliary bile acids. This study demonstrates that HDA achieved
partial dissolution of gallstones in bile supersaturated with CH. 相似文献
17.
Bertram I. Cohen Takahiro Mikami Nariman Ayyad Akira Ohshima R. Infante Erwin H. Mosbach 《Lipids》1995,30(9):855-861
The effects of β-muricholic acid and hyocholic acid on cholesterol cholelithiasis were examined in two animal models. The
following experiments were carried out: A) In a gallstone prevention study, prairie dogs were fed the lithogenic diet with
or without 0.1% β-muricholic or 0.1% hyocholic acid for eight weeks. B) In a second prevention study, hamsters were fed the
lithogenic diet with or without 0.1% β-muricholic acid or 0.1% hyocholic acid for six weeks. C) In a gallstone dissolution
study, hamsters were fed the lithogenic diet for six weeks to induce stones; stone dissolution was examined during administration
of a cholesterol-free purified diet with or without 0.1% β-muricholic acid or 0.1% hyocholic acid. In the prevention study
in prairie dogs (A), both bile acids failed to prevent stone formation, the cholesterol saturation index of bile was 0.89
in the lithogenic controls, remained unchanged with hyocholic acid and increased to 1.52 in the β-muricholic acid group. In
the prevention study in hamsters (B), β-muricholic acid completely inhibited the cholesterol cholelithiasis (0% stone incidence);
the cholesterol saturation index of bile was 1.78 (compared to lithogenic controls, 1.37). Hyocholic acid reduced stone incidence
to 16% with a cholesterol saturation index of 0.98. In the dissolution study in hamsters (C), preexisting cholesterol gallstones
were not dissolved by either hydrophilic bile acid after feeding these bile acids for an additional six weeks; at the end
of the experiment, the cholesterol saturation indices were below unity. These studies suggest that, in the hamster animal
model, hydrophilic bile acids may be useful for the prevention of gallstones but not dissolution of preestablished cholesterol
gallstones. 相似文献
18.
In an attempt to combine the hypocholesterolemic properties of plant sterols with the hypotriglyceridemic action of fish oil
FA, plant sterols have recently been esterified to fish oil n−3 PUFA. The objective of this study was to determine the effects
of plant sterols esterified to n−3 PUFA on plasma lipid levels and erythrocyte fragility. For 5 wk, male Golden Syrian hamsters
were fed diets varying in cholesterol and plant sterol content: (i) Noncholesterol (semipurified diet with no added cholesterol
or plant sterols) (ii), Cholesterol (0.25% cholesterol) (iii), Sterols (0.25% cholesterol plus 1% nonesterified plant sterols),
or (iv) Fish oil esters of plant sterols (0.25% cholesterol plus 1.76% EPA and DHA sterol esters, providing 1% plant sterols).
The addition of fish oil esters of plant sterols to the cholesterol diet decreased (P=0.001) plasma total cholesterol levels by 20%, but nonesterified plant sterols did not have such a beneficial impact. In
addition, non-HDL cholesterol concentrations were 29% lower in hamsters fed fish oil esters of plant sterols than in hamsters
fed nonesterified plant sterols (P<0.0001). Despite higher (P<0.0001) plant sterol levels in whole erythrocytes of hamsters fed nonesterified plant sterols and fish oil esters of plant
sterols compared with hamsters fed no plant sterols, no difference was observed in erythrocyte fragility. The present results
show that EPA and DHA esters of plant sterols have a hypocholesterolemic effect in hamsters, and that these new esters of
plant sterols exert no detrimental effect on erythrocyte fragility. 相似文献
19.
Klyohisa Uchida Takashi Aklyoshi Hirotsune Igimi Haruto Takase Yasuharu Nomura Shouichi Ishihara 《Lipids》1991,26(7):526-530
The preventive effect of 3α,7β,12α-trihydroxy-5β-cholanoic acid (ursocholic acid) and ursodeoxycholic acid on the formation
of biliary cholesterol crystals was studied in mice. Cholesterol crystals developed with 80% incidence after feeding for five
weeks a lithogenic diet containing 0.5% cholesterol and 0.25% sodium cholate. When 0.25% ursocholic acid or ursodeoxycholic
acid was added to the lithogenic diet, the incidence as well as the grade (severity) of the gallstones were reduced. Plasma
and liver cholesterol levels were decreased by ursodeoxycholic acid but not by ursocholic acid. Gallbladder cholesterol and
phospholipid levels were decreased by both bile acids. The biliary bile acid level was decreased by ursocholic acid but not
by ursodeoxycholic acid. After feeding ursocholic acid, its level in the bile was about 25% and the levels of cholic acid
and β-muricholic acid decreased. Fecal sterol excretion was not changed by ursocholic acid, but was increased by ursodeoxycholic
acid. After feeding ursocholic acid, fecal excretion of deoxycholic acid, cholic acid, and ursocholic acid increased. No differences
were found between mice, with or without gallstones, in plasma and liver cholesterol levels, biliary phospholipid and bile
acid levels, fecal sterol and bile acid levels, and biliary and fecal bile acid composition. The results suggest that the
lower incidence of crystal formation after treatment with ursocholic acid is probably by a different mechanism than with ursodeoxycholic
acid. In the mouse model, ursodeoxycholic acid exerts its effect at least partially, by decreasing cholesterol absorption.
Ursocholic acid is well absorbed and excreted into bile and transformed into deoxycholic acid by the intestinal microflora
in mice. 相似文献
20.
A gallstone-inducing diet was utilized to examine the effect of dietary proteins (casein, soybean and cottonseed) on gallstone
formation. Casein produced gallstones in 100% of the animals; however, soybean or cottonseed proteins reduced gallstone incidence
to 32% and 0%, respectively. In an effort to ascertain the mechanisms responsible for gallstone formation, serum cholesterol
and the 3 primary biliary constituents (bile acids, phospholipids and cholesterol) were measured. Casein produced a 4-fold
increase in biliary cholesterol, whereas soybean and cottonseed yielded a 3-and 2-fold increase, respectively, when compared
to a commercial diet (Purina, no. 5001). Serum cholesterol was reduced by substituting dietary vegetable protein for animal
protein. This study suggests that substitution of vegetable for animal protein in the diet can decrease gallstone formation
in hamsters. It is proposed that this reduced gallstone formation is due to the decreased concentrations of biliary cholesterol
induced by dietary modification.
Preliminary reports of portions of this work were presented at the XIIth International Congress of Nutrition and at the 73rd
annual AOCS meeting. Liepa, G., and Mahfouz, S. (1982) J. Am. Oil Chem. Soc. 59, 316A 相似文献