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1.
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
2.
This study was designed to elucidate the effect of the synthetic androgen, methyltestosterone, on bile flow and biliary lipid
secretion in female hamsters. Animals were divided into four groups and fed the following diets: group 1, lithogenic diet
for three weeks; group 2, lithogenic diet+0.05% methyltestosterone for three weeks; group 3, lithogenic diet for six weeks;
group 4, lithogenic diet+0.05% methyltestosterone for six weeks. At the end of each experimental period, the hamsters were
operated on to establish external biliary fistulas. During the depletion of the endogenous bile acid pool (for two hours),
the basal bile flow of group 4 was significantly smaller than that of group 3. Basal bile acid output was significantly lower
in the methyltestosterone-fed groups 2 and 4 than in control groups 1 and 3. In contrast, groups 2 and 4 secreted more cholesterol
than groups 1 and 3. Group 4 had a higher ratio of cholesterol output to phospholipid output than group 3. Increasing doses
of taurocholate were infused after the bile acid depletion period, and it was found that methyltestosterone did not change
the bile acid independent bile flow. The increments in cholesterol or phospholipid output induced per increments of bile acid
output (linkage coefficients) were analyzed by linear regression. The methyltestosterone-fed groups (groups 2 and 4) had a
higher linkage coefficient of cholesterol output to bile acid output than the control groups (groups 1 and 3). The linkage
coefficients of phospholipid output to bile acid output of groups 2 and 4 were also higher compared to groups 1 and 3. The
linkage coefficient of cholesterol output to phospholipid output of group 2 was higher than that of group 1. These results
suggest that methyl-testosterone stimulated the cosecretion mechanism of cholesterol and phospholipid in bile associated with
an increasing ratio of cholesterol to phospholipid. In conclusion, the synthetic androgen, methyltestosterone, caused a decrease
in basal bile flow and bile acid secretion, and an increase in basal cholesterol secretion and the biliary cholesterol-to-phospholipid
ratio. These findings explain, in part, how methyltestosterone intensifies the formation of cholesterol gallstones in female
hamsters. 相似文献
3.
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
4.
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
5.
In the rat, both fish oil diet and thyroid hormone replacement are reported to augment bile cholesterol secretion out of proportion
to bile flow or secretion of other bile lipids. We sought common mechanisms for these effects and evaluated the role of phospholipid
fatty acid composition in the process. Methimazole-treated hypothyroid rats were fed low-fat chow or chow supplemented with
10% corn oil or fish oil, and were studied before and after thyroid hormone treatment. Serum, hepatic, and bile lipids were
measured, phospholipid fatty acid composition determined, and hepatic 3-hydroxy-3-methylglutaryl CoA reductase activity assayed.
Fish oil diet stimulated cholesterol secretion into bile only after thyroid hormone was given, and this action was synergistic
with that of thyroid hormone. Reduced serum cholesterol in fish oil-treated rats was associated with increased biliary cholesterol
secretion and diminished hepatic cholesterol content. This suggests that augmented biliary cholesterol secretion may contribute
to the fish oil-induced reduction of serum cholesterol. No definite relationship between hepatic or biliary phospholipid fatty
acid composition and biliary secretion was apparent, although high bile cholesterol secretion was associated with a low percentage
of hepatic and bile phospholipid linoleic acid. 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.
Vitamin E inhibits fish oil-induced hyperlipidemia and tissue lipid peroxidation in hamsters 总被引:1,自引:0,他引:1
Stan Kubow Nathalie Goyette Selim Kermasha Jean Stewart-Phillip Kristine G. Koski 《Lipids》1996,31(8):839-847
Previous research has linked hyperlipidemia with increased serum concentrations of lipid peroxidation products; however, a
specific association between diet-induced oxidative stress and hyperlipidemia has not been studied. In the present study,
the relationship between tissue lipid peroxidation and hyperlipidemia induced by ingestion of fish oil was examined. In Experiment
1, male Golden Syrian hamsters were fed semipurified diets composed of 1.6 wt% safflower oil plus 15.0 wt% of either butterfat
(BF), safflower oil (SAFF), or high-cholesterol menhaden oil [MHO(H-CHOL)] semipurified diets for 27 d. The cholesterol contents
of the diets were adjusted to 0.088%. The MHO(H-CHOL)-fed hamsters exhibited higher serum concentrations of total cholesterol,
triglycerides, apolipoprotein B, and lipid peroxides when compared to the BF and SAFF diet groups. In a further study (Experiment
2), hamsters were fed for 27 d three dietary treatments: (i) MHO(H-CHOL) with no vitamin E content; (ii) a low-cholesterol
menhaden oil containing high concentrations of vitamin E (2.5 mg tocopherol/g oil or dietary concentrations of 375 mg/kg)
[MHO(L-CHOL)+E]; and (iii) the MHO(L-CHOL+E) with added cholesterol (595 mg/kg) [MHO(L-CHOL)+CHOL+E] to match the cholesterol
content of the MHO(H-CHOL). The MHO(L-CHOL)+E and MHO(L-CHOL)+CHOL+E diet groups showed lower concentrations of serum cholesterol,
triglycerides, and hepatic lipid peroxides than the MHO(H-CHOL)-treated group. Moreover, in contrast to the hypercholesterolemia
caused by the MHO(H-CHOL) feeding, the MHO(L-CHOL)+E and MHO(L-CHOL)+CHOL+ E diets did not show a serum cholesterol-elevating
action. This study supports the hypothesis that oxidative stress in the Syrian hamster could play a causal role in dietary-induced
hyperlipidemia which can be inhibited by high vitamin E intake. 相似文献
8.
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
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.
Marie-Laure Favier Pierre-Etienne Bost Christian Demigné Christian Rémésy 《Lipids》1998,33(8):765-771
A viscous hydrocolloid (guar gum, GG; 2.5% of the diet) or a steroid sequestrant (cholestyramine; 0.5% of the diet) was included
in semipurified diets containing 0.2% cholesterol to compare the cholesterol-lowering effects of each agent in rats. In the
present model, GG significantly lowered plasma cholesterol (−25%), especially in the density <1.040 kg/L fraction, whereas
cholestyramine was less potent. Bile acid fecal excretion significantly increased only in rats fed cholestyramine, similar
to the cecal bile acid pool; the biliary bile acid secretion was accelerated by GG, but not their fecal excretion, whereas
GG effectively enhanced neutral sterol excretion. As a result, the total steroid balance (+13 μmol/d in the control) was shifted
toward negative values in rats fed the GG or cholestyramine diets (−27 or −50 μmol/d, respectively). Both agents induced liver
3-hydroxy-3-methylglutaryl-CoA reductase, but cholestyramine was more potent than GG in this respect. The present data suggest
that, at a relative low dose in the diet, GG may be more effective than cholestyramine in lowering plasma cholesterol by impairing
cholesterol absorption and by accelerating the small intestine/liver cycling of bile acids, which is interestingly, accompanied
by reduction of bile acid concentration in the large intestine. 相似文献
11.
The present study was undertaken in order to reexamine the effect of n−3 polyunsaturated fatty acid (PUFA)-rich diet supplementation
on lipid peroxidation and vitamin E status of rat organs. Male Wistar rats were fed a diet containing safflower or fish oil
at 50 g/kg diet and an equal amount of vitamin E at 59 mg/kg diet (1.18 g/kg oil; and 1.5 g/kg PUFA in safflower oil diet,
and 4.3 g/kg PUFA in fish oil diet) for 6 wk. Fatty acid composition of total lipids of brain, liver, heart, and lung of rats
fed fish oil was rich in n−3 PUFA, whereas that of each organ of rats fed safflower oil was rich in n−6 PUFA. The vitamin
E levels in liver, stomach, and testis of the fish oil diet group were slightly lower than those of the safflower oil diet
group, but the levels in brain, heart, lung, kidney, and spleen were not different between the two diet groups. The levels
of phospholipid hydroperoxides were determined by the high-performance liquid chromatography-chemiluminescence method and
the levels of thiobarbituric acid-reactive substances (TBARS) were determined at pH 3.5 in the presence of butylated hydroxytoluene
with or without EDTA. Levels of phospholipid hydroperoxides and TBARS in the brain, liver, heart, lung, kidney, spleen, stomach
and testis of the fish oil diet group were similar to those of the safflower oil diet group. The results indicate that high
fish oil intake does not induce increased levels of phospholipid hydroperoxides and TBARS in rat organs. 相似文献
12.
Weanling male Wistar rats were fed for five weeks on standard rat chow (23 g fat/kg diet) or one of four synthetic diets with
butterfat, coconut oil, corn oil, or fish oil as the main lipid source (100 g fat/kg diet). In all diets, 10% of the fat was
provided as corn oil to prevent essential fatty acid deficiency. Significant differences were observed in the saturated, monounsaturated,
and polyunsaturated fatty acid composition, and in the ratio of cholesterol to phospholipid, in the hepatocyte membranes.
The fluidity of hepatocyte plasma membranes was assessed using the fluorescence recovery after photobleaching technique and
steady-state fluorescence anisotropy of diphenylhexatriene. No significant differences were found in the fluidity of plasma
membranes between animals on the different fat diets, despite diet-induced changes in their fatty acid composition. However,
the proportion of lipid free to diffuse in the plasma membrane varied with diet, being significantly greater (P<0.05) in animals fed chow (63.7%), coconut oil (61.5%), and butterfat (57.6%) diets than in those fed the corn oil (47.3%)
diet. Animals fed fish oil showed an intermediate (50.0%) proportion of lipid free to diffuse. The data support the hypothesis
that dietary lipids can change both the chemical composition and lateral organization (lipid domain structure) of rat hepatocyte
plasma membranes. 相似文献
13.
Several agents can alter biliary cholesterol secretion, critical for cholesterol excretion and gallstone formation. Although
salicylate effects on bile formation and gallstones have been studied, biliary lipid secretion has not been measured during
oral aspirin treatment. We examined whether oral acetylsalicylic acid affects bile lipid secretion. Three groups of young
rats were fed chow for 3 wk. Two of the groups then received aspirin at either 1.67 or 3.33 g/kg diet for 4 d. Serum, hepatic,
and bile lipids were measured, as were enzymes of cholesterol synthesis and esterification. With oral aspirin, bile cholesterol
secretion increased by 42% and hepatic cholesteryl ester content decreased by 40%. Serum cholesterol and hepatic free cholesterol
did not change. To evaluate mechanisms of the cholesterol hypersecretion, hypothyroid animals fed low-fat or fish oil diets
and repleted with triiodothyronine were also studied. Aspirin stimulated cholesterol secretion to a degree similar to triiodothyronine.
An additive response was seen in fish oilfed rats. Aspirin did not appear to have a primary action on 3-hydroxy-3-methylglutaryl-CoA
reductase or acyl CoA:cholesterol acyltransferase activities, and had no direct effect on esterification of cholesterol by
isolated hepatocytes. Aspirin may directly increase cholesterol transport into bile or have cell membrane effects which alter
cholesterol transport. It remains to be determined whether the observed alterations in bile cholesterol secretion are specific
to the rat or also apply to humans. 相似文献
14.
Nariman Ayyad Bertram I. Cohen Erwin H. Mosbach Shigeo Miki Takahiro Mikami Yasuko Mikami Richard J. Stenger 《Lipids》1993,28(11):981-986
In the present study, we examined the effect of the following factors on a hamster model of cholesterol cholelithiasis: (i)
the source of the golden Syrian hamsters (Sasco, Omaha, NE or Charles River, Wilmington, MA), (ii) the sex of the experimental
animals and (iii) their age (4 wkvs. 8 wk of age). All hamsters were fed a semipurified diet which contained cholesterol (0.3%) and palmitic acid (1.2%). No cholesterol
gallstones formed in any of the female hamsters regardless of age or source. The 4-week-old male hamsters from Sasco had the
greatest incidence of gallstones (93%). The 8-week-old male hamsters tended to have a lower incidence of cholesterol gallstones
than the younger ones, regardless of the commercial supplier (67vs. 93% for Sasco and 27vs. 40% for Charles River). Female hamsters has higher liver and serum cholesterol levels than the male hamsters; Charles River
hamsters had lower serum cholesterol concentrations than the Sasco animals. Total biliary lipid concentrations were highest
in Sasco male hamsters, but biliary cholesterol (mol%) was lower in the males than in the females (4.2–4.5%vs. 6.1–7.1%) regardless of age. The cholesterol saturation indices were higher in the Sasco females than the corresponding males;
these values were lower in the Sasco hamsters than the Charles River animals, regardless of age or sex. The male Sasco hamsters
had a higher total biliary bile acid concentration (98.9 mg/mL) than the Sasco females (58.9 mg/mL) and the Charles River
animals (24.6% mg/mL for males and 38.2 mg/mL for females). The percentage of chenodeoxycholic acid in bile was significantly
lower, and the percentage of cholic acid was higher in all females as compared to males. We conclude that there is a sex,
age and “strain” difference in cholesterol cholelithiasis in hamsters; it is important to consider these factors when working
with the hamster model of gallstone disease. All female hamsters were markedly resistant to the induction of cholesterol gallstone
disease. 相似文献
15.
Ronit Pakula Fred M. Konikoff Moshe Rubin Yehuda Ringel Yochanan Peled Aliza Tietz Tuvia Gilat 《Lipids》1996,31(3):295-303
The role of phospholipids in biliary cholesterol solubilization and crystallization has only recently begun to be appreciated.
Phospholipid vesicles are believed to be the metastable carrier from which cholesterol nucleates. Cholesterol crystallization
is influenced by the phospholipid species in bile. Feeding rats and hamsters with diets enriched in phospholipids or their
precursors, especially ethanolamine, resulted in reduced cholesterol saturation of bile. Although whole phospholipids are
normal dietary constituents, the effects and safety of phospholipid components have not been tested in humans. In the present
study, we have evaluated the effects of a dietary phospholipid mixture, enriched with phosphatidylethanolamine, on human bile
and red blood cell membrane lipid composition. Five ambulatory volunteers having a chronic indwelling T-tube, with an intact
enterohepatic circulation, were investigated. Thirty-six grams of phospholipids (54% phosphatidylethanolamine, 54% linoleyl
acyl chains) were added to their daily diet for fourteen days. Biliary nucleation time, cholesterol carriers, as well as plasma,
red blood cell membrane, and bile lipid compositions, were monitored. Following phospholipid supplementation, the proportion
of linoleyl chains (18:2) in biliary phospholipids increased significantly from 31.1±1.2 to 37.7±5.3%, while that of oleyl
chains (18:1) decreased from 11.4±1.6 to 9.6±1.1%. These changes were accompanied by an increase of linoleate and its metabolite,
arachidonate, in red cell membranes. Phospholipid feeding did not cause any side effects, and no significant changes in biliary
nucleation time, cholesterol, phospholipid, or bile salt concentrations, or in the distribution of cholesterol within micelles
or vesicles. We conclude that phospholipid feeding is safe, and can be effective as a vehicle for lecithin fatty acyl chain
modulation of bile and lipid membranes. These findings may provide a basis for a controlled modulation of biliary phospholipids
to increase cholesterol solubility in bile. 相似文献
16.
Balboa E Morales G Aylwin P Carrasco G Amigo L Castro J Rigotti A Zanlungo S 《Lipids》2012,47(1):13-25
Niemann-Pick C2 protein (NPC2) is a lysosomal soluble protein that is highly expressed in the liver; it binds to cholesterol
and is involved in intracellular cholesterol trafficking, allowing the exit of lysosomal cholesterol obtained via the lipoprotein
endocytic pathway. Thus, this protein may play an important role in controlling hepatic cholesterol transport and metabolism.
The aim of this work was to study the relevance of NPC2 protein expression in hepatic cholesterol metabolism, biliary lipid
secretion and gallstone formation by comparing NPC2 hypomorph [NPC2 (h/h)] and wild-type mice fed control, 2% cholesterol,
and lithogenic diets. NPC2 (h/h) mice exhibited resistance to a diet-induced increase in plasma cholesterol levels. When consuming
the chow diet, we observed increased biliary cholesterol and phospholipid secretions in NPC2 (h/h) mice. When fed the 2% cholesterol
diet, NPC2 (h/h) mice exhibited low and high gallbladder bile cholesterol and phospholipid concentrations, respectively. NPC2
(h/h) mice fed with the lithogenic diet showed reduced biliary cholesterol secretion, gallbladder bile cholesterol saturation,
and cholesterol crystal and gallstone formation. This work indicates that hepatic NPC2 expression is an important factor in
the regulation of diet-derived cholesterol metabolism and disposal as well as in diet-induced cholesterol gallstone formation
in mice. 相似文献
17.
Luíla Ívini Andrade de Castro Rosana Aparecida Manólio Soares Paulo H. N. Saldiva Roseli A. Ferrari Ana M. R. O. Miguel Claudia A. S. Almeida José Alfredo Gomes Arêas 《Lipids》2013,48(6):609-618
Hamsters were fed for 4 weeks on four different diets: control (C) (balanced diet containing 20 % corn oil as the lipid source), hypercholesterolemic (H) (identical to C but containing 12 % coconut oil, 8 % corn oil and 0.1 % cholesterol as the lipid source), amaranth oil (A) (identical to H without corn oil but with amaranth oil), and squalene (S) (identical to H but admixed with squalene in the ratio found in amaranth oil). There were no significant differences in lipid profile, and in the cholesterol excreted in the animals’ feces from amaranth oil (A) and squalene (S) groups. Fecal excretion of bile acids was greater in the amaranth oil (A) and squalene groups (S) as compared to the other groups. The scores of steatosis and parenchymal inflammation observed in the amaranth oil (A) and squalene groups (S) were superior to the ones observed in the other groups. Our findings demonstrated that amaranth oil, and its component squalene, increased the excretion of bile acids but did not have a hypocholesterolemic effect in hamsters fed on a diet containing high amounts of saturated fat and cholesterol. 相似文献
18.
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
19.
20.
In the present study we investigated the effects of dietary fats containing predominantly PUFA, monounsaturated FA (MUFA),
or saturated FA (SFA) on lipid profile and liver cholesterol 7α-hydroxylase (CYP7α1) mRNA expression and bile acid production
in C57BL/6J mice. The animals (n=75) were randomly divided into five groups and fed a basic chow diet (AIN-93G) (BC diet), a chow diet with 1g/100g of cholesterol
(Chol diet), a chow diet with 1g/100g of cholesterol and 14g/100g of safflower oil (Chol+PUFA diet), a chow diet with 1g/100g
of cholesterol and olive oil (Chol+MUFA diet), or a chow diet with 1g/100g of cholesterol and myristic acid (Chol+SFA diet)
for 6 wk. The results showed that the Chol+SFA diet decreased CYP7α1 gene expression and bile acid pool size, resulting in
increased blood and liver cholesterol levels. Addition of PUFA and MUFA to a 1% cholesterol diet increased the bile acid pool
production or bile acid excretion and simultaneously decreased liver cholesterol accumulation despite decreased CYP7α1 mRNA
expression. The results indicate that the decreased bile acid pool size induced by the SFA diet is related to inhibition of
the liver CYP7α1 gene expression, but an increased bile acid pool size and improved cholesterol homeostasis are disassociated
from the liver CYP7α1 gene expression. 相似文献