Yonago Acta medica 2001;44:69–77

Effect of Partial Ileal Bypass on Cholesterol and Bile Acid Metabolism
in Rats
Kiyohisa Uchida*‡, Takashi Satoh†, Yoshio Ogura*, Nobuo Yamaga* and Kazuo
Yamada**Department of Biochemistry, Tottori University Faculty of Medicine, Yonago 683-0826,†Shionogi & Co., Ltd., Osaka 553-0002 and ‡The Cell Science Research Foundation, Osaka
541-0045 Japan
In order to clarify the effect of ileal bypass on cholesterol and bile acid metabolism,
partial (20 cm) ileal bypass rats were fed a 2% cholesterol supplemented diet for aweek after 4 weeks of the operation. The serum and liver cholesterol and phospholipid
levels, biliary cholesterol, phospholipid and bile acid secretions, and fecal cholesterol,
coprostanol and bile acid excretions were examined. The serum cholesterol level in
ileal bypass rats was lower than in normal rats and no hypercholesterolemia was brought
about in ileal bypass rats by feeding them the cholesterol diet. The liver cholesterollevel increased by feeding the cholesterol diet even in ileal bypass rats but the increase
was far less than that in normal rats (22% versus 57%). Biliary bile acid secretion
decreased and fecal bile acid excretion increased markedly in ileal bypass rats.
Deoxycholic acid increased remarkably in both bile and feces and resulted in an increasein the ratio of the sum of bile acids derived from cholic acid over the sum of bile acids
derived from chenodeoxycholic acid (CA/CDCA ratio) in the feces. These results suggestthat the absorption of bile acids is impaired, the pool size of bile acids decreases and thehepatic synthesis of bile acids, especially that of cholic acid, increases in ileal bypass
rats. As a result, cholesterol feeding to ileal bypass rats produces neither hypercholesterolemia nor a further increase in bile acid synthesis.
Key words: biliary lipids; fecal bile acids; fecal sterols; ileal bypass rat; serum and liver lipids

acid pool, is excreted into the feces. In a steadystate, the amounts of bile acids daily excreted
into the feces almost correspond to the amountsof bile acids synthesized daily in the liver.
Bile acids synthesized in the liver are cholicacid and chenodeoxycholic acid in many animal
species including humans. In rats and mice,chenodeoxycholic acid is further converted to
α- and β-muricholic acids in the liver (Botham
and Boyd, 1983; Ogura and Ayaki, 1987). These
primary bile acids are transformed into various
secondary bile acids during enterohepatic circulation (Macdonald et al., 1983; Groh et al.,1993). Cholic acid is transformed into deoxycholic acid and 3α,12α-dihydroxy-7-oxo-5β-Bile acids are synthesized in the liver and secreted into the bile. The bile acids excreted in
the duodenum form micelles with dietary lipids
and enhance intestinal absorption of the lipids.
The bile acids themselves are absorbed by theactive transport mechanism confined to the ileum and by the passive transport mechanism at
any part of the gastrointestinal tract (Dietschy,
1968; Schiff et al., 1972). The bile acids absorbed return to the liver through the portal vein
and are excreted again into the bile, forming theso-called enterohepatic circulation (Carey andDuane, 1994). Most of the bile acids secreted
into the duodenum are absorbed from the intestine, but part of them, less than 5% of the bile

Abbreviations: CA/CDCA ratio, ratio of the sum of bile acids derived from cholic acid over the sum of bile
acids derived from chenodeoxycholic acid; C/P, cholesterol/phospholipid

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K. Uchida et al.

cholanoic acid; chenodeoxycholic acid, intolithocholic acid and 3α-hydroxy-7-oxo-5β-cholanoic acid; and α- and β-muricholic acids, intoω-muricholic acid, hyodeoxycholic acid and
3α-hydroxy-6-oxo-5β-cholanoic acid.
One important biological role of bile acids isto enhance absorption of lipids including cholesterol, but the effect differs with individual
bile acids (Uchida et al., 1980; Reynier et al.,1981). When rats were fed a cholesterol supplemented diet with bile acids, the serum andliver cholesterol levels were markedly increased by a simultaneous feeding of cholic and deoxycholic acids, but not by that of chenodeoxycholic, lithocholic, hyodeoxycholic and ursodeoxycholic acids (Uchida et al., 1980, 1983).
Furthermore, when the effect of bile acids onenhancement of cholesterol absorption was
examined in situ by a rat intestinal loop method,
the cholesterol absorption was greater withtaurocholic acid than with taurochenodeoxycholic acid or taurodeoxycholic acid (about halfof the effect of taurocholic acid), and almost no
effect with tauro-β-muricholic acid or tauroursodeoxycholic acid (Uchida et al., 1990).
The primary bile acids synthesized in theliver are cholic and chenodeoxycholic acids,
but since chenodeoxycholic acid is easily converted to β-muricholic acid in the rat liver, themain bile acids found in rats are cholic acid andβ-muricholic acid, and these two comprise over
80% of the bile acid pool (Uchida et al., 1978).
Cholic acid enhances cholesterol absorption,
while β-muricholic acid does only to a small
degree. Therefore, the composition ratio of
both bile acids (CA/CDCA ratio), is an important factor in cholesterol absorption.
On the other hand, ileal resection or ileal bypass operation is adopted clinically to prevent
obesity or hypercholesterolemia (Buchwald etal., 1974). Since about 60% of the bile acids inthe intestine is absorbed from the ileum during
the enterohepatic circulation of bile acids(Dietschy, 1968; Kanamura, 1982), dysfunctionof the ileum will cause decreases in bile acidabsorption and bile acid pool size, resulting in adecrease in cholesterol absorption. In the present series of experiments, we examined bile
acid metabolism and serum and liver cholester-ol levels in ileal bypass rats kept on an ordinary
diet and a 2% cholesterol supplemented diet.
We adopted a 2% cholesterol concentrationaccording to our previous experiments (Uchia
et al., 1970, 1977).

Materials and Methods

Animal treatments
Wistar strain male rats weighing about 300 g (10–12 weeks old) were kept in an air-conditioned
room (25 ± 1˚C, 50–60% humidity) lighted 12 h
a day (0800–2000) and maintained on a commercial stock diet (Japan CLEA CA-1, Tokyo,
Japan). The cholesterol diet was prepared byadding 2% (w/w) powdered cholesterol to thebasal diet, and fed to rats for a week after 4
weeks of the operation.
The rats were laparotomized along themedian line under sodium pentobarbital anesthesia (50 mg/kg, intraperitoneally) and theintestine was cut at a level of about 20 cm fromthe ileum end. The proximal intestine wasanastomosed to the cecum and the distal end
was closed (Buchwald et al., 1974). A length of
20 cm corresponds to about 1/4 of the intestine(from Treitz’s ligament toward the ileum end).
Rats were individually caged during theperiod of experimentation and 2-day feces
specimens were collected prior to sacrifice as
described previously (Uchida et al., 1977). Five
weeks after the ileal bypass operation, and one
week after beginning of the cholesterol diet, therats were cannulated of their bile ducts with PE10 polyethylene tubings to collect the bile for
30 min under sodium pentobarbital anesthesia(50 mg/kg, intraperitoneally). During the timeof bile collection, the rectal temperature wasmaintained at 36–37˚C using an electric warm
plate. The blood was then withdrawn by heart
puncture and the liver was removed for lipid determination. Bile was collected between 0900
and 1100 to avoid any variation due to the circadian rhythm.

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Ileal bypass on cholesterol and bile acids

room temperature. The extraction procedures
were repeated three times. The combined filtrate was evaporated to dryness under reducedpressure, and the residue was hydrolyzed at
120˚C for 6 h in 1.25 N sodium hydroxide solution. Sterols were extracted with diethylether,
the reaction mixture was acidified with 2 Nhydrochloric acid and then bile acids were extracted with diethylether. The methylated andtrifluoroacetylated bile acids were quantified by
gas-liquid chromatography with a 1% QF-1
column and sterols with a 1% SE-30 column(Uchida et al., 1977; Kinugasa et al., 1981).

Serum and liver lipid determination
The serum was separated by centrifugation at
3000 revolutions per minute for 15 min after
allowing the blood to stand for at least 30 min atroom temperature. A portion of the largest
lobus of the liver (lobus sinistra externa) was
homogenized with 9 volumes of water. The
serum and the liver homogenate were extracted
in 10 volumes of ethanol by refluxing for 20
min at 90–95˚C. Total cholesterol was determined with portions of the serum and liver lipid
extracts as previously reported (Uchida et al.,1965). Phospholipids were determined by themethods of Gomori (1942).

Statistical analysis
Data are expressed as mean ± SE. The difference between the means of variables was calculated by Student’s t-test. Values of P < 0.05
were considered as statistically significant.

Biliary lipid determination
The bile was added to 20 volumes of ethanol,
brought to boil once for several minutes, cooled
down to room temperature, and then filtered.
An aliquot of the filtrate was evaporated to dryness under a stream of nitrogen and the residue
was hydrolyzed at 120˚C for 6 h in 1.25 N
sodium hydroxide solution. Sterols were extracted with diethylether, the reaction mixture
was acidified with 2 N hydrochloric acid andthen the bile acids were extracted with diethylether. The bile acids were methylated withfreshly prepared diazomethane and then trifluoroacetylated with trifluoroacetic anhydride.
The bile acid derivatives were quantified by
gas-liquid chromatography with a 1% QF-1
column and cholesterol with a 1% SE-30
column (Uchida et al., 1970, 1977). Biliary
phospholipids were determined by the methodsof Gomori (1942).
Lithogenic index was calculated by the formula reported by Thomas and Hofmann (1973),
based on the equation of Admirand and Small(1968).

Results
Changes in body weight, liver weight, serum
and liver lipid levels, and diet intake are given
in Table 1. No significant change was found inbody weight, liver weight or diet intake in ileal
bypass rats fed either ordinary diet or the cholesterol diet, compared with normal rats.
The serum cholesterol and phospholipid
levels decreased in ileal bypass rats and did notincrease even while being fed the cholesterol
diet. Therefore, these lipid levels and the cholesterol/phospholipid ratio (C/P ratio) in thecholesterol diet fed ileal bypass rats were lower
than those in the corresponding normal rats.
The liver cholesterol level increased after being
fed the cholesterol diet, but the level in ileal
bypass rats was lower than that in normal rats.
The liver phospholipid levels were almost thesame in all groups.
Data on bile flow, biliary secretions of cholesterol, phospholipid and bile acids, feces dry
weight and fecal excretions of cholesterol, coprostanol and bile acids are given in Table 2.
No change was found in the bile flow and feces
dry weight in ileal bypass rats. A slight decrease in biliary cholesterol secretion was sta-

Fecal sterol and bile acid determination
The feces were dried and powdered, according
to the procedures described previously (Uchida
et al., 1977). An aliquot of the pulverized feces
was extracted with 20 volumes of boiling ethanol for 1 h and filtered after cooling down to71

K. Uchida et al.

Table 1. Effects of ileal bypass on serum and liver lipid levels in rats
Normal rats
Ordinary diet
Cholesterol diet

Ileal bypass rats
Ordinary diet
Cholesterol diet

Number of rats
43
4
3
Body weight(g) 445 ± 15.0
426
± 25.0436± 11.9424± 8.1
Serum cholesterol (mg/dL)
75 ± 0.8
100± 5.4*
60± 3.6*
64± 0.4**
Phospholipids (mg/dL) 137 ± 3.3
133± 11.399± 6.6* 100± 3.1**
C/P ratio
0.55 ± 0.010
0.75 ± 0.023*
0.60 ± 0.020
0.64 ± 0.017**
Liver weight(g)
3.56 ± 0.289
3.81 ± 0.112
3.19 ± 0.113
3.51 ± 0.123
Cholesterol(mg/g)
3.23 ± 0.138
5.08 ± 0.216*
3.26 ± 0.152
3.97 ± 0.216**,***
Phospholipids (mg/g)
41.6 ± 4.02
42.1 ± 1.28
44.7 ± 0.86
44.3 ± 3.10
Diet intake(g/day/rat)
17.5 ± 0.50
17.2 ± 1.09
19.8 ± 1.42
16.8 ± 1.64
Data, mean ± SE.
C/P, cholesterol/phospholipid.
*Statistically significant compared with normal rats on the ordinary diet (P < 0.05).
**Statistically significant compared with normal rats on the cholesterol diet (P < 0.05).
***Statistically significant compared with ileal bypass rats on the ordinary diet (P < 0.05).

tistically significant in ileal bypass rats on theordinary diet but not in those on the cholesterol
diet. However, a marked decrease in biliary
bile acid secretion was found in ileal bypass rats
kept on the ordinary and cholesterol diets. The
decreases attained about 65% and 52%, respectively.
The lithogenic indexes were not affected bycholesterol feeding, but increased slightly in
ileal bypass rats (0.13 ± 0.012% versus 0.20 ±0.018%; combined data in normal and ileal bypass rats in both diet groups).
The fecal excretion of cholesterol, but not of
coprostanol, increased in ileal bypass rats on theordinary diet, but the increase was obscure after

being fed the cholesterol diet. Cholesterol feeding increased the fecal excretion of not onlycholesterol but also coprostanol in both normal
and ileal bypass rats.
The fecal bile acid excretion was markedly
increased in ileal bypass rats. Feeding of thecholesterol diet increased the fecal bile acid excretion in normal rats, but caused no further increase in ileal bypass rats. The level in ileal
bypass rats was almost 4-fold that in normal rats
kept on the ordinary diet, and about twice that innormal rats on the cholesterol diet.
Changes in biliary bile acid composition are
given in Table 3. When normal rats were fed
the cholesterol diet, an increase in chenode-

Table 2. Effects of ileal bypass on biliary and fecal lipid levels in rats
Normal rats
Ordinary diet
Cholesterol diet

Ileal bypass rats
Ordary diet
Cholesterol diet

Bile flow(mL/h/rat)
1.38 ± 0.254
1.88 ± 0.111
1.18 ± 0.074
1.37 ± 0.223
Cholesterol (mg/h/rat)
0.23 ± 0.003
0.24 ± 0.001
0.17 ± 0.016*
0.19 ± 0.034
Phospholipids(mg/h/rat)
8.03 ± 0.854
8.94 ± 0.777
5.96 ± 0.415
7.30 ± 1.240
Bile acids(mg/h/rat) 17.61 ± 4.156
16.95 ± 2.898
6.24 ± 0.618*
7.95 ± 1.490**
Lithogenic index(%)
0.13 ± 0.016
0.13 ± 0.023
0.21 ± 0.022*
0.19 ± 0.035
Feces dry weight (g/d/rat)
4.26 ± 0.201
4.38 ± 0.226
4.99 ± 0.372
4.67 ± 0.597
Cholesterol (mg/d/rat)
2.84 ± 0.303 192.5 ± 11.80*
5.68 ± 0.496* 187.1 ± 43.80***
Coprostanol (mg/d/rat)
3.56 ± 0.456
55.7 ± 1.77*
4.05 ± 0.376
51.7 ± 9.69***
Bile acids(mg/d/rat) 11.46 ± 0.742
24.11 ± 0.803* 45.47 ± 5.904*
45.43 ± 7.359**
Data, mean ± SE.
*Statistically significant compared with normal rats on the ordinary diet (P < 0.05).
**Statistically significant compared with normal rats on the cholesterol diet (P < 0.05).
***Statistically significant compared with ileal bypass rats on the ordinary diet (P < 0.05).

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Ileal bypass on cholesterol and bile acids

Table 3. Effects of ileal bypass on bilary bile acid composition (%) in rats
Normal rats
Ordinary diet
Cholesterol diet

Ileal bypass rats
Ordinary diet
Cholesterol diet

Lithocholic acid
0.4 ± 0.14
1.1 ± 0.22
1.3 ± 0.22*
0.8 ± 0.03
Deoxycholic acid
2.1 ± 0.36
2.9 ± 0.52
33.9 ± 0.88*
22.9 ± 0.20**,***
α-Muricholic acid
3.2 ± 0.93
8.6 ± 2.14
2.9 ± 0.80
4.8 ± 0.38
Chenodeoxycholic acid
3.5 ± 0.74
6.7 ± 0.54*
10.9 ± 2.23*
10.9 ± 2.09
Hyodeoxycholic acid
1.6 ± 0.35
4.9 ± 2.35
1.5 ± 0.47
3.3 ± 1.79
Ursocholic acid10.6 ± 3.87
7.2 ± 0.82
1.6 ± 0.54*
3.2 ± 1.92
Cholic acid +β-Muricholic acid¶
66.0 ± 7.79
51.2 ± 1.91
42.9 ± 3.03*
47.3 ± 0.92
Oxo-bile acids
10.8 ± 3.35
11.2 ± 2.06
2.5 ± 0.29
4.9 ± 2.09**
Others
2.7 ± 0.47
5.7 ± 1.33
2.5 ± 0.37
1.9 ± 0.23
Mean ± SE.
*Statistically significant compared with normal rats on the ordinary diet (P < 0.05).
**Statistically significant compared with normal rats on the cholesterol diet (P < 0.05).
***Statistically significant compared with ileal bypass rats on the ordinary diet (P < 0.05).
¶ Cholic acid and β-muricholic acid were not separable under the present experimental conditions.

oxycholic acid was observed, but no significant
change was detected in the other bile acid fractions. Ileal bypass rats showed a marked increase in deoxycholic acid and chenodeoxycholic acid, and a concomitant decrease in thefraction of cholic acid plus β-muricholic acid,these bile acids were not separable under thepresent experimental conditions. When ileal
bypass rats were fed the cholesterol diet, deoxycholic acid decreased but the level was far higher than the corresponding normal rats.

Changes in fecal bile acid composition are
given in Table 4. Deoxycholic acid markedly
increased, and β- and ω-muricholic acids decreased in ileal bypass rats. Feeding of thecholesterol diet decreased deoxycholic acid in
both normal and ileal bypass rats. The CA/
CDCA ratio increased remarkably in ileal bypass rats, and the ratios decreased after being
fed the cholesterol diet in both rat groups.

Table 4. Effects of ileal bypass on fecal bile acid composition (%) in rats
Normal rats
Ordinary diet
Cholesterol diet

Ileal bypass rats
Ordinary diet
Cholesterol diet

Lithocholic acid
7.6 ± 0.41
6.5 ± 0.48
11.7 ± 2.11*
11.1 ± 1.94**
Deoxycholic acid19.5 ± 1.21
13.3 ± 0.50*
56.5 ± 1.32*
43.0 ± 5.07**,***
α-Muricholic acid
4.1 ± 0.35
5.2 ± 1.24
5.4 ± 1.26
6.6 ± 1.40
Hyodeoxycholic acid
6.5 ± 1.59
10.9 ± 4.30
5.9 ± 1.55
9.8 ± 6.70
β-Muricholic acid¶10.7 ± 3.40
15.6 ± 4.73
3.6 ± 0.82*
4.7 ± 0.61**
ω-Muricholic acid40.6 ± 8.06
36.3 ± 4.87
9.6 ± 2.54*
19.9 ± 4.86**
Oxo-bile acids
2.3 ± 0.23ND
5.4 ± 3.22
ND
Others
7.5 ± 3.92
6.7 ± 2.36
1.8 ± 0.45
4.9 ± 2.20
CA/CDCA ratio
0.37 ± 0.112
0.17 ± 0.013*
1.62 ± 0.25*
0.85 ± 0.20**,***
Mean ± SE.
CA/CDCA ratio, ratio of the sum of bile acids derived from cholic acid over the sum of bile acids derived
from chenodeoxycholic acid; ND, not detectable.
*Statistically significant compared with normal rats on the ordinary diet (P < 0.05).
**Statistically significant compared with normal rats on the cholesterol diet (P < 0.05).
***Statistically significant compared with ileal bypass rats on the ordinary diet (P < 0.05).
¶ This fraction contains a small amount (< 10%) of cholic acid.

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K. Uchida et al.

Fig. 1. Metabolic sequences in the primary and secondary bile acidformation in rats.

The present data demonstrates clearly thatthe biliary secretion of bile acids decreases andthe fecal excretion of bile acids increases in
ileal bypass rats. We found that the hourly
biliary secretion of bile acids decreased to about
35% that of, and the daily fecal excretion of bile
acids increased about 4-fold that of the paired
control rats kept on the ordinary diet. These
data are consistent with our previous experiments on ileal resection rats (Kanamura, 1982).
On the other hand, cholesterol feeding increases biliary and fecal bile acids in rats
(Uchida et al., 1977, 1996). In the present experiments, the increase in biliary bile acid secretion
was obscure, but fecal bile acid excretion increased in normal rats after cholesterol feeding.
However, no further increase in fecal bile acidexcretion was found in ileal bypass rats aftercholesterol feeding. This could be due tohepatic bile acid synthesis having attained amaximal level after ileal bypass and being
unable to respond to further cholesterol feeding.
This supposition, however, is not always consistent with the observations on the bile acidcomposition and the liver cholesterol level.

Discussion
An important step in the enterohepatic circulation of bile acids is the absorption of bile acids
from the distal ileum. The major part of bile
acids is absorbed there by the active transportmechanism (Dietschy, 1968; Schiff et al., 1972),
and the amount comes up to about 60% of thebile acids secreted daily from the liver in rats
(Kanamura, 1982).
Since bile acid synthesis in the liver is regulated by the amount of bile acids returning to
the liver through the portal vein, the synthesisof bile acids increases by ileal resection (Weisand Dietschy, 1974; Kanamura, 1982) or bypass operation (Kobayashi, 1980) or treatmentswith bile acid absorption inhibitors (Gustafsson
et al., 1978). In a steady state, the daily amountof bile acids excreted into the feces is considered to represent the daily amount of bile acids
synthesized in the liver. Therefore, an increasein the synthesis of bile acids is reflected as anincrease in fecal bile acid excretion.
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Ileal bypass on cholesterol and bile acids

Since cholesterol 7α-hydroxylase, the ratelimiting enzyme in bile acid synthesis, is increased by an increment in hepatic cholesterol
concentration through a mechanism involving
nuclear receptors, especially the liver X
receptor (Peet et al., 1998), hepatic bile acidsynthesis, and therefore fecal bile acid excretion, increases during cholesterol feeding(Uchida et al., 1977, 1996). On this occasion,
the synthesis of chenodeoxycholic acid (actually β-muricholic acid in rats) is more enhanced
than that of cholic acid, resulting in a decreasein the CA/CDCA ratio (Uchida et al., 1977,
1996). These changes after cholesterol feeding,an increase in the liver cholesterol level and adecrease in the fecal CA/CDCA ratio, were observed in the present normal rats, and also in theileal bypass rats. These data suggest thatcholesterol feeding affected bile acid synthesis
even in ileal bypass rats, while not changing thetotal amount of bile acids synthesized.
The pool size of bile acids was not detectedin the present experiments, but taking accountof the decrease in the biliary bile acid secretionin the present series of experiments, and ourprevious results on the ileum resected rats

(Kanamura, 1982; Ogura et al., 1993) or others(Weis and Dietschy, 1974), it will be safe to saythat the pool size of bile acids was also decreased in ileal bypass rats. The decrease in thepool size of bile acids, especially that of cholicacid, in ileal bypass rats resulted in a decrease in
the serum cholesterol level, an increase in fecalcholesterol excretion, and no increase in theserum cholesterol level after cholesterol feeding.
The lithogenic index was low in rats and notaffected by cholesterol feeding, but increasedslightly in ileal bypass rats. The present data
are consistent with the report done by KulneffHerlin et al. (1983). The results may support
the concept that ileal resection or bypass increases the risk of cholelithiasis (Bickerstaff
and Moossa, 1983; Pitt et al., 1984).
The composition ratio of deoxycholic acidincreased in ileal bypass rats as shown in the
results. Conjugated cholic acid (mostly taurine
conjugate in rats) is effectively absorbed fromthe distal ileum by the active transport mechanism in normal rats (Dietschy, 1968; Schiff etal., 1972). However, a large amount of conjugated cholic acid enters the colon in ileal bypass
rats and receives modifications such as deconjugation and 7α-dehydroxylation by intestinal
flora (Macdonald et al., 1983; Groh et al.,1993), producing deoxycholic acid. Since apart of the secondary bile acids is also absorbed
from the colon, especially the proximal colon(Schiff et al., 1972), the increase in biliary deoxycholic acid is a result of the copious formation of this bile acid in the colon.
The composition ratios of hyodeoxycholic,β-muricholic and ω-muricholic acids in thefeces showed relatively large variations. Since
β-muricholic acid is considered to be transformed into ω-muricholic acid and then into
hyodeoxycholic acid by intestinal flora (Fig. 1),
the conversion rates differ from individual toindividual according to their intestinal flora.
Therefore, the necessary presentation of theratios of each bile acid in the sum of these threebile acids are calculated and plotted in Fig. 2.
An inverse correlation was observed between
hyodeoxycholic acid and ω-muricholic acid,suggesting that a copious formation of hyode-Fig. 2. Relationship between ω-muricholic acid (ωMCA) and hyodeoxycholic acid (HDCA) formed
from β-muricholic acid in rats.

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K. Uchida et al.

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V, DenBesten L. Ileal resection-induced gallstones: altered bilirubin or cholesterol metabolism? Surgery 1984;96:154–162.
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oxycholic acid resulted in a smaller percentageof ω-muricholic acid, and vice versa.
Coprostanol is also formed from cholesterol
by intestinal flora (Björkem and Gustafsson,
1971; Ren et al., 1996). In normal rats kept onan ordinary diet which contained about 0.1% orless of cholesterol, the amount of coprostanol in
the feces was almost the same as that of cholesterol. After being fed the cholesterol diet, theamount of coprostanol increased about 10-fold,but no significant difference was found between
the normal and ileal bypass rats.

Acknowledgments: We sincerely thank Mr. Haruto
Takase and Mr. Yasuharu Nomura of Shionogi
Research Laboratories for their skillful technicalassistance, Ms. Yoshiko Kurosawa of The Cell Science
Research Foundation, Mr. Morio Oohori of Shionogi
Co. Ltd. and Ms. Yumiko Uyama of the Department ofBiochemistry, Tottori University Faculty of Medicine
for their help in preparing the manuscript.

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or bypass of the distal ileum on the lithogenicity
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Received November 28, 2000; accepted December 27, 2000
Corresponding author: Dr. Kiyohisa Uchida**Present address: The Cell Science Research Foundation, 3-1-8 Dosho-machi, Chuo-ku, Osaka 541-0045 Japan
E-mail: kiyohisa.uchida@shionogi.co.jp

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