deoxycholic-acid and Hyperlipidemias

Topics: Bile Acids and Salts; Carbon Isotopes; Carbon Radioisotopes; Chemical Phenomena; Chemistry; Chenodeoxycholic Acid; Cholesterol; Cholic Acids; Chromatography, Gas; Chromatography, Thin Layer; Colorimetry; Deoxycholic Acid; Deuterium; Humans; Hyperlipidemias; Injections, Intravenous; Kinetics; Liver; Models, Biological; Radioisotope Dilution Technique; Time Factors; Tritium

A double-blind controlled trial was carried out to compare the effects of chenodeoxycholic acid (CDCA), ursodeoxycholic acid (UDCA), and placebo on cholesterol and triglyceride levels in patients with endogenous hypertriglyceridemias. The dose of both bile acids was four 150-mg capsules day. Total serum cholesterol levels did not show appreciable changes with any of the treatments. HDL cholesterol was significantly increased after CDCA but not after UDCA or placebo. CDCA feeding was associated with a significant decrease in serum triglyceride levels, whereas the other treatments failed to show an effect. It is concluded that UDCA does not affect serum lipid levels, whereas CDCA lowers serum triglycerides and may be useful in the treatment of endogenous hypertriglyceridemia.

Topics: Adult; Chenodeoxycholic Acid; Cholesterol; Clinical Trials as Topic; Deoxycholic Acid; Double-Blind Method; Female; Humans; Hyperlipidemias; Male; Triglycerides; Ursodeoxycholic Acid

Topics: Chenodeoxycholic Acid; Clinical Trials as Topic; Deoxycholic Acid; Double-Blind Method; Drug Evaluation; Humans; Hyperlipidemias; Prospective Studies; Triglycerides

Postprandial dyslipidemia is a common feature of insulin-resistant states and contributes to increased cardiovascular disease risk. Recently, bile acids have been recognized beyond their emulsification properties as important signaling molecules that promote energy expenditure, improve insulin sensitivity, and lower fasting lipemia. Although bile acid receptors have become novel pharmaceutical targets, their effects on postprandial lipid metabolism remain unclear. Here, we investigated the potential role of bile acids in regulation of postprandial chylomicron production and triglyceride excursion. Healthy C57BL/6 mice were given an intraduodenal infusion of taurocholic acid (TA) under fat-loaded conditions, and circulating lipids were measured. Targeting of bile acid receptors was achieved with GW4064, a synthetic agonist to the farnesoid X receptor (FXR), and deoxycholic acid (DCA), an activator of the Takeda G-protein-coupled receptor 5. TA, GW4064, and DCA treatments all lowered postprandial lipemia. FXR agonism also reduced intestinal triglyceride content and activity of microsomal triglyceride transfer protein, involved in chylomicron assembly. Importantly, TA (but not DCA) effects were largely lost in FXR knockout mice. These bile acid effects are reminiscent of the antidiabetic hormone glucagon-like peptide-1 (GLP-1). Although the GLP-1 receptor agonist exendin-4 retained its ability to acutely lower postprandial lipemia during bile acid sequestration and FXR deficiency, it did raise hepatic expression of the rate-limiting enzyme for bile acid synthesis. Bile acid signaling may be an important mechanism of controlling dietary lipid absorption, and bile acid receptors may constitute novel targets for the treatment of postprandial dyslipidemia.

Topics: Animals; Bile Acids and Salts; Cholesterol 7-alpha-Hydroxylase; Deoxycholic Acid; Exenatide; Gastric Emptying; Gene Expression Regulation; Hyperlipidemias; Insulin; Intestinal Mucosa; Intestines; Isoxazoles; Lipid Metabolism; Male; Mice; Mice, Inbred C57BL; Postprandial Period; Receptors, Cytoplasmic and Nuclear; Receptors, G-Protein-Coupled; Taurocholic Acid

The quantitation of cholesterol in lipoprotein subfractions is valuable in estimating the risk for coronary artery disease, but requires multiple tests. We describe a relatively simple procedure, referred to as the dual HDL/total cholesterol (DHT) assay, which allows the sequential measurement of HDL cholesterol (HDL-C) and total cholesterol (total-C) in a single tube. HDL-C is first measured using a homogeneous assay that utilizes an anti-apolipoprotein B [apo(B)] antibody, which sterically blocks the enzymatic measurement of cholesterol on the non-HDL subfractions. Next, deoxycholate is added, which disrupts the antibody-apo(B) complex and allows the subsequent enzymatic measurement of the remaining cholesterol in the non-HDL subfractions. The DHT assay has an acceptable analytical performance and yields results similar to standard methods: for HDL-C, y(DHT) = 0.98x + 0.19, r=0.90; for total-C, y(DHT) = 1.11x - 0.09, r=0.99. In summary, the DHT assay is a homogeneous assay for both HDL-C and total-C, and provides a simple and cost-effective method for screening for hyperlipidaemia.

Topics: Antibodies; Apolipoproteins B; Bilirubin; Chemistry, Clinical; Cholesterol; Deoxycholic Acid; Hemoglobins; Humans; Hyperlipidemias; Lipoproteins, HDL; Mass Screening; Reproducibility of Results; Time Factors

Topics: Acute Disease; Adult; Aged; Deoxycholic Acid; Female; Humans; Hyperlipidemias; Male; Middle Aged; Pancreatitis; Recurrence; Ursodeoxycholic Acid

The effects of ursodeoxycholic acid on biliary lipid secretion and bile acid kinetics were determined in 12 men. For comparison, eight of the subjects were also treated with chenodeoxycholic acid using a crossover study design. The daily dose of each bile acid was 15 mg/kg body wt; each treatment period lasted for 5-6 wk. Kinetics of cholic acid and chenodeoxycholic acid, hepatic secretion rates of biliary lipids, and lipid composition of concentrated fasting duodenal bile were determined before and at the end of each treatment period. The synthesis rates of cholic acid and chenodeoxycholic acid were increased by approximately 80% and 40%, respectively, during treatment with ursodeoxycholic acid. The fractional catabolic rates of the two bile acids were increased by approximately 50%, whereas the pool sizes remained unchanged. Under similar conditions, administration of chenodeoxycholic acid reduced the pool size as well as the synthesis rate of cholic acid by approximately 70%. Ursodeoxycholic acid reduced the hepatic secretion of cholesterol to a higher extent (approximately 50%) than did chenodeoxycholic acid (approximately 30%). The secretion rates of bile acids and phospholipids remained essentially unchanged during the two treatment periods. Fasting duodenal (gallbladder) bile was unsaturated with cholesterol during both regimens. It is concluded that the two bile acids exert different effects on bile acid metabolism. The enhanced conversion of cholesterol to bile acids observed during ursodeoxycholic acid treatment may at least partly explain why ursodeoxycholic acid can reduce the biliary output of cholesterol without suppressing hepatic cholesterol synthesis.

Topics: Bile; Bile Acids and Salts; Chenodeoxycholic Acid; Cholesterol; Cholic Acid; Cholic Acids; Deoxycholic Acid; Gallbladder; Humans; Hyperlipidemias; Kinetics; Lipid Metabolism; Liver; Male; Triglycerides; Ursodeoxycholic Acid

To clarify whether it is possible to compensate the lithogenic effect of clofibrate on bile without diminishing effect of clofibrate on bile without diminishing its therapeutic value, studies have been performed in 15 patients with hyperlipoproteinaemia. They received clofibrate (1.5 g/day) for three weeks and then a combination of clofibrate (1.5 g/day) + ursodeoxycholic acid (0.75 g/day) for also three weeks. The serum concentrations of cholesterol, triglycerides and total bile acids as well as the biliary lipid composition (bile acids, phospholipids and cholesterol were assessed before the study, after the clofibrate therapy and after the combined treatment. Both therapeutic regimen lowered the serum cholesterol and triglyceride concentrations. The enhanced cholesterol saturation of bile during clofibrate treatment (lithogenic index of bile: 1.39; 0.73-1.40; median and range) was completely abolished by ursodeoxycholic acid (0.90; 0.62-1.27). It is suggested that this combination may be a useful way for the treatment of patients with hyperlipoproteinaemia.

Topics: Adult; Bile; Cholesterol; Clofibrate; Deoxycholic Acid; Drug Therapy, Combination; Female; Humans; Hyperlipidemias; Lipids; Male; Middle Aged; Ursodeoxycholic Acid

Topics: Adult; Aged; Chenodeoxycholic Acid; Cholelithiasis; Deoxycholic Acid; Female; Humans; Hyperlipidemias; Male; Middle Aged; Ursodeoxycholic Acid

Individual serum bile acids were analysed by an improved gas liquid chromatography method in 12 patients with primary hyperlipidaemia. Total serum bile acid concentrations were raised in 10 subjects. Ursodeoxycholic acid was found in all 12 patients. It was present in significantly greater concentrations, accounted for a greater proportion of the total serum bile acids, and occurred more frequently than in patients with various forms of hepatobiliary disease. Patients with hyperlipidaemia had proportionately less deoxycholic acid than controls but more than patients with liver disease. There was proportionately less chenodeoxycholic acid in patients with hypercholesterolaemia, in whom the primary bile acid ratio was raised.

Topics: Bile Acids and Salts; Chenodeoxycholic Acid; Cholic Acids; Deoxycholic Acid; Humans; Hyperlipidemias; Liver Diseases

Combined gas-liquid chromatography-mass spectrometry with specific ion monitoring (mass fragmentography) has been used for assay of cholic acic (C), chenodeoxycholic acid (CD), and deoxycholic acid (D) in human serum. Deuterium-labeled C and D were used as internal standards. The relative standard deviation of duplicate samples was 3, 4, and 7% for C, CD, and D, respectively. The variation within the same individual in the fasting state was small, while the day-to-day variation was greater, especially for the dihydroxy bile acids. In normal control subjects (n = 24), the fasting serum concentration of C averaged 184 +/- 24 ng/ml (mean +/- SEM), and that of CD and D 526 +/- 62 and 407 +/- 44 ng/ml, respectively. Patients with type IIa hyperlipoproteinemia (n = 32) displayed low values of serum bile acids, with a C concentration of 121 +/- 11 ng/ml (P less than 0.01 vs. controls). A similar pattern was seen in patients with a type IIb lipoprotein pattern (n = 10). Subjects with type IV hyperlipoproteinemia (n = 32) showed serum bile acid levels within the normal limits. No relationship to age, sex, or body weight was seen in any of the patient subgroups. Bile acid kinetics were determined with an isotope dilution technique using 14C-labeled C and CD under steady state conditions in control subjects and patients with type IIa and type IV hyperlipoproteinemia. The serum concentration of C correlated significantly to its pool size in control subjects and in patients with type IIa hyperlipoproteinemia but not in patients with type IV. The serum level of CD was not related to CD pool size in any of the subgroups. The data obtained are discussed in relation to present concepts of the enterohepatic circulation. It is suggested that the intestinal content of C in the fasting state is proportional to the total C pool size. The possibility of a defective intestinal uptake of C in some patients with type IV hyperlipoproteinemia is raised.

Topics: Bile Acids and Salts; Body Weight; Chenodeoxycholic Acid; Cholic Acids; Deoxycholic Acid; Female; Gas Chromatography-Mass Spectrometry; Humans; Hyperlipidemias; Male; Middle Aged

Topics: Animals; Chenodeoxycholic Acid; Deoxycholic Acid; Female; Hyperlipidemias; Male; Mice; Rabbits; Rats

Studies were carried out on the effects of polyunsaturated fats on lipid metabolism in 11 patients with hypertriglyceridemia. During cholesterol balance studies performed in eight patients, the feeding of polyunsaturated fats, as compared with saturated fats, caused an increased excretion of endogenous neutral steroids, acidic steroids, or both in most patients. Increases in steroid excretions were marked in some patients and generally exceeded the decrement of cholesterol in the plasma compartment. The finding of a greater excretion of fecal steroids on polyunsaturated fats in hypertriglyceridemic patients contrasts to the lack of change in sterol balance previously reported for patients with familial hypercholesterolemia; however, other workers have found that polyunsaturated fats also enhance steroid excretion in normal subjects. In most of the patients, simultaneous studies were carried out on biliary lipid composition, hourly outputs of biliary lipids, and pool sizes of bile acids. In several but not all patients, fasting gallbladder bile became more lithogenic after institution of polyunsaturated fats. This increased lithogenicity was not due to a decrease in bile acid pools; in no case was the pool decreased by polyunsaturated fats. On the other hand, two patients showed an increased output of biliary cholesterol, and frequently there was an increase in fecal neutral steroids that were derived from cholesterol; thus, polyunsaturated fats may increase bile lithogenicity in some patients through mobilization of cholesterol into bile. Reductions in plasma cholesterol during the feeding of polyunsaturated fats was seen in most patients, and these changes were usually associated with a decrease in concentration of plasma triglycerides. In fact, the degree of cholesterol lowering was closely correlated with the extent of triglyceride reduction. Therefore, in hypertriglyceridimec patients polyunsaturated fats may contribute to cholesterol reduction by changing the metabolism of triglycerides or very low density lipoproteins. The findings of changes in the metabolism of cholesterol, bile acids, and triglycerides in the patients of this study suggests that polyunsaturated fats may cause a lowering of cholesterol through multiple mechanisms, and it seems unlikely that a single action can explain all the effects of these fats on the plasma lipids.

Topics: Adult; Bile; Bile Acids and Salts; Cholesterol; Cholic Acids; Clofibrate; Deoxycholic Acid; Diet; Dietary Fats; Fats, Unsaturated; Feces; Gallbladder; Humans; Hyperlipidemias; Lipid Metabolism; Male; Middle Aged; Sitosterols; Triglycerides

Topics: Bile; Bile Acids and Salts; Chenodeoxycholic Acid; Cholesterol; Cholic Acids; Chromatography, Gas; Deoxycholic Acid; Humans; Hyperlipidemias; Lithocholic Acid; Phytosterols; Stigmasterol