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1.
The relative rates of sterol synthesis in the liver, ileum, and lung of the guinea pig have been studied by measuring the
incorporation by tissue slices of14C-labeled acetate into digitonin-precipitable sterols. The liver showed maximum incorporation of acetate at pH 6.5, the ileum
at pH 7.5, and the lung at pH 6.0. The incorporation of acetate approached the maximum rate at a concentration of 10 mM with
the liver and lung and 5 mM with the ileum. Using these conditions of assay, sterol synthesis was measured in the liver, ileum,
and lung of four groups of guinea pigs killed at 6-hourly intervals. Depending on the time of day, the rate of sterol synthesis
in the ileum was from 6 to 14 times that in the liver, while in the lung the rate was up to 3 times that shown by the liver.
Additional studies showed that all regions of the small intestine synthesized sterol at a higher rate than the liver, with
the highest rate of synthesis occurring in the ileum. The rates observed in the adrenal, testis, muscle, adipose tissue, and
skin indicated that these tissues are not quantitatively important sites of sterol synthesis in the guinea pig. 相似文献
2.
The rate of formation of sterol from squalene in livers from suckling rats was less than one-third that of adults. This difference
was due to a lesser activity of microsomal enzymes in the suckling rat livers, and not to any difference in cytosolic sterol
carrier protein 1. The microsomal enzymes and sterol carrier protein 2 of the cytosol required for the conversion 7-dehydrocholesterol
to cholesterol were both lower in suckling rats compared to adults. Both those activities paralleled the differences in HMG-CoA
reductase activities between suckling and adult rats. Feeding of cholestryamine to adult rats increased the activities of
the microsomal enzymes, sterol carrier protein 1 and sterol carrier protein 2 involved in the conversion of squalene to cholesterol. 相似文献
3.
José Iglesias Dolores Gonzalez-Pacanowska Carmen Marco Eduardo Garcia-Peregrin 《Lipids》1993,28(6):549-553
The purpose of the present study was to investigate the physiological control of the main regulatory enzymes of cholesterol
metabolism in isolated enterocytes obtained from chick duodenum, jejunum and ileum. Cholesterol feeding resulted in an inhibition
of 3-hydroxy-3-methylglutaryl-CoA reductase and mevalonate 5-pyrophosphate decarboxylase, while cholestyramine feeding increased
reductase activity in all the regions studied and decarboxylase activity only in duodenum. Cholesterol feeding markedly increased
acyl-CoA:cholesterol acyltransferase, but the effects of cholestyramine were less clear. The effects on transferase activity
cannot be due to differences in the availability of acyl-CoA as exogenous substrate as no significant differences were found
in acyl-CoA hydrolase activity after any of the dietary treatments. The effects of cholesterol feeding were related to changes
in the cholesterol content of epithelial cells, whereas in the case of cholestyramine this relationship was less apparent. 相似文献
4.
Pregnant rats were randomly allocated to one of 3 experimental dietary groups: Group 1–15.5% butter, 2% cholesterol, 0.78%
sodium cholate purified diet; Group 2-standard rat diet with the addition of 10% lard and 2% cholesterol, and Group 3-standard
rat diet. Plasma and milk cholesterol at 10 days postpartum were significantly elevated in dams fed exogenous cholesterol.
The rat of incorporation of [1-14C] acetate into digitonin-precipitable sterols of mammary tissue slices from dams in Group 1 and Group 2 was eight-fold and
two-fold, respectively, less than controls. Mammary tissue cholesterol was greater in dams fed dietary cholesterol. Thus,
our data, for the first time, demonstrate that cholesterol synthesis in lactating rat mammary tissue is suppressed following
cholesterol feeding. In a second experiment, the rate of incorporation of [1-14C] acetate into digitonin-precipitable sterols in kidney and lung tissue of Group 1 rats was suppressed; however, this response
was not as marked as that observed in lactating mammary tissue. The concentration of cholesterol in kidney and lung was greater
than controls. These results suggest that extrahepatic inhibition of cholesterol synthesis exists in the rat with a concomitant
increase in tissue cholesterol. 相似文献
5.
The effect of feeding cholesterol, taurocholic acid, or cholestyramine to chicks on cholesterolgenesis from [1-14C] acetate in liver and intestine was determined in vitro using tissue slices, and in vivo by i.v. injection of [14C] acetate. The conversion of cholesterol to bile acids in liver in vivo was measured in the same treatments after i.v. injection
of [3H] cholesterol. Hepatic cholesterogenesis in vitro and in vivo was depressed by dietary cholesterol and taurocholate and enhanced
by cholestyramine. Intestinal cholesterogenesis in vivo was depressed only by taurocholate whereas ileal cholesterogenesis
in vitro was reduced by dietary cholesterol. Conversion of cholesterol to bile acids was enhanced by dietary cholesterol and
cholestyramine and depressed by taurocholate. Hepatic cholesterol metabolism in the chick appears to be regulated by mechanisms
similar to those reported for other species. 相似文献
6.
Δ9-tetrahydrocannabinol (THC) and merthiolate have been utilized as lysophospholipid acyltransferase inhibitors in metabolic
studies. However, their effects on acyltransferases other than lysophosphatidylcholine:acyl-CoA acyltransferase (LPCAT) are
not known. We have therefore investigated the effectiveness of THC and merthiolate in inhibiting the acylation of lysophosphatidylcholine,
lysophosphatidylethanolamine, lysophosphatidylserine, lysophosphatidylinositol (LPI) and lysophosphatidic acid (LPA) in guinea
pig liver microsomes using oleoyl-CoA and arachidonoyl-CoA as acyl donors. THC inhibited LPCAT and lysophosphatidylethanolamine:
acyl-CoA acyltransferase (LPEAT) by 40–50%, but had no effect or only slightly increased the activities of the other acyltransferases
when assayed with oleoyl-CoA as the acyl donor. The results obtained with arachidonoyl-CoA were similar to those with oleoyl-CoA,
with the exception of a 40% inhibition of lysophosphatidylserine:acyl-CoA acyltransferase (LPSAT) at concentrations of 50
μM or higher. At similar concentrations, merthiolate was more effective than THC in inhibiting the acyltransferases examined.
Selective effects on the acyltransferases were observed at low concentrations of merthiolate (20 μM or less). Thus, LPCAT
was most susceptible, followed by LPI acyltransferases, LPSAT, LPEAT and lysophosphatidic acid:acyl-CoA acyltransferases (LPAAT).
The presence of LPA did not affect the inhibition of LPCAT by merthiolate. Thus the resilience of LPAAT to merthiolate inhibition
was not due to chelation of the compound by the acidic lysolipid. Thiol reagents includingN-ethylmaleiamide, 5,5′-dithio-bis-nitrobenzoic acid, iodoacetate, β-mercaptoethanol and dithiothreitol had little or no effect on the acyltransferases relative
to equimolar concentrations of merthiolate. The above results indicate that merthiolate is a much more effective inhibitor
of lysophospholipid:acyl-CoA acyltransferases than is THC, and that the selectivity exhibited by merthiolate may be due to
direct and specific interaction with the acyltransferases. 相似文献
7.
We reported earlier on the occurrence of cholinephosphotransferase in the mitochondria of guinea pig lung. In order to determine
whether organ and/or species specificities exist in regard to the cholinephosphotransferase activity in mitochondria, we have
compared the subcellular distribution of the enzyme in the liver and lungs of rats and guinea pigs. Even though the activity
of the enzyme was higher in microsomes than it was in mitochondria, the mitochondrial activity was authentic in both tissues
of both species. The authenticity of mitochondrial activity was established by marker enzyme studies and ultrastructural examination
of mitochondrial preparations.
Presented in part at the Seventy-third Annual Meeting of the Federation of American Societies for Experimental Biology, New
Orleans, LA, March 1989. 相似文献
8.
In guinea pigs, total plasma cholesterol concentrations increased above the control values after single intravenous injections
and after 3 days of continuous subcutaneous administration of neurotensin (NT). A high dose of NT (125 pmol/100 g body weight)
induced tachycardia and severe respiratory distress; the lowest dose (1.25 pmol/100 g body weight) had the greatest hypercholesterolemic
effect 15 min after the injections. The bulk of the total plasma cholesterol was in low density lipoprotein fractions. Cholesterol
increased in the same fractions after intravenous administrations of NT. NT induced a decrease in the cholesterol content
in the ileum but did not affect significantly the cholesterol content in the liver, kidneys or adrenals. In 48-hr fasted controls,
plasma cholesterol concentration and cholesterol content in the liver, kidneys, adrenals and terminal ileum increased; after
intravenous injections of NT, plasma cholesterol concentration further increased but cholesterol content of the liver, kidneys
and ileum decreased. In fed animals, the concentration of the biliary taurochenodeoxycholic acid increased above the control
values 5 and 35 min after the intravenous injections of NT. In fasted controls, the total concentration of bile acids was
higher than in fed controls, but only the concentration of taurochenodeoxycholic acid further increased after the injections
of NT. Proportionately more taurochenodeoxycholic acid than cholesterol was present in bile after the intravenous injections
of NT. These data are consistent with the hypothesis that NT has a regulatory role in intestinal cholesterol transport. 相似文献
9.
Cholesterol fed guinea pigs develop a hemolytic anemia accompanied by high cholesterol concentrations in the liver, plasma,
and red cells. We have studied the bile acid metabolism of guinea pigs fed a diet with or without cholesterol in a search
for the factor(s) which prevent adequate control of their body cholesterol pool and, therefore, its pathological consequences.
The results show that in the cholesterol fed guinea pig the synthesis (and excretion) of bile acids was at least three times
greater than in controls. This is the result of a doubling of the fractional turnover rate and a smaller increase in the pool
size. The major increase of the bile acid pool was in the liver. The main bile acid in gall bladder bile and small intestines
was chenodeoxycholic acid, with smaller amounts of 7-ketolithocholic and ursodeoxycholic acids. In the caecum, large intestines,
and feces, the major bile acid was lithocholic acid. 相似文献
10.
Effect of dietary vitamin E levels on fatty acid profiles and nonenzymatic lipid peroxidation in the guinea pig liver 总被引:1,自引:0,他引:1
G. Barja S. Cadenas C. Rojas R. Pérez-Campo M. López-Torres J. Prat R. Pamplona 《Lipids》1996,31(9):963-970
Guinea pigs were fed for five weeks with three diets containing different levels of vitamin E: LOW (but nondeficient, 15 mg
of vitamin E/kg diet), MEDIUM (150 mg/kg diet), and HIGH (1,500 mg/kg diet). Dietary vitamin E supplementation did not change
oxidative stress indicators in the hydrophilic compartment but increased liver α-tocopherol in a dose-dependent way and strongly
decreased sensitivity to nonenzymaticin vitro liver lipid peroxidation. This last effect was already observed in group MEDIUM, and no further decrease inin vitro lipid peroxidation occurred from group MEDIUM to group HIGH. The protective effect of vitamin E againstin vitro lipid peroxidation was observed even though an optimum dietary concentration of vitamin C for this animal model was present
in the three different vitamin E diets. Both HIGH and LOW vitamin E decreased percentage fatty acid unsaturation in all phospholipid
fractions from membrane origin in relation to group MEDIUM. The results, together with previous information, show that both
vitamin E and vitamin C at intermediate concentrations are needed for optimal protection against lipid peroxidation and loss
of fatty acid unsaturation even in normal nonstressful conditions. These protective concentrations are higher than those needed
to avoid deficiency syndromes. 相似文献
11.
The conversion of squalene to digitonin precipitable sterols by microsomes and soluble fractions from liver and the incorporation of mevalonate into nonsaponifiable lipids and digitonin precipitable sterols by 5000 g liver supernatant was studied in suckling rats and rats weaned on diet (Purina chow) supplemented with varying levels of cholesterol. The results indicate that the conversion of squalene to digitonin precipitable sterols was low in suckling rats and high in rats weaned on Purina chow diet. Weaning rats on 1% cholesterol supplemented diet effectively eliminated the post-weaning increase in mevalonate incorporation into nonsaponifiable and digitonin precipitable sterols, and in the conversion of squalene to digitonin precipitable sterols. The incorporation of mevalonate into nonsaponifiable lipids and digitonin precipitable sterols, and of squalene into digitonin precipitable sterols also was studied in liver preparations from adult rats which were starved and refed control or cholesterol supplemented diet. It was observed that the conversion of squalene to digitonin precipitable sterols by liver fractions from fasted rats was low, while that by liver fractions from rats refed control diet was higher. Furthermore, the post-fasting increase in the conversion of mevalonate to nonsaponifiable lipids and digitonin precipitable sterols and in squalene to digitonin precipitable sterols conversion essentially was eliminated by refeeding a 1% cholesterol supplemented diet. The low conversion of squalene to digitonin precipitable sterols in suckling rats, rats weaned on cholesterol supplemented diet, and adult rats that were starved, or starved and refed cholesterol supplemented diet, was due to the reduced activity of microsomal enzymes. It is concluded from this study that dietary cholesterol prevents the increase in cholesterol synthesis observed in developing and regenerating liver by suppressing the activities of one or more enzymes between mevalonate and squalene and between squalene and cholesterol. 相似文献
12.
Preterm guinea pigs were delivered on day 65 of gestation (term=68 d) and were allowed either free or restricted access to
food for the subsequent 48 h. Plasma phosphatidylcholine (PC) concentration increased postnatally from 190 (range 144–307)
to 751 (426–1039) and 883 (758–977) μM for fed and starved pups, respectively. Plasma PC composition in both groups of pups
was characterized by selective and equivalent relative increases to individual molecular species containing 18∶0 at thesn-1 position. Hepatic PC concentration increased from 6.75 (5.41–8.20) to 8.65 (6.54–10.63) and 9.23 (8.18–10.17) μmol/g for
fed and starved pups, respectively, and, under all conditions, hepatic PC molecular composition closely mirrored that of plasma
PC. These results support the hypothesis that the molecular species composition of plasma PC for the guinea pig in the immediate
postnatal period is determined largely by the composition of the hepatic PC pool destined for lipoprotein secretion. Hepatic
PC composition and concentration of the starved neonatal guinea pig were maintained independently of any dietary nutrient
intake, at the expense of mobilization of extra hepatic lipid reserves. While this adaptive mechanism has inherent limited
survival potential in neonatal starvation, it has implications for studies measuring plasma phospholipid fatty acid compositions
as biochemical markers of dietary fat intake in preterm infants. 相似文献
13.
Rabbits were fed diets enriched with cholestanol or cholestereol (3.5 g/wk) for 4–12 weeks. During cholestanol feeding, the
concentration of cholestanol in blood serum, liver, heart and aorta increased 15–30 times. In serum and liver, the concentration
of cholesterol also increased. Cholestanol-fed rabbits developed inflammatory changes in the liver, with proliferation of
small bile ducts. Liver tests were only slightly abnormal. Morphological atherosclerosis of the aorta was only occasionally
seen in rabbits receiving cholestanol for eight weeks or less.
During cholesterol feeding, the amounts of cholesterol in different tissues increased dramatically, most in the aorta. Morphological
atherosclerosis in the aorta was found in all rabbits fed cholesterol-enriched diets for more than four weeks. Brain cholestanol
was doubled in rabbits fed cholestanol for eight weeks, whereas brain sterols did not change significantly during cholesterol
feeding. After an additional regression period with cholestyramine for eight weeks, the increased content of cholestanol in
the brain was unchanged in cholestanol-fed rabbits. These observations are discussed in relation to the cholestanolosis of
the brain that develops in the rare inherited human disease cerebrotendinous xanthomatosis. 相似文献
14.
The influence of dietary simvastatin, cholestyramine, and the combination of simvastatin plus cholestyramine on hepatic cholesterol
metabolism has been investigated in male rats. Recovery from the effects of the drugs was also investigated by refeeding normal
chow for 24 h. Both drugs, alone and in combination, increased 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase activityin vitro, but activity returned toward control values, after drug withdrawal. Acyl-CoA:cholesterol acyltransferase (ACAT) was significantly
reduced (P<0.001) by simvastatin (−75%), cholestyramine (−71%), and by the drug combination (−81%), due both to a decrease in microsomal
cholesterol and to nonsubstrate-dependent modulation of enzyme activity. Refeeding control diet increased ACAT activity but
not to control levels. The enhanced activity arose partly from higher microsomal cholesterol and partly from increases in
total enzyme activity. Cytosolic neutral cholesteryl ester hydrolase (CEH) activity was substantially elevated by simvastatin
(3-fold) and by the drug combination (6-fold), whereas the effect of cholestyramine was smaller (1.5-fold). Normal chow for
24 h only partially returned cytosolic CEH activity to control values. Microsomal CEH activity was increased by simvastatin,
alone and in combination with cholestyramine (1.4 to 1.7-fold), and was also enhanced, in the cholestyramine-treated animals,
following drug withdrawal. Removal of simvastatin did not allow recovery of this enzyme activity, while withdrawal of the
drug combination led to values 29% below controls. The results indicate that in the rat, simvastatin and cholestyramine alter
both ACAT and CEH activity, as well as inhibiting HMG-CoA reductase activity. 相似文献
15.
Effects of ketoconazole on cholesterol synthesis and precursor concentrations in the rat liver 总被引:1,自引:0,他引:1
Ketoconazole, an antimycotic agent, given to rats for a week as 0.05% food addition had no effect on the hepatic concentrations
of free and esterified cholesterol or on the activity of acyl coenzyme A: cholesterol-acyltransferase (ACAT). However, the
levels of free methylated cholesterol precursors, especially lanosterols, less markedly Δ8,24 and Δ8-dimethyl sterols and monomethyl sterols, were increased after only one day's treatment, while those of esterified methyl
sterols were increased inconsistently, and those of free and esterified Δ8-lathosterol, lathosterol and desmosterol were not affected at all. Cholestyramine treatment had no significant effect on
ACAT in spite of a decrease in the hepatic content of esterified cholesterol and caused a marked increase in the free cholesterol
precursor levels, especially in those of lathosterols. Cholestyramine given to ketoconazole-treated rats increased the hepatic
levels of Δ8 and Δ7-lathosterols but not desmosterol or methylated cholesterol precursors. Ketoconazole increased and cholestyramine markedly
decreased plantssterols, sitosterol and campesterol in the liver. In serum, the contents of both lanosterols and lathosterol
were increased but that of cholesterol tended to be decreased by ketoconazole (−19%). The results indicate that ketoconazole
impairs demethylation processes at C-14 and to some extent at C-4 in the rat liver, resulting in lowered serum cholesterol
level. 相似文献
16.
Binding properties of liver cytosolic protein for oleic acid, palmitoyl-CoA and bromosulphophthalein (BSP) were compared for
rat, mouse and guinea pig. Hepatic cytosol of rat, mouse and guinea pig contained proteins with a molecular weight of ca.
12,000 and had an affinity for [1-14C]-oleic acid. The concentration of fatty acid-binding protein (FABP) was almost the same in livers of the animals of the
3 species and was ca. 50 μg/mg cytosolic protein. Electrophoretic studies revealed that FABP from hepatic cytosol of rat,
mouse and guinea pig, purified with affinity chromatography, are distinct from one another in terms of their charge. FABP
of rat liver was capable of binding any 3 ligands-oleic acid, palmitoyl-CoA and BSP—at relatively high binding capacity. FABP
of mouse liver also bound oleic acid and palmitoyl-CoA to a great extent, but its binding capacity for BSP was only one-third
that of rat liver. FABP of guinea pig liver bound less oleic acid and palmitoyl-CoA than rat liver, whereas it had almost
the same binding capacity for BSP as rat liver. 相似文献
17.
18.
Soy sterols increased the incorporation of acetate into cholesterol by rat liver slices and prevented the depression of cholesterogenesis
caused by dietary cholesterol. Acetate incorporation into cholesterol by intestinal slices was not affected by soy sterols
but was decreased by cholesterol. The results with liver slices agree with the view that soy sterols, by interfering with
the intestinal absorption of cholesterol, prevent the feedback inhibition of hepatic cholesterogenesis. 相似文献
19.
Hepatic and serum phytosterol concentrations were compared in the rat under basal conditions and during activated cholesterol
and bile acid production due to squalene and cholestyramine feeding. Both treatments consistently decreased hepatic and serum
levels of sitosterol and campesterol and, unlike esterified cholesterol, esterified plant sterols were not increased in liver
during squalene feeding. Serum levels of phytosterols were decreased quite proportionately to those in the liver. The hepatic
levels of sitosterol and campesterol closely correlated with each other, but not with cholesterol levels. The percentage esterification
of both phytosterols was lower than that of cholesterol. The results indicate that activation of hepatic sterol production
leads to depletion of hepatic plant sterols. It is suggested that poor esterification of plant sterols may contribute to this
decrease. 相似文献
20.
Effect of sitosterol on the rate-limiting enzymes in cholesterol synthesis and degradation 总被引:4,自引:0,他引:4
Attempts were made to develop an animal model for phytosterolemia. Infusion of Intralipid containing 0.2% sitosterol in rats
gave circulating levels of sitosterol of about 2.5 mmol/l, which is similar to or higher than those present in patients with
untreated phytosterolemia. In addition, the infusions gave serum levels of cholesterol nearly twice those obtained in rats
infused with Intralipid alone or Intralipid containing 0.2% cholesterol. The hepatic HMG-CoA reductase activity was unaffected
or slightly increased by the sitosterol infusions (not statistically significant). The cholesterol 7α-hydroxylase activity
was slightly depressed (ca. 30%). In the case of 7α-hydroxylation of endogenous cholesterol, the depression reached statistical
significance (p<0.05). The microsomal content of sitosterol in the sitosterol-infused rats was about 30% of that of microsomal
cholesterol. The effect of sitosterol on 7α-hydroxylation of cholesterol was investigated by incubations of acetone powder
of rat liver microsomes with mixtures of cholesterol and sitosterol. Sitosterol mixed with cholesterol to a composition similar
to that found in the above microsomal fraction had a depressing effect on 7α-hydroxylation of cholesterol. This degree of
depression was of the same magnitude as that found in the sitosterol infusion experiments. The possibility is discussed that
the hypercholesterolemia obtained in the β-sitosterol-infused rats is due to the inhibitory effect of sitosterol on the cholesterol
7α-hydroxylase. 相似文献