Biliary Phospholipid Research Articles

Increased biliary cholesterol secretion in alloxan diabetic mice.

Plasma and liver cholesterol levels and biliary cholesterol, phospholipid and bile acid concentrations were examined in normal and alloxan diabetic mice fed ordinary and 0.5 per cent cholesterol diets. The plasma and liver cholesterol levels markedly increased in the diabetic mice, and the cholesterol diet further increased the liver cholesterol level but not that in the plasma. The gallbladder bile weight increased in the diabetic mice, but not after the cholesterol diet. The biliary lipid concentrations markedly increased in the diabetic mice, and the increases of the cholesterol and phospholipids exceeded that of the bile acids, resulting in increases of the cholesterol molar concentration ratio (mole percent) and the lithogenic index. The cholesterol diet increased the biliary cholesterol concentration and slightly the phospholipid, but not the bile acids. Therefore, the cholesterol mole percent and the lithogenic index increased. Among the biliary bile acid composition, cholic and deoxycholic acids increased and beta-muricholic acid decreased in the diabetic mice, whereas the cholesterol diet feeding decreased cholic acid and increased chenodeoxycholic and alpha-muricholic acids. These data suggest that the mechanism of the increase of biliary cholesterol secretion in diabetic mice is different from that after cholesterol diet.

Effect of taurochenodeoxycholate or tauroursodeoxycholate upon biliary output of phospholipids and plasma-membrane enzymes, and the extent of cell damage, in isolated perfused rat livers.

Isolated perfused rat livers were used to study the effects of taurochenodeoxycholate (TCDC) and tauroursodeoxycholate (TUDC) upon some aspects of biliary composition. After depletion of the endogenous bile salt pool of the liver, introduction of either bile salt brought about increases in bile flow, bile salt output and biliary phospholipid output. Taurochenodeoxycholate needed a lower biliary concentration to produce phospholipid output than did tauroursodeoxycholate. TCDC perfusion caused a substantial output of plasma-membrane enzymes (5'-nucleotidase and alkaline phosphodiesterase) into the bile, whereas TUDC caused little output of either enzyme; this may represent a characteristic difference between the effects of the two bile salts on the hepatobiliary system. The results from TUDC perfusion indicate also that much of the output of biliary phospholipid promoted by bile salts, may be independent of the output of plasma-membrane enzymes promoted by bile salts.

Response of Bile Flow, Biliary Lipids and Bile Acid Pool in the Pig to Quantitative Variations in Dietary Fat

Bile flow, biliary lipids and bile acid pool have been studied in growing pigs adapted to a semipurified diet of 2, 10 or 20% lard. After a 5-day period of apparent digestibility measurement, bile secretion was studied in previously fistulated pigs. The apparent digestibility of lard was maintained at a very high level, whatever quantity of lard was ingested. Daily bile acid output was 49% higher with the 10% lard diet than with the 2% lard diet, whereas no further increase was observed with the 20% lard diet. There was a direct relationship between bile acid output and pool size. Biliary phospholipid output increased by 29.0% between 2 and 10% dietary lard and by 69.5% between 10 and 20% lard. The corresponding rise in biliary cholesterol output was + 33% between 2 and 10 or 10 and 20% lard in the diet. A study of biliary kinetics showed that this adaptation of biliary lipid to dietary fat was observed whatever time of the light/dark cycle was considered. These results, together with a recent demonstration of the implication of endogenous phsopholipids in fat digestion, suggested that, in the course of biliary lipid adaptation to dietary fat content, biliary phospholipid could act in synergy with bile salt, resulting in the maintenance of excellent dietary fat digestion.

Monohydroxy bile salt sulfates: Tauro-3β-hydroxy-5-cholenoate-3-sulfate induces intrahepatic cholestasis in rats

The biologic effects of sulfation of tauro-3β-hydroxy-5-cholenoate and of taurolithocholate were compared. Equimolar amounts (100 nmol/min · 100 g body wt) of the following were administered intravenously to male Sprague-Dawley rats over a 180-min period: taurolithocholate, [14C]taurolithocholate-3-sulfate, tauro-3)β3-hydroxy-5-cholenoate, [14C]tauro-3β-hydroxy-5-cholenoate-3-sulfate, its combination with taurocholate, and a saline-albumin solution (control). Sulfation of taurolithocholate and of tauro-3β-hydroxy-5-cholenoate only prevented the cholestatic effect of the former. Bile flow during infusion of [14C]tauro-3β-hydroxy-5-cholenoate-3-sulfate was reduced by 80% at the end of the experiment. A dose-dependent bile flow reduction was demonstrated. Recovery of the administered bile acid was 3% in urine, 13% in serum, 23% in the liver tissue, and 52% in bile, respectively. Excretion of biliary cholesterol and phospholipids was significantly reduced during the first hour of infusion. Coadministration of taurocholate abolished the cholestatic effect and enhanced the renal excretion of the sulfated bile salt. These data suggest that (a) the cholestatic effect of tauro-3β-hydroxy-5-cholenoate-3-sulfate is comparable with or may even exceed the effect of taurolithocholate and (b) although sulfation renders some bile salts more water soluble, it does not prevent the cholestatic effect of all monohydroxy bile salts.

Reversal of progesterone-induced biliary cholesterol output by dietary cholesterol and ethynylestradiol

The significant increment of biliary cholesterol output induced by the subcutaneous injection of 40 mg/kg body wt. of progesterone to male rats was reversed either by feeding a 1% cholesterol diet or by injecting three daily doses of 2 mg/kg ethynylestradiol. These last two experimental manipulations significantly decreased biliary cholesterol saturation from 44 ± 4% (progesterone) to 30 ± 3% (progesterone + 1% cholesterol diet) and 23 ± 0.5% (progesterone + ethynylestradiol) under circumstances of minor changes in the rates of biliary bile salt and phospholipids outputs. The rate of the microsomal acyl-CoA:cholesterol acyltransferase and the concentration of microsomal cholesterol esters significantly increased more than 100% in both cholesterol-fed and estradiol-injected rats. The rate of biliary cholesterol output was reciprocally correlated with both microsomal cholesterol ester concentration of livers ( r = − 0.47, P < 0.01) and the activity of the hepatic acyl-CoA:cholesterol acyltransf erase ( r = −0.58, P < 0.005) in a series of rats injected with progesterone, with progesterone + 1% cholesterol diet and with progesterone + estradiol. No correlation was found between the rate of biliary cholesterol output and the concentration of microsomal free cholesterol. These experiments demonstrate the existence of a close and reciprocal relationship between the rate of biliary cholesterol output and the rate at which the liver esterifies cholesterol.

The effect of progesterone on the regulatory mechanisms of biliary cholesterol secretion in the rat.

We tested the hypothesis that progesterone, an inhibitor of cholesterol esterification in liver microsomes, increases biliary cholesterol output by increasing the availability of cholesterol. Initial bile samples of 20 min were obtained from acute bile fistula rats after seven daily doses of progesterone (5 to 55 mg per kg of body weight). Biliary cholesterol output correlated with the doses of progesterone, r = 0.64 (p less than 0.005). A 100% increment in biliary cholesterol output was obtained with progesterone doses of 30 to 55 mg per kg of body weight. Under these conditions, biliary phospholipid output increased 50% (p less than 0.02), but bile salt output remained normal. The relationship between biliary cholesterol and phospholipids as a function of bile salt output was studied after acute depletion of the bile salt pool. A rectangular hyperbola was the best curve fitting for the experimental data in control and progesterone-injected rats. In the physiological range of bile salt output, between 60 and 120 nmoles per gm per min, progesterone-injected rats secreted 100% more biliary cholesterol than did controls. The calculated theoretical maximal cholesterol and phospholipid outputs were significantly increased in progesterone-injected animals. Serum and hepatic cholesterol pool, free and ester fractions, remained normal. The acyl-CoA: cholesterol acyltransferase reaction was 30% inhibited in hepatic microsomes of progesterone-injected rats, (p less than 0.05). The changes in biliary phospholipids and cholesterol output produced by progesterone were rapidly reversed by either 0.5% cholesterol feeding or 2 mg per kg of body weight ethynyl estradiol injection. These manipulations simultaneously produced a 100% increment in the microsomal acyl-CoA: cholesterol acyltransferase activity (p less than 0.005) and increased 4-fold the concentration of hepatic cholesterol esters. This experimental model suggests a functional interrelationship between biliary cholesterol output and the rate at which the liver esterifies cholesterol.

The possible role of free fatty acids in the pathogenesis of cholesterol gallstones in man

The lipid composition of hepatic and gallbladder bile was examined in 20 patients with cholesterol gallstones and in 20 control subjects. Lipid fractions other than bile salts, phospholipids and cholesterol were found to be present, i.e., sterol esters, non-identified fractions and, above all, free fatty acids. The latter probably originated from biliary phospholipids via activity of phospholipases, present in the gallbladder wall. No significant difference in amount and pattern of free fatty acids and phospholipids was found in hepatic bile between patients with gallstones and controls. On the contrary, we observed relevant differences in the lipid composition of gallbladder bile. In this way, we consider that the bile becomes lithogenic inside the gallbladder as a consequence of release of free fatty acids, particularly if these are constituted by saturated chains. In fact, these can compete with cholesterol in the solubilization in biliary micelles. On the other hand, free fatty acids can be directly toxic for the gallbladder wall and produce a cholecystitis.

Effects of N-(4-methylbenzylthiocarbonyl)-L-phenylalanine (KF 1492), a new hypolipidemic drug, and clofibrate on lipids metabolism.

The effects of N-(4-methylbenzylthiocarbonyl)-L-phenylalanine (KF 1492) on the intestinal lipid absorption, the biliary lipid composition and alpha-glycerophosphate dehydrogenase (GPD) activity have been investigated in rats in comparison with clofibrate. KF 1492 did not have inhibitory activity on intestinal absorption of cholesterol and triglyceride. In the KF 1492-treated group (100 mg/kg, 8 d), an increase of bile flow (25.9%) per g liver was observed. The increase of excretion of bile acids (29.9%), phospholipids (45.2%) and cholesterol (33.4%) due to the increase of bile flow was clearly observed but no significant change in the concentration of each lipid was observed. In clofibrate-treated group, the concentration of bile acids and cholesterol in bile was decreased and output of biliary phospholipids was increased. Approximately 5 to 10 times increase of GPD activity was observed in mitochondrial fraction of the KF 1492- or clofibrate-treated rats (0.25% (w/w) in rat chow, 3 weeks). Thus, the increased degradation and excretion of cholesterol to bile may explain the hypocholesterolemic activity of KF 1492.

Studies on fat digestion, absorption, and transport in the suckling rat. III. Composition of bile and evidence for enterohepatic circulation of bile salts

Biliary secretions from suckling rats (10-15 days old) were characterized: bile flow rate was 197.3 microliters/hr per 100 g; bile salt pool size was 19.0 mumol/100 g; secretion rate was 14.5 mumol/hr per 100 g; synthesis rate was 12.0 mumol/day; and the daily turnover frequency was 18.3. Phospholipid and cholesterol secretion rates were 2.3 mumol/hr per 100 g and 0.17 mumol/hr per 100 g, respectively. The bile salt concentration in portal plasma was 0.17 mumol/ml. The fatty acid composition of biliary phosphatidylcholine and ethanolamine, as well as the stereospecific distribution of fatty acids in the former, were similar to that found in phospholipids from adult rat bile. Compositional analysis of bile acids showed greater than 98% taurine conjugates consisting of approximately 54% cholic acid, 40% beta-muricholic acid, 2% chenodeoxycholic acid, and 1% each of deoxycholic and hyodeoxycholic acids. Through the use of intestinal and liver perfusion experiments, we have obtained evidence for enterohepatic circulation of taurocholate in neonatal rats. The level of bile salts found in intestinal contents (49.5 mumol/g), and the biliary phospholipid concentration (11.8 mM) both exceed adult values (6-10 mumol/g and 6.3 mM, respectively) and may be important for the utilization of the large amount of milk triacylglycerols ingested during the suckling period.

Effect of clinofibrate, a new hypelipidemic agent, on biliary and serum lipids in patients with hyperlipidemia

Clinofibrate was given to 15 patients with hyperlipidemia, for 6–8 weeks at the daily daily dose of 600 mg, and its effect on 3 biliary lipid components (cholesterol, bile acids and phospholipids) and on the lithogenic index was investigated. After clinofibrate treatment, 6 of the patients were given 1.5 g/day clofibrate for 6–8 weeks to compare the effect of clofibrate with that of clinofibrate. The molar percentages of biliary cholesterol and phospholipids to the total. mol number of the 3 biliary lipid components decreased, and that of bile acids increased during clinofibrate administration. In this way, the molar ratio of bile acids to cholesterol increased during the treatment. Neither the lithogenic index calculated by the formula of Admirand and Small nor that of Hegardt, Dam and Holzbach was altered significantly by the treatment. There was no apparent relationship between the effect of the drug on the lithogenic index and any of the factors initial lithogenic index, rate of decrease of serum lipids, or type of hyperlipidemia. Although clofibrate had no significant effect on the maximum solubility of cholesterol in the bile, the molar percentage of biliary cholesterol was elevated and the lithogenic index increased as compared with the control and clinofibrate period. No significant influence on bile acid composition in the bile was observed, with either clinofibrate or clofibrate.

Alteration of cholesterol metabolism and hypocholesterolemic properties of 4-O-methylascochlorin in controlled reverse-phase feeding rats.

Modified fungal product 4-O-methylascochlorin (MAC) is an experimental agent affecting lipid and carbohydrate metabolism in mammals. The hypocholesterolemic properties of MAC were studied using rats fed on a standard laboratory diet. Because of the insolubility in water, reproducibility of the hypocholesterolemic activity had usually been poor for rats fed ad libitum. The difficulty was overcome by controlled reverse-phase feeding; MAC significantly lowered serum total cholesterol (s-TC) in rats only when given by gastric intubation soon after diet intake. MAC increased fecal excretion of neutral and acidic sterols and also increased biliary flow accompanying increments in biliary cholesterol, bile acids and phospholipids. A much larger increase in neutral sterols was characteristic for MAC. However, intestinal absorption of cholesterol and cholic acid was unaffected by MAC. Three mechanisms therefore seemed to be working in hypocholesterolemic activity:(a) withdrawal of hepatic cholesterol into bile, (b) a larger fecal loss of sterols following increment of biliary sterols and (c) enhanced bile acid synthesis compensating the larger fecal loss. A negative sterol balance often leads to an increase in hepatic cholesterogenesis. However, cholesterogenesis, as judged from incorporation of the precursors, was unchanged by MAC.

Simultaneous quantitation of biliary cholesterol, bile acids, and phospholipids (as fatty acids), by gas-liquid chromatography, with campesterol as internal standard.

Journal Article Simultaneous quantitation of biliary cholesterol, bile acids, and phospholipids (as fatty acids), by gas-liquid chromatography, with campesterol as internal standard. Get access R L Yunker, R L Yunker Search for other works by this author on: Oxford Academic Google Scholar A S Hassan, A S Hassan Search for other works by this author on: Oxford Academic Google Scholar M T Subbiah M T Subbiah Search for other works by this author on: Oxford Academic Google Scholar Clinical Chemistry, Volume 27, Issue 10, 1 October 1981, Pages 1779–1780, https://doi.org/10.1093/clinchem/27.10.1779 Published: 01 October 1981

Bile lipid alterations in taurine-depleted monkeys

Newborn cebus and cynomolgus monkeys, differing in their inherent taurine-glycine conjugation of bile acids, were fed taurine-free soy protein infant formula (Isomil) with or without added taurine (500 mg/kg dry diet). After 5 months, monkeys were anesthetized, their enterohepatic circulation interrupted, and their bile pool drained for 4.5 h. Bile acid conjugation, total bile acid pool size, biliary lipid composition, and theoretical maximal cholesterol solubility in bile were determined. Taurine depletion in cebus monkey, an obligate taurine conjugator (97%), did not reduce bile acid conjugation with taurine, or did it alter bile acid pool size, biliary lipid composition, or theoretical maximal cholesterol solubility in bile. Conversely, taurine depletion in cynomolgus, a species normally conjugating with some glycine (15 to 20%), significantly reduced conjugation of taurine with bile acids from 84 to 64%, essentially doubling that of glycine from 16 to 36%. Furthermore, theoretical maximal cholesterol solubility in cynomolgus bile improved significantly as a result of taurine depletion. This improvement was associated with increased percentage distribution of biliary phospholipid from 17 to 33%, in turn reflecting an increase in the taurochenodeoxycholate to taurocholate ratio from 0.7 to 2.9. Concomitant increase in biliary cholesterol concentration associated with increased glycine conjugation precluded any changes in the percent saturation of bile which remained constant at 130% for both dietary groups of cynomolgus. Taurochenodeoxycholate uniquely conserved taurine in the face of body taurine depletion. Taurine availability thus potentially has a substantial influence on bile acid characteristics and cholesterol solubility in a glycine conjugating primate.

Concurrent studies of the flow of digesta in the duodenum and of exocrine pancreatic secretion of calves. 7. Influence of milk substitutes on abomasal lipolysis and biliary secretion.

1. The abomasal hydrolysis of lipids and the flow of endogenous (biliary) lipids was studied in two Friesian calves given four milk-substitute diets, by sampling the duodenal digesta. The diets were: reconstituted, mildly preheated, spray-dried skim-milk powder with (SKF) or without (SK) margarine fat or with 500 g/kg skim-milk powder in diet SKF replaced by soy-beran flour (ASKF) or fish-protein concentrate (BSKF) together with dried whey. The diets were given ad lib. twice daily from 13 to 37 d of age, each diet being given for six consecutive days. Collections of duodenal digesta from the re-entrant cannula situated caudal to the bile duct were made for 12 h after feeding the 6th and 12th meals for each diet. Samples from one collection only were subjected to detailed analysis of the lipid classes. 2. The inclusion of non-milk protein (ASKF and BSKF) not only increased the rate of passage of lipid through the abomasum but also the proportion of the lipid present as triglyceride particularly, in the first 2 h after feeding. 3. In a 12 h period, 2.3-6.3 g 'polar' lipids (mainly biliary phospholipids) were estimated to have been secreted. The rate of flow was high during the first hour after feeding and constant thereafter. The quantity of 'polar' lipid was not related to the type of milk fed or the duodenal flow of lipid. 4. When diet SK was fed, the small amounts of lipid present were extensively hydrolysed so that free fatty acids represented 700 g/kg lipid of dietary origin passing through the duodenum. When margarine fat was included in the diets (SKF, ASKF and BSKF), the free fatty acids represented only 210 g/kg lipid of dietary origin. 5. The quantities of lipid and nitrogen passing through the duodenum were poorly related to the quantities ingested at the beginning of the 12 h experimental period but were closely related to each other.

New concepts of mechanisms of hepatocyte bile formation.

New concepts of mechanisms of hepatocyte bile formation.J L BoyerJ L BoyerPublished Online:01 Apr 1980https://doi.org/10.1152/physrev.1980.60.2.303MoreSectionsPDF (4 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByInborn Errors of Bile Acid MetabolismClinics in Liver DiseaseA novel, protective role of ursodeoxycholate in bile-induced pancreatic ductal injuryMáté Katona, Péter Hegyi, Balázs Kui, Zsolt Balla, Zoltán Rakonczay, Zsolt Rázga, László Tiszlavicz, József Maléth, and Viktória Venglovecz1 February 2016 | American Journal of Physiology-Gastrointestinal and Liver Physiology, Vol. 310, No. 3Bile Salt Transporters: Molecular Characterization, Function, and RegulationMichael Trauner, and James L. Boyer1 April 2003 | Physiological Reviews, Vol. 83, No. 2Effect of Thapsia Essential Oils on Bile Composition in Rats29 September 2008 | Pharmaceutical Biology, Vol. 36, No. 5Membrane heterogeneity in isolated rat hepatocytes and liver plasma membrane subfractions: a comparative study using DPH and its cationic derivative TMA-DPHBiochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1147, No. 2Taurine: An Essential Amino Acid to Prevent Cholestasis in Neonates?28 June 2016 | Annals of Pharmacotherapy, Vol. 26, No. 11The effect of age on the biliary transport maximum (Tm) of bile salts in ratsArchives of Gerontology and Geriatrics, Vol. 14, No. 2Studies on the mechanism of bile salt-independent bile flow impairment in streptozotocin-induced hepatotoxicityToxicology, Vol. 68, No. 3Effects of chlorpromazine on taurocholate transport in isolated rat hepatocytesBiochemical Pharmacology, Vol. 37, No. 21The transport of bile acids in liver cellsBiochimica et Biophysica Acta (BBA) - Reviews on Biomembranes, Vol. 947, No. 1Biliary lipid secretion in the rat. The uncoupling of biliary cholesterol and phospholipid secretion from bile acid secretion by sulfated glycolithocholic acidBiochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, Vol. 922, No. 2Cholestasis and changes in the microcirculation of perfused rat liver caused by the calcium ionophore A23187 and type I antiarrhythmic drugsBiochemical Pharmacology, Vol. 36, No. 18Acute hyperbilirubinaemia in rainbow trout (Salmo gairdneri) caused by resin acidsComparative Biochemistry and Physiology Part C: Comparative Pharmacology, Vol. 88, No. 2Purification and reconstitution of the bile acid transport system from hepatocyte sinusoidal plasma membranesBiochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 862, No. 2Effects of ethinyl estradiol on substrate uptake and efflux by isolated rat hepatocytesBiochemical Pharmacology, Vol. 35, No. 15Bile flow decrease and altered bile composition in streptozotocin-treated ratsBiochemical Pharmacology, Vol. 35, No. 15Effects of iron overload on bile secretion and hepatic porphyrin metabolism in ethinyl extradiol-treated ratsToxicology, Vol. 38, No. 2Biliary excretion of [14C]taurocholate by rainbow trout (Salmo gairdneri) is stimulated at warmer acclimation temperatureComparative Biochemistry and Physiology Part C: Comparative Pharmacology, Vol. 84, No. 1Initial rate of sodium taurocholate uptake in isolated elutriated hepatocytes from untreated and phenobarbital-treated ratsBiochemical Pharmacology, Vol. 34, No. 24Differential distribution of vagal afferent neurons from the rat liverNeuroscience Letters, Vol. 62, No. 2Cholestasis and increased biliary excretion of inulin in rats given 1,1-dichloroethyleneToxicology, Vol. 34, No. 3Transhepatic transport of taurocholic acid in normal and mutant analbuminemic ratsBiochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, Vol. 833, No. 2Origin of biliary phosphatidylcholines studied by coenzyme labelling with [1,1-2H2]ethanolBiochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, Vol. 753, No. 2Bile secretion and liver microsomal mixed function oxidase system in mice with griseofulvin-induced hepatic protoporphyriaToxicology, Vol. 27, No. 1Cholestasis in Infancy2 July 2016 | Clinical Pediatrics, Vol. 22, No. 1Effect of ursodeoxycholate on the bile flow in the ratLife Sciences, Vol. 31, No. 18The effect of α-naphthylisothiocyanate on bile secretion prior to and during the onset of cholestasis in the ratToxicology Letters, Vol. 10, No. 4Hepatic Manifestations of Congenital and Perinatal DiseaseClinics in Perinatology, Vol. 8, No. 3 More from this issue > Volume 60Issue 2April 1980Pages 303-26 Copyright & PermissionsCopyright © 1980 by American Physiological Societyhttps://doi.org/10.1152/physrev.1980.60.2.303PubMed6247725History Published online 1 April 1980 Published in print 1 April 1980 Metrics

Bile formation and biliary lipid composition under the influence of clofibrate and phenobarbital pretreatment in the rat.

The effect of the two enzyme inducing agents, clofibrate and phenobarbital, on bile formation and biliary lipid composition was compared in male rats. Clofibrate (100 mg per kg body weight per day for 14 days) and phenobarbital (at first 60 mg per kg body weight per day for 3 days, then 100 mg per kg body weight per day for 11 days) increase the spontanous bile flow, the 14C-erythritol clearance but do not alter the bile salt excretion, indicating a stimulation of the bile acid independent fraction of bile. The bile of rats pretreated with clofibrate contains less cholesterol than the bile of saline treated control animals, whereas the concentrations of bile acids, phospholipids and cholesterol are reduced in the bile of the rats of the phenobarbital group. Both drugs diminish the cholesterol saturation of bile. If the biliary bile acid concentration and excretion are augmented by an infusion of sodium taurocholate (1000 nmol per min per 100 g body weight), the biliary concentration of cholesterol remains unchanged in the clofibrate group but increases in the phenobarbital group as compared with the saline control animals. The biliary phospholipid concentration is enhanced after clofibrate as well as after phenobarbital pretreatment. These studies indicate that the biliary excretion of cholesterol and phospholipids is at least to some extent regulated by the bile acid excretion. The importance of the synthesis of cholesterol and phospholipids for their biliary excretion, however, seems to be limited: a reduced cholesterol synthesis by clofibrate results in a reduced biliary cholesterol elimination. By contrast, an increased synthesis of cholesterol by phenobarbital and of the phospholipids by both drugs, however, may enlarge the intrahepatic lipid pools and may place more lipids available for biliary secretion.

Digestion and Absorption of Lipids in Chicks Fed Triglycerides or Free Fatty Acids: Synthesis of Monoglycerides in the Intestine

Digestion and absorption of lipids were determined in 3-week-old chicks fed diets containing triglycerides, free fatty acids, or free fatty acids with added glycerol. The 91YCl3 was present as a non-absorbed reference substance. Overall absorption of total fatty acids was highest in triglyceride-fed chicks and lowest in chicks receiving fatty acids. Net secretion of endogenous fatty acids from biliary phospholipids was observed in the duodenum of triglyceride fed chicks, whereas in the other treatments net absorption was observed at this site. Fractionation of the intestinal lipids by thin layer chromatography showed that triglycerides were almost completely hydrolyzed in the duodenum. Monoglycerides were present at high levels in the duodenum of triglyceride fed chicks and at lower levels in chicks receiving free fatty acids and glycerol and at trace levels in free fatty acid-fed chicks. Total micellar fatty acids were lowest in the duodemim of free fatty acid-fed chicks.In vitro incubations of pancreatic homogenate with oleic acid, glycerol, phosphatidyl choline, and taurocholate revealed synthesis of monoglycerides.The poorer fat absorption observed on feeding acidulated soapstock instead of triglycerides is partially explained by less efficient micellarization when free fatty acids are fed.

Chronic administration of chenodeoxycholic acid increases cholesterol saturation in bile in the dog.

Six dogs were given chenodeoxycholic acid, 200 mg/day for 15 days; gallbladder and hepatic bile samples were taken and biliary bile acids, phospholipids and cholesterol were compared to those of fourteen control dogs. It was found that: (1) the cholesterol saturation index of gallbladder bile was higher in treated dogs (0.12 +/- 0.06; m +/- SD) than in controls (0.07 +/- 0.01; P less than 0.05); the proportion of chenodeoxycholic acid in gallbladder bile was higher in treated dogs (27.8 +/- 12.5%) than in controls (4.5 +/- 1.9%; P less than 0.01); (2) in hepatic bile, the saturation index and proportion of chenodeoxycholic acid were significantly higher in treated dogs (respectively 0.13 +/- 0.03 and 21.6 +/- 8.8%) than in control dogs (respectively 0.07 +/- 0.01; P less than 0.01 and 4.6 +/- 2.2%; P less than 0.01). In the dog, chronic administration of chenodeoxycholic acid increases cholesterol saturation in bile. It is concluded that the difference of effect of chenodeoxycholic acid in man and in the dog is not related to the duration of administration, but to a species difference.

Effect of glucagon and insulin upon biliary lipid secretion

The choleretic hormones, glucagon and insulin, were studied to determine whether they influence biliary lipid secretion in the dog. Glucagon was found to decrease biliary cholesterol and phospholipid secretion. These findings provide further support for a canalicular action of glucagon.

The behavior of rat bile phospholipids in the intestine and in incubation media containing pancreatic juice.

Samples of radioactive bile were collected from rats after intravenous injection of potassium soaps ([9-10 3H2] or [1 14C] oleate, [1 14C] linoleate or [9-10 3H2] palmitate). These radioactive acids were chosen because it is well established that, in natural phosphatidyl cholines, palmitic acid is located chiefly at the 1 position and linoleic and oleic acids at the 2 position. After incubation of bile with pancreatic juice, the labeling of unchanged biliary phospholipids was higher when native bile was labeled with oleic acid than with palmitic or linoleic acids. These data suggest that monounsaturated molecular species of biliary phospholipids are more resistant than the diunsaturated ones to in vitro hydrolysis by phospholipase A2. Ninety min after introduction of the radioactive bile into the upper part of the rat duodenum, high labeling of luminal phospholipids was observed regardless of the bile sample used, although labeling of free fatty acids was always low. The passage of intact biliary phospholipids through the intestinal epithelium is discussed.