Selective biliary lipid secretion at low bile-salt-output rates in the isolated perfused rat liver. Effects of phalloidin.
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ABSTRACT:
SUBMITTER: Rahman K
PROVIDER: S-EPMC1146983 | biostudies-other | 1986 Jul
REPOSITORIES: biostudies-other
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Project description:The output of proteins into bile was studied by using isolated perfused rat livers. Replacement of rat blood with defined perfusion media deprived the liver of rat serum proteins (albumin, immunoglobulin A) and resulted in a rapid decline in the amounts of these proteins in bile. When bovine serum albumin was incorporated into the perfusion medium it appeared in bile within 20 min and the amount in the bile was determined by the concentration of the protein in the perfusion medium. The use of a defined perfusion medium also deprived the livers of bile salts and the amounts of these, and of plasma-membrane enzymes [5'-nucleotidase (EC 3.1.3.5) and phosphodiesterase I], in bile declined rapidly. Introduction of micelle-forming bile salts (taurocholate or glycodeoxycholate) to the perfusion medium 80 min after liver isolation markedly increased the output of plasma-membrane enzymes but had no effect on the other proteins. The magnitude of this response was dependent on the bile salt used and its concentration in bile; there was little effect on plasma-membrane enzyme output until the critical micellar concentration of the bile salt had been exceeded in the bile. A bile salt analogue, taurodehydrocholate, which does not form micelles, did not produce the enhanced output of plasma-membrane enzymes. This work supports the view that the output of plasma-membrane enzymes in bile is a consequence of bile salt output and also provides evidence for mechanisms by which serum proteins enter the bile.
| S-EPMC1154256 | biostudies-other
Project description:The microtubule poison, colchicine, caused an abnormal output of a variety of proteins into rat bile. After 3 h of exposure to the drug, livers were isolated and perfused with media of defined protein composition. There was no essential change in permeability of the hepatobiliary system to proteins (e.g. bovine serum albumin) entering bile from the perfusion fluid. The rat (serum) albumin and fibrinogen that were secreted into bile from colchicine-treated livers were probably derived from the hepatocytes. Disruption of the microtubular system reduces the secretion of proteins at the sinusoidal face of the hepatocyte and results in an accumulation of secretory vesicles in the cytoplasm. It is suggested that under these conditions some of the vesicles discharge their contents into the bile canaliculus.
| S-EPMC1152518 | biostudies-other
Project description:BACKGROUND: Chronic diarrhoea is the clinical hallmark of patients presenting with idiopathic bile acid malabsorption. Its pathogenesis is unknown; colonic water secretion can be induced by dihydroxy bile acids, but it is not known whether enrichment of the bile acid pool with these bile acids occurs in such patients. Furthermore, bile acid malabsorption is known to affect biliary lipid composition, but no information is available for the idiopathic type. AIMS: To verify: (a) whether diarrhoea in patients with idiopathic bile acid malabsorption is associated with enrichment of the bile acid pool with dihydroxy bile acids; and (b) whether supersaturation with cholesterol of duodenal bile occurs in such patients as a result of chronic bile acid depletion. PATIENTS: Thirteen patients with idiopathic bile acid malabsorption diagnosed according to abnormal 75SeHCAT test and absence of other organic diseases, and 23 control subjects. METHODS: Bile rich duodenal fluid was collected during intravenous ceruletide infusion in the fasting state. Biliary lipids were analysed by enzymatic assays and bile acids by high performance liquid chromatography. RESULTS: Patients with idiopathic bile acid malabsorption had a cholesterol saturation index similar to controls. Bile acid composition showed only a decrease in percentage cholic acid (29 (2)% versus 36 (2)%; p<0.05); the dihydroxy:trihydroxy bile acid ratio was similar to controls. CONCLUSIONS: Patients with idiopathic bile acid malabsorption do not have an increased risk of forming cholesterol gallstones. The mechanism of diarrhoea does not seem to depend on an enrichment of the bile acid pool with dihydroxy bile acids.
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Project description:Lipid metabolism can influence host's health. There is increasing evidence for interplay between two key regulating factors in lipid metabolism: bile acids (BAs) and gut microbiota. However, very little is known about how types of different diet-supplemented bile salts (BS) influence this interaction in vivo. We sought to explore these relationships using grass carp (Ctenopharyngodon idellus), which often suffers functional disorder of liver and gallbladder. We studied fluctuations of BAs in the gall and changes of microbial communities in the gut in response to seven different diets: five different BS, chelating BS agent, and control. The BS comprised two primary BS [sodium taurochololate (TCAS) and sodium taurochenodeoxycholate (TCDCAS)], sodium tauroursodeoxycholate (TUDCAS), and two secondary BS [sodium taurodeoxycholate (TDCAS) and sodium taurolithocholate (TLCAS)]. Supplementation of primary BS caused a more significant fluctuation of biliary BAs than secondary BS, and TCAS caused a more prominent increase than TCDCAS and TUDCAS. For the gut microbiota, primary BS tended to increase their diversity and induce community succession, secondary BS resulted in a higher firmicutes/bacteroidetes ratio, while TUDCAS had no significant effects. Changes of the gut microbiota triggered by different types of BS caused alteration in BAs biotransformation. Two-obesity-associated families, Lachnospiraceae and Ruminococcaceae were positively correlated with biliary cholic acid (CA), taurochenodeoxycholic acid (TCDCA), and deoxycholic acid (DCA). As both primary and secondary BS resulted in increased synthesis of toxic secondary Bas by the gut microbiota, future studies should pay closer attention to gut microbiota when considering BA treatment.
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Project description:Bile is an important component of the human gastrointestinal tract with an essential role in food absorption and antimicrobial activities. Enteric bacterial pathogens have developed strategies to sense bile as an environmental cue to regulate virulence genes during infection. We discovered that Vibrio parahaemolyticus VtrC, along with VtrA and VtrB, are required for activating the virulence type III secretion system 2 in response to bile salts. The VtrA/VtrC complex activates VtrB in the presence of bile salts. The crystal structure of the periplasmic domains of the VtrA/VtrC heterodimer reveals a β-barrel with a hydrophobic inner chamber. A co-crystal structure of VtrA/VtrC with bile salt, along with biophysical and mutational analysis, demonstrates that the hydrophobic chamber binds bile salts and activates the virulence network. As part of a family of conserved signaling receptors, VtrA/VtrC provides structural and functional insights into the evolutionarily conserved mechanism used by bacteria to sense their environment.
| S-EPMC4933562 | biostudies-literature
Project description:The human gut microbiota impacts host metabolism and has been implicated in the pathophysiology of obesity and metabolic syndromes. However, defining the roles of specific microbial activities and metabolites on host phenotypes has proven challenging due to the complexity of the microbiome-host ecosystem. Here, we identify strains from the abundant gut bacterial phylum Bacteroidetes that display selective bile salt hydrolase (BSH) activity. Using isogenic strains of wild-type and BSH-deleted Bacteroides thetaiotaomicron, we selectively modulated the levels of the bile acid tauro-?-muricholic acid in monocolonized gnotobiotic mice. B. thetaiotaomicron BSH mutant-colonized mice displayed altered metabolism, including reduced weight gain and respiratory exchange ratios, as well as transcriptional changes in metabolic, circadian rhythm, and immune pathways in the gut and liver. Our results demonstrate that metabolites generated by a single microbial gene and enzymatic activity can profoundly alter host metabolism and gene expression at local and organism-level scales.
| S-EPMC6078496 | biostudies-literature
Project description:The sea lamprey (Petromyzon marinus) is a genetically programmed animal model for biliary atresia, as it loses its bile ducts and gallbladder during metamorphosis. However, in contrast to patients with biliary atresia or other forms of cholestasis who develop progressive disease, the postmetamorphosis lampreys grow normally to adult size. To understand how the adult lamprey thrives without the ability to secrete bile, we examined bile salt homeostasis in larval and adult lampreys. Adult livers were severely cholestatic, with levels of bile salts >1 mM, but no evidence of necrosis, fibrosis, or inflammation. Interestingly, both larvae and adults had normal plasma levels (?10 ?M) of bile salts. In larvae, petromyzonol sulfate (PZS) was the predominant bile salt, whereas the major bile salts in adult liver were sulfated C27 bile alcohols. Cytotoxicity assays revealed that PZS was highly toxic. Pharmacokinetic studies in free-swimming adults revealed that ?35% of intravenously injected bromosulfophthalein (BSP) was eliminated over a 72-hour period. Collection of urine and feces demonstrated that both endogenous and exogenous organic anions, including biliverdin, bile salts, and BSP, were predominantly excreted by way of the kidney, with minor amounts also detected in feces. Gene expression analysis detected marked up-regulation of orthologs of known organic anion and bile salt transporters in the kidney, with lesser effects in the intestine and gills in adults compared to larvae. These findings indicate that adult lampreys tolerate cholestasis by altering hepatic bile salt composition, while maintaining normal plasma bile salt levels predominantly through renal excretion of bile products. Therefore, we conclude that strategies to accelerate renal excretion of bile salt and other toxins should be beneficial for patients with cholestasis. (HEPATOLOGY 2013;57:2418-2426).
| S-EPMC3604052 | biostudies-literature
Project description:The human gut microbiota impacts host metabolism and has been implicated in the pathophysiology of obesity and metabolic syndromes. However, defining the roles of specific microbial activities and metabolites on host phenotypes has proven challenging due to the complexity of the microbiome-host ecosystem. Here, we identify strains from the abundant gut bacterial phylum Bacteroidetes that display selective bile salt hydrolase (BSH) activity. Using isogenic strains of wild-type and BSH-deleted Bacteroides thetaiotaomicron, we selectively modulated the levels of the bile acid tauro-b-muricholic acid in monocolonized gnotobiotic mice. B. thetaiotaomicron BSH mutant-colonized mice displayed altered metabolism, including reduced weight gain and respiratory exchange ratios, as well as transcriptional changes in metabolic, circadian rhythm, and immune pathways in the gut and liver. Our results demonstrate that metabolites generated by a single microbial gene and enzymatic activity can profoundly alter host metabolism and gene expression at local and organism-level scales.
2018-07-19 | GSE112571 | GEO
Project description:The protein concentration in bile from several species is reported. The changes in output of protein, bile salts and several enzymes have been followed in rat bile over a 48 h cannulation period. Bile-salt concentration dropped rapidly owing to interruption of the enterohepatic circulation but the output of protein, lysosomal enzymes [acid phosphatase (EC 3.1.3.2) and beta-D-glucuronidase (EC 3.2.1.31)] and plasma-membrane enzymes [5'-nucleotidase (EC 3.1.3.5) and phosphodiesterase I (EC 3.1.4.1)] was maintained. Liver cell damage, monitored by output of lactate dehydrogenase, was very low throughout. Protein, lysosomal enzymes and plasma-membrane enzymes showed different patterns of output with time, but all showed a net increase between 12 and 24 h. The output of lysosomal and plasma-membrane enzymes was between 1 and 5% of the total liver complement over the first 24 h; if inhibition by biliary components is taken into account the output of some of these enzymes, particularly acid phosphatase, may be greater. Ultracentrifugation of bile showed that as the concentration of bile salts decreases the proportion of plasma-membrane enzymes in a sedimentable form increases. The results are discussed in relation to other studies of biliary proteins and to studies of the perturbation of membranes and cells with bile salts.
| S-EPMC1162961 | biostudies-other
Project description:This study was performed to determine the effects of various organic anions on biliary lipid secretion in rats. We infused bile-salt-pool-depleted rats with sodium taurocholate at a constant rate, with or without various organic anions: Indocyanine Green (ICG), bromosulphophthalein (BSP), BSP-glutathione and Phenol Red (PR). BSP decreased biliary secretion of cholesterol and phospholipids in a dose-dependent manner without affecting bile salt secretion (uncoupling), and this change was fully reversible. In contrast, ICG, BSP-glutathione and PR did not cause such an uncoupling of biliary lipids. In addition, the distribution pattern of each organic anion to various lipid particles was determined by gel-permeation chromatography. BSP was predominantly associated with bile salt micelles, whereas vesicular association was dominant for ICG, and both BSP-glutathione and PR formed only self-aggregations. From these data, we concluded that the uncoupling of biliary lipids from bile salt secretion by BSP resulted from the interaction between BSP and bile salt micelles in the bile canaliculus, and that this interaction inhibited the capacity of bile salts to induce the secretion of phospholipids and cholesterol.
| S-EPMC1133038 | biostudies-other