Influence of deoxycholic acid on biliary lipids in man.
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Adult↗
Biomedical subjects
B Angelin
Publications and source records attributed to B Angelin.
Postprandial serum bile acids in healthy man. Evidence for differences in absorptive pattern between individual bile acids.
The serum concentrations of cholic acid (C), chenodeoxycholic acid (CD), and deoxycholic acid (D) before and after a standardised meal were determined in five healthy female subjects using a highly specific and accurate gas chromatographic-mass spectrometric technique. The C level rose significantly 60 minutes after the meal, reached a peak after 90 minutes, and had returned to the original level after 150 minutes. In contrast, the serum concentrations of CD and D displayed a significant rise by 30 minutes, reached a peak after 90 minutes, but had not returned to fasting levels after 150 minutes. The serum bile acid responses after a meal suggest that there is considerable absorption of dihydroxy bile acids in the proximal small intestine in man.
Adult↗
Cholesterol and bile acid metabolism in normo- and hyperlipoproteinaemia.
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Bile Acids and Salts↗
Individual bile acids in portal venous and systemic blood serum of fasting man.
The serum concentrations of cholic acid (C), chenodeoxycholic acid (CD), and deoxycholic acid (D) were determined in peripheral venous and portal venous blood from 10 otherwise healthy patients undergoing elective cholecystectomy. A highly specific and accurate gas chromatographic-mass spectrometric technique was used. Peripheral venous serum contained 0.49 +/- 0.16 (mean +/- SEM) mumole per liter of C, 1.55 +/- 0.32 mumoles per liter of CD, and 1.44 +/- 0.57 mumoles per liter of D. Arterial serum, obtained from 5 of the subjects, did not show any differences in bile acid concentrations compared to venous serum. In contrast, the portal venous content of each bile acid was several-fold greater, 6.14 +/- 1.20 mumoles per liter of C, 8.40 +/- 1.84 mumoles per liter of CD, and 6.18 +/- 2.27 mumoles per liter of D. The hepatic uptake of C was estimated to be about 90%, whereas that of CD and D was lower, about 70%. This difference in hepatic uptake between the individual bile acids was reflected in the relative composition of the total bile acids, which was 30:39:31 (C:CD:D) in portal venous serum and 13:50:37 in peripheral serum. Compared to common duct bile obtained simultaneously, the portal vein contained a greater proportion of CD. The relevance of the data obtained to our present concept of the enterohepatic circulation of bile acids is discussed, and it is suggested that the higher fasting level of CD compared to C in peripheral serum results from the combination of a lower fractional hepatic extraction and a higher portal venous input to the systemic circulation.
Aged↗
Effects of cholesterol feeding on synthesis and metabolism of cholesterol and bile acids in germfree rats.
The aim of the present investigation was to study the influence of cholesterol feeding on cholesterol synthesis and fecal excretion of bile acids in germfree rats. Four germfree rats were fed a basal diet containing 0.004% cholesterol and four germfree rats received the same diet supplemented with 0.4% cholesterol for 2 weeks. Cholesterol synthesis was studied by assaying the HMG CoA reductase activity in the liver microsomal fraction. Cholesterol feeding decreased the HMG CoA reductase activity from 28.5 +/- 6.6 (mean +/- SEM) to 9.1 +/- 0.7 pmol/mg protein per min. In another experiment four germfree rats received the basal diet and four germfree rats the cholesterol-enriched diet. After 6 weeks feces were collected in two 4-day pools for analysis of bile acids. The main fecal bile acids were cholic acid and beta-muricholic acid (a metabolite of chenodeoxycholic acid), comprising more than 95% of total bile acids. Cholic acid was increased from 3.9 +/- 0.2 to 9.9 +/- 1.2 mg/kg body weight per day and beta-muricholic acid from 6.6 +/- 0.5 to 21.8 +/- 3.1 mg/kg body weight per day. The percentage of cholic acid decreased from 37.1 +/- 1.1 to 31.2 +/- 1.0%. In conclusion, germfree rats like conventional rats have the ability to compensate for an increased input of dietary cholesterol by inhibition of cholesterol synthesis and stimulation of bile acid synthesis. The synthesis of chenodeoxycholic acid (implied from the fecal excretion of beta-muricholic acid) is stimulated to a greater extent than that of cholic acid.
Animals↗
Elimination of cholesterol in hyperlipoproteinaemia.
1. Cholesterol intake (about 0-25 mmol/day) and the faecal excretion of cholesterol, coprostanol and coprostanone were determined in normolipidaemic control subjects and hyperlipidaemic patients, whose bile acid kinetics had been previously studied. 2. The combined excretion of the neutral steroids (excluding plant sterol and plant sterol metabolites) averaged 1-07 +/- 0-13 (+/-SEM)mmol/day in the control subjects (n=14). The corresponding values in patients with hyperlipoproteinaemia type IIa (n=19), IIb (n=12) and IV (n=23) were 0-86 +/- 0-10, 0-93 +/- 0-11 and 1-48 +/- 0-17 mmol/day respectively. 3. The mean values for the net steroid "balance", defined as the combined amount of bile acid synthesized (determined by an isotope-dilution technique) and the faecal excretion of neutral steroids minus cholesterol intake, were 1-83 +/- 0-22 mmol/day in the control subjects and 1-60 +/- 0-15, 1-81 +/- 0-19 and 3-53 +/- 0-23 mmol/day in patients with type IIa, IIb and IV lipoprotein patterns respectively. 4. No significant correlations between net steroid "balance" and sex, age, serum lipid concentrations, body weight or body surface area were found in any of the groups of subjects. 5. It is concluded that patients with type II hyperlipoproteinaemia eliminate cholesterol as bile acids and neutral faecal steroids normally. The type IV lipoprotein pattern is associated with increased bile acid synthesis and/or elevated faecal excretion of neutral steroids, so that the net steroid "balance" is usually above the normal limit.
Bile Acids and Salts↗
Evidence for the absorption of bile acids in the proximal small intestine of normo- and hyperlipidaemic subjects.
Bile acid composition was determined in duodenal and jejunal aspirates obtained under fasting conditions in normolipidaemic controls and in patients with the type IIa and type IV lipoprotein patterns. In 17 out of the 22 subjects studied, the duodenal as compared with the jejunal aspirates contained proportionally more CD (chenodeoxycholic acid) than C (cholic acid). The two types of aspirates also differed slightly with regard to the D (deoxycholic acid): CD ratio, which was higher in samples drawn from the jejunum. These findings, compatible with an absorpiton of about 30% of CD in the upper small intestine, were approximately the same in all groups of patients. As evidenced by additional experiments in two subjects, an oral intake of cream does not significantly influence the absorption of CD in the upper small intestine.
Bile Acids and Salts↗
The diagnostic value of fasting individual serum bile acids in anicteric alcoholic liver disease: relation to liver morphology.
The aim of the present study was to evaluate the diagnostic value of measuring individual serum bile acids in patients with suspected alcoholic liver disease. A highly accurate and specific mass-fragmentographic technique with high sensitivity was used. Anicteric patients with fatty liver (n = 10) and liver cirrhosis (n = 9) were compared with healthy controls (n = 27). The measurement of serum bile acids did not discriminate patients with fatty liver from controls. In general, an increased serum level of cholic acid indicated more serious liver disease. Determination of chenodeoxycholic acid and deoxycholic acid did not add any further diagnostic information.
Adolescent↗
Portal venous bile acids in cholesterol gallstone disease: effect of treatment with chenodeoxycholic and cholic acids.
We determined the serum concentrations of cholic, chenodeoxycholic and deoxycholic acids in portal and peripheral venous blood in 9 gallstone-free patients and 39 patients with cholesterol gallstones during standardized cholecystectomy. An accurate and specific gas chromatographic-mass spectrometric technique was used. The portal venous concentration of total bile acids was similar in gallstone-free and untreated gallstone patients (n = 20); there was no evidence of a reduced hepatic uptake of bile acids in the latter. Treatment with cholic acid (n = 10) was associated with a 70% increase in cholic acid and normal concentration of total bile acids. In chenodeoxycholic acid-treated patients (n = 9), the portal venous concentration of this bile acid was increased 3-fold; total bile acids were increased about 60%. The estimated hepatic uptake of cholic acid was slightly decreased during chenodeoxycholic acid treatment. The results indicate that neither bile acid inflow to the liver nor hepatic bile acid uptake is reduced in fasting patients with cholesterol gallstones, and treatment with chenodeoxycholic acid increases fasting inflow of bile acids to the liver. The latter may contribute to unsaturation of fasting hepatic bile during treatment with chenodeoxycholic acid.
Adult↗
Sn-protoporphyrin lowers serum bilirubin levels, decreases biliary bilirubin output, enhances biliary heme excretion and potently inhibits hepatic heme oxygenase activity in normal human subjects.
Sn-protoporphyrin, a potent competitive inhibitor of heme oxygenase, the rate-limiting enzyme in the degradation of heme to bile pigment, was administered to 10 normal volunteers: 8 males and 2 females. A significant decrease in the levels of serum (mean decrease; 38%) and biliary bilirubin (mean decrease: 47%) was demonstrated in all 10 subjects. The decrease in these parameters lasted for a minimum of 4 days after administration of the metalloporphyrin. Sn-protoporphyrin also facilitated the excretion of endogenous heme in bile during the 24- to 48-hr period following administration of the compound. The metalloporphyrin was rapidly cleared from plasma with a half-life of 3.4 hr. A small amount (3 to 6%) of Sn-protoporphyrin was excreted in both urine and bile. The activity of microsomal heme oxygenase was measured in five human liver samples freshly obtained at the time of cholecystectomy and varied from approximately 2 to 4 nmoles bilirubin formed per mg protein per hour. The addition of Sn-protoporphyrin to microsomal heme oxygenase isolated from these liver samples resulted in a dose-dependent decrease in the activity of this enzyme at concentrations of the metalloporphyrin in the range of 10(-7) to 10(-9) M. The findings reported here provide strong evidence that the suppression of biliary and serum bilirubin levels and the enhancement of heme excretion in the bile of the normal volunteers examined in this study were due to inhibition of physiological rates of heme oxidation activity by the synthetic heme analog, Sn-protoporphyrin.
Adult↗
Cholestyramine in type IIa hyperlipoproteinemia. Is low-dose treatment feasible?
The present study was undertaken to evaluate the possible lipid-lowering effects of low-dose cholestyramine medication in type IIa hyperlipoproteinemia. A total of 16 patients, 8 with heterozygous familial hypercholesterolemia and 8 with polygenic hypercholesterolemia, were investigated. After an initial 3-month period of dietary treatment, 8 of the patients were randomly selected for medication with 4 g of cholestyramine twice daily, and the other 8 received a dose of 8 g twice daily for 2 months. The regimens were then exchanged, and the patients followed for a further 2 months. Plasma lipids and lipoprotein cholesterol were determined at intervals of 4 weeks. Total plasma cholesterol was reduced by 17% during treatment with 8 g and somewhat more (26%) during treatment with 16 g of cholestyramine daily. The decrease in plasma LDL cholesterol did not differ during treatment with 8 g (27%) and 16 g (31%); no changes in plasma triglycerides, VLDL- or HDL-cholesterol were seen. Although plasma LDL-cholesterol was higher in patients with familial hypercholesterolemia, there was no obvious influence of the genetic origin of hypercholesterolemia on the response. It is concluded that low-dose treatment with cholestyramine lowers, and sometimes normalizes, LDL-cholesterol in hypercholesterolemia. Furthermore, the LDL-cholesterol level obtained during the 16-g dose could be predicted from the response seen during treatment with 8 g of cholestyramine daily.
Adult↗
Metabolism of lipoprotein remnants in humans. Studies during intestinal infusion of fat and cholesterol in subjects with varying expression of the low density lipoprotein receptor.
To study the possible importance of the low density lipoprotein (LDL) receptor in regulating the degree of postprandial lipemia, a cholesterol-rich fat emulsion was infused into the duodenum of subjects who were divided into four groups based on the expected variation in the expression of the LDL receptor: young men (n = 11), elderly men (n = 7), male patients on estrogen therapy (n = 5), and patients with familial hypercholesterolemia (n = 9). In familial hypercholesterolemia, fasting plasma levels of lipoproteins of d less than 1.006 g/ml, intermediate density lipoproteins, and LDLs were increased. During the fat infusion, the cholesterol and triglyceride contents in the d less than 1.006 g/ml fraction increased to a similar extent in all groups, whereas a concomitant reduction of LDL cholesterol levels was observed. The degree of the decrease in LDL cholesterol was positively correlated with the observed increase in triglycerides in the d less than 1.006 g/ml fraction. There were no signs of accumulation of intermediate density lipoproteins during infusion in any of the groups studied. The results indicate that the capacity for clearance of chylomicrons and chylomicron remnants is not affected by variation in LDL receptor expression.
Adult↗