scholarly journals Microencapsulated Genetically EngineeredLactobacillus plantarum80 (pCBH1) for Bile Acid Deconjugation and Its Implication in Lowering Cholesterol

2004 ◽  
Vol 2004 (1) ◽  
pp. 61-69 ◽  
Author(s):  
Mitchell Lawrence Jones ◽  
Hongmei Chen ◽  
Wei Ouyang ◽  
Terrence Metz ◽  
Satya Prakash
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Lactobacillus Plantarum ◽  
Blood Cholesterol ◽  
Bile Salt Hydrolase ◽  
Regular Exercise ◽  
Bile Acid Sequestrants ◽  
Oral Doses ◽  
Glycodeoxycholic Acid ◽  
Conjugated Bile Acids

Cholesterol is known to be a major risk factor for coronary heart disease (CHD). Current treatments for elevated blood cholesterol include dietary management, regular exercise, and drug therapy with fibrates, bile acid sequestrants, and statins. Such therapies, however, are often suboptimal and carry a risk for serious side effects. This study shows that microencapsulatedLactobacillus plantarum80 (pCBH1) cells can efficiently break down and remove bile acids, and establishes a basis for their use in lowering blood serum cholesterol. Results show that microencapsulated LP80 (pCBH1) is able to effectively break down the conjugated bile acids glycodeoxycholic acid (GDCA) and taurodeoxycholic acid (TDCA) with bile salt hydrolase (BSH) activities of 0.19 and 0.08μmol DCA/mg CDW/h respectively. This article also summarizes the physiological interrelationship between bile acids and cholesterol and predicts the oral doses of microencapsulatedLactobacillus plantarum80 (pCBH1) cells required for lowering cholesterol.

scholarly journals Role of Bile Acids in the Regulation of Food Intake, and Their Dysregulation in Metabolic Disease

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1104
Author(s):  
Cong Xie ◽  
Weikun Huang ◽  
Richard L. Young ◽  
Karen L. Jones ◽  
Michael Horowitz ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Peptide Yy ◽  
Glycogen Synthesis ◽  
Hormone Secretion ◽  
Gastrointestinal Hormones ◽  
Farnesoid X Receptor ◽  
Gastrointestinal Hormone ◽  
Bile Acid Sequestrants

Bile acids are cholesterol-derived metabolites with a well-established role in the digestion and absorption of dietary fat. More recently, the discovery of bile acids as natural ligands for the nuclear farnesoid X receptor (FXR) and membrane Takeda G-protein-coupled receptor 5 (TGR5), and the recognition of the effects of FXR and TGR5 signaling have led to a paradigm shift in knowledge regarding bile acid physiology and metabolic health. Bile acids are now recognized as signaling molecules that orchestrate blood glucose, lipid and energy metabolism. Changes in FXR and/or TGR5 signaling modulates the secretion of gastrointestinal hormones including glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), hepatic gluconeogenesis, glycogen synthesis, energy expenditure, and the composition of the gut microbiome. These effects may contribute to the metabolic benefits of bile acid sequestrants, metformin, and bariatric surgery. This review focuses on the role of bile acids in energy intake and body weight, particularly their effects on gastrointestinal hormone secretion, the changes in obesity and T2D, and their potential relevance to the management of metabolic disorders.

scholarly journals Bile Acid Uptake Transporters as Targets for Therapy

2017 ◽  
Vol 35 (3) ◽  
pp. 251-258 ◽  
Author(s):  
Davor Slijepcevic ◽  
Stan F.J. van de Graaf
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Energy Homeostasis ◽  
Sodium Taurocholate ◽  
Hepatic Uptake ◽  
Farnesoid X Receptor ◽  
Acid Uptake ◽  
Bile Acid Uptake ◽  
Uptake Transporters ◽  
Conjugated Bile Acids

Background: Bile acids are potent signaling molecules that regulate glucose, lipid and energy homeostasis predominantly via the bile acid receptors farnesoid X receptor (FXR) and transmembrane G protein-coupled receptor 5 (TGR5). The sodium taurocholate cotransporting polypeptide (NTCP) and the apical sodium dependent bile acid transporter (ASBT) ensure an effective circulation of (conjugated) bile acids. The modulation of these transport proteins affects bile acid localization, dynamics and signaling. The NTCP-specific pharmacological inhibitor myrcludex B inhibits hepatic uptake of conjugated bile acids. Multiple ASBT-inhibitors are already in clinical trials to inhibit intestinal bile acid uptake. Here, we discuss current insights into the consequences of targeting bile acid uptake transporters on systemic and intestinal bile acid dynamics and discuss the possible therapeutic applications that evolve as a result.

Bile Acid Synthesis in the Developing Sheep Liver

1973 ◽  
Vol 45 (3) ◽  
pp. 403-406
Author(s):  
R. A. Smallwood ◽  
P. Jablonski ◽  
J. McK. Watts
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Placental Transfer ◽  
Umbilical Vein ◽  
Acid Synthesis ◽  
Taurocholic Acid ◽  
Secondary Bile Acid ◽  
Radioactive Label ◽  
Sheep Liver ◽  
Conjugated Bile Acids

1. [14C]Cholesterol was administered intravenously via the umbilical vein to foetal sheep in the latter half of gestation, and the incorporation of radioactive label into foetal bile acids was assessed. 2. After 4 days, 0·5–2% of the radioactive label was found in foetal bile. Seventy to eighty per cent of the radioactive label in foetal bile was present as [14C]taurocholic acid and [14C]taurochenodeoxycholic acid. The remainder was [14C]cholesterol. No radioactive label was found in taurodeoxycholic acid, or in any of the glycine-conjugated bile acids. 3. It is concluded that the foetal sheep liver in the second half of gestation synthesizes taurocholic acid and taurochenodeoxycholic acid. However, the secondary bile acid taurodeoxycholic acid and the glycine-conjugated bile acids, present in foetal bile, have been acquired by placental transfer from the mother.

Carrier-mediated transport of conjugated bile acids across the basolateral membrane of biliary epithelial cells

1997 ◽  
Vol 272 (6) ◽  
pp. G1416-G1424 ◽  
Author(s):  
A. Benedetti ◽  
A. Di Sario ◽  
L. Marucci ◽  
G. Svegliati-Baroni ◽  
C. D. Schteingart ◽  
...  
Keyword(s):  
Bile Acid ◽  
Epithelial Cells ◽  
Bile Acids ◽  
Basolateral Membrane ◽  
Organic Anions ◽  
Disulfonic Acid ◽  
Apical Region ◽  
Image Analysis System ◽  
Carrier Mediated Transport ◽  
Conjugated Bile Acids

When secreted into bile, unconjugated dihydroxy bile acids are absorbed passively by cholangiocytes according to the cholehepatic circulation hypothesis. A fraction of these are likely to be conjugated during transcellular transport. Experiments were performed using fluorescent conjugated bile acids to test whether carrier-mediated transport of conjugated bile acids is present in the basolateral domains of polarized cholangiocytes of intrahepatic bile ductules isolated from rat liver. The time course of the cellular localization of cholyl-NBDAB-Gly and chenodeoxycholyl-NBDAB-Gly, which are anionic fluorescent derivatives of the corresponding glycine-conjugated bile acids, was characterized using an image-analysis system. With 0.3-3 microM solutions, fluorescence was present at 1 and 3 min in the basolateral area of cholangiocytes. Staining in the apical region occurred later, with a peak after 15 min of incubation. The basolateral uptake of the two fluorescent bile acids was temperature dependent and Na+ independent, and was not influenced by the addition of amiloride, by lowering of the medium pH to 6.0, or by preincubation with valinomycin. Uptake was partially inhibited by the absence of Cl- or HCO3- in the perfusate, by preincubation with 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), and by the presence of different organic anions or unconjugated and conjugated bile acids in the medium. When cells were preloaded with an ethyl ester of chenodeoxycholyl-NBDAB-Gly, which is hydrolyzed by intracellular esterases, the decrease of cell fluorescence was partly inhibited by H2DIDS, whereas it was stimulated by the presence of 20 microM cholyltaurine in the medium. It is concluded that transport of conjugated bile acid anions across the basolateral membrane of the polarized rat cholangiocyte is carrier mediated. The conjugated bile acid transporter is likely to be an anion exchanger and is likely to be involved in bile secretion whenever conjugated bile acids or other organic anions are transported from the base of the biliary ductular epithelial cells into the plasma of the periductular capillary plexus.

FRI-107-Emerging role of taurine conjugated bile acids in the gut liver axis and on hepatic bile acid receptors in chronic hepatitis C

2019 ◽  
Vol 70 (1) ◽  
pp. e434-e435
Author(s):  
Rabab Oun Ali Anwar Ali ◽  
Gabriella quinn ◽  
kareen hill ◽  
Grace Zhang ◽  
Christopher Koh ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Bile Acid ◽  
Hepatitis C ◽  
Bile Acids ◽  
Chronic Hepatitis C ◽  
Hepatic Bile ◽  
Bile Acid Receptors ◽  
Conjugated Bile Acids

scholarly journals MECHANISMS IN ENDOCRINOLOGY: Bile acid sequestrants in type 2 diabetes: potential effects on GLP1 secretion

2014 ◽  
Vol 171 (2) ◽  
pp. R47-R65 ◽  
Author(s):  
David P Sonne ◽  
Morten Hansen ◽  
Filip K Knop
Keyword(s):  
Type 2 Diabetes ◽  
Bile Acid ◽  
Bile Acids ◽  
G Protein ◽  
Farnesoid X Receptor ◽  
Bile Acid Metabolism ◽  
Bile Acid Sequestrants ◽  
G Protein Coupled

Bile acid sequestrants have been used for decades for the treatment of hypercholesterolaemia. Sequestering of bile acids in the intestinal lumen interrupts enterohepatic recirculation of bile acids, which initiate feedback mechanisms on the conversion of cholesterol into bile acids in the liver, thereby lowering cholesterol concentrations in the circulation. In the early 1990s, it was observed that bile acid sequestrants improved glycaemic control in patients with type 2 diabetes. Subsequently, several studies confirmed the finding and recently – despite elusive mechanisms of action – bile acid sequestrants have been approved in the USA for the treatment of type 2 diabetes. Nowadays, bile acids are no longer labelled as simple detergents necessary for lipid digestion and absorption, but are increasingly recognised as metabolic regulators. They are potent hormones, work as signalling molecules on nuclear receptors and G protein-coupled receptors and trigger a myriad of signalling pathways in many target organs. The most described and well-known receptors activated by bile acids are the farnesoid X receptor (nuclear receptor) and the G protein-coupled cell membrane receptor TGR5. Besides controlling bile acid metabolism, these receptors are implicated in lipid, glucose and energy metabolism. Interestingly, activation of TGR5 on enteroendocrine L cells has been suggested to affect secretion of incretin hormones, particularly glucagon-like peptide 1 (GLP1 (GCG)). This review discusses the role of bile acid sequestrants in the treatment of type 2 diabetes, the possible mechanism of action and the role of bile acid-induced secretion of GLP1 via activation of TGR5.

Enhancing the “Stickiness” of Bile Acids to Cross-Linked Polymers:  A Bioconjugate Approach to the Design of Bile Acid Sequestrants

2000 ◽  
Vol 11 (3) ◽  
pp. 397-400 ◽  
Author(s):  
Lan-hui Zhang ◽  
Vaclav Janout ◽  
Jodi L. Renner ◽  
Maki Uragami ◽  
Steven L. Regen
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Bile Acid Sequestrants
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