Bile acids in tissues: Binding of lithocholic acid to protein

Lipids ◽  
1978 ◽  
Vol 13 (12) ◽  
pp. 966-970 ◽  
Author(s):  
P. P. Nair ◽  
Robert Solomon ◽  
Joyce Bankoski ◽  
Robert Plapinger
Keyword(s):  
Bile Acids ◽  
Lithocholic Acid

Pharmacological effects of secondary bile acid microparticles in diabetic murine model

2020 ◽  
Vol 16 ◽  
Author(s):  
Armin Mooranian ◽  
Nassim Zamani ◽  
Bozica Kovacevic ◽  
Corina Mihaela Ionescu ◽  
Giuseppe Luna ◽  
...  
Keyword(s):  
Bile Acid ◽  
Blood Glucose ◽  
Bile Acids ◽  
Lithocholic Acid ◽  
Diabetes Treatment ◽  
Secondary Bile Acid ◽  
Glucose Levels ◽  
Anti Inflammatory ◽  
Antidiabetic Effects

Aim: Examine bile acids effects in Type 2 diabetes. Background: In recent studies, the bile acid ursodeoxycholic acid (UDCA) has shown potent anti-inflammatory effects in obese patients while in type 2 diabetics (T2D) levels of the pro-inflammatory bile acid lithocholic acid were increased, and levels of the anti-inflammatory bile acid chenodeoxycholic acid were decreased, in plasma. Objective: Hence, this study aimed to examine applications of novel UDCA nanoparticles in diabetes. Methods: Diabetic balb/c adult mice were divided into three equal groups and gavaged daily with either empty microcapsules, free UDCA, or microencapsulated UDCA over two weeks. Their blood, tissues, urine, and faeces were collected for blood glucose, inflammation, and bile acid analyses. UDCA resulted in modulatory effects on bile acids profile without antidiabetic effects suggesting that bile acid modulation was not directly linked to diabetes treatment. Results: UDCA resulted in modulatory effects on bile acids profile without antidiabetic effects suggesting that bile acid modulation was not directly linked to diabetes treatment. Conclusion: Bile acids modulated the bile profile without affecting blood glucose levels.

scholarly journals Bile Acids Activate NLRP3 Inflammasome, Promoting Murine Liver Inflammation or Fibrosis in a Cell Type-Specific Manner

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2618
Author(s):  
Theresa Maria Holtmann ◽  
Maria Eugenia Inzaugarat ◽  
Jana Knorr ◽  
Lukas Geisler ◽  
Marten Schulz ◽  
...  
Keyword(s):  
Bile Acids ◽  
Liver Damage ◽  
Nlrp3 Inflammasome ◽  
Lithocholic Acid ◽  
Ex Vivo ◽  
Cell Types ◽  
Inflammasome Activation ◽  
Inflammatory Phenotype ◽  
Murine Liver ◽  
A Cell

Bile acids (BA) as important signaling molecules are considered crucial in development of cholestatic liver injury, but there is limited understanding on the involved cell types and signaling pathways. The aim of this study was to evaluate the inflammatory and fibrotic potential of key BA and the role of distinct liver cell subsets focusing on the NLRP3 inflammasome. C57BL/6 wild-type (WT) and Nlrp3−/− mice were fed with a diet supplemented with cholic (CA), deoxycholic (DCA) or lithocholic acid (LCA) for 7 days. Additionally, primary hepatocytes, Kupffer cells (KC) and hepatic stellate cells (HSC) from WT and Nlrp3−/− mice were stimulated with aforementioned BA ex vivo. LCA feeding led to strong liver damage and activation of NLRP3 inflammasome. Ex vivo KC were the most affected cells by LCA, resulting in a pro-inflammatory phenotype. Liver damage and primary KC activation was both ameliorated in Nlrp3-deficient mice or cells. DCA feeding induced fibrotic alterations. Primary HSC upregulated the NLRP3 inflammasome and early fibrotic markers when stimulated with DCA, but not LCA. Pro-fibrogenic signals in liver and primary HSC were attenuated in Nlrp3−/− mice or cells. The data shows that distinct BA induce NLRP3 inflammasome activation in HSC or KC, promoting fibrosis or inflammation.

scholarly journals Effects of clofibrate on some microsomal hydroxylations involved in the formation and metabolism of bile acids in rat liver

1976 ◽  
Vol 156 (2) ◽  
pp. 445-448 ◽  
Author(s):  
B O Angelin ◽  
I Björkhem ◽  
K Einarsson
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Rat Liver ◽  
Lithocholic Acid ◽  
Present Knowledge ◽  
Acid Formation ◽  
Microsomal Metabolism ◽  
Endogenous Cholesterol

1. The liver microsomal metabolism of [4-14C]cholesterol, endogenous cholesterol, 7 α-hydroxy-4-[6 β-3H]cholesten-3-one, 5-β-[7 β-3H]cholestane-3 α, 7 α-diol and [3H]lithocholic acid was studdied in control and clofibrate (ethyl p-chlorophenoxyisobutyrate)-treated rats. 2. The extent of 7 α-hydroxylation of exogenous [414C]cholesterol and endogenous cholesterol, the latter determined with a mass fragmentographic technique, was the same in the two groups of rats. The extent of 12 α-hydroxylation of 7 α-hydroxy-4-cholesten-3-one and 5 β-cholestane-3 α, 7 α-diol was increased by about 60 and 120% respectively by clofibrate treatment. The 26-hydroxylation of 5 β-cholestane-3 α, 7 α-diol was not significantly affected by clofibrate. The 6 β-hydroxylation of lithocholic acid was about 80% higher in the clofibrate-treated animals than in the controls. 3. The results are discussed in the context of present knowledge about the liver microsomal hydroxylating system and bile acid formation in patients with hypercholesterolaemia, treated with clofibrate.

Abstract 153: Bile Acid Receptor TGR5 Agonism Represents Anti-inflammatory Effects via Stimulating Nitric Oxide Production in Vascular Endothelial Cells

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Taiki Kida ◽  
Yoshiki Tsubosaka ◽  
Masatoshi Hori ◽  
Hiroshi Ozaki ◽  
Takahisa Murata
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Bile Acids ◽  
Inflammatory Responses ◽  
Vascular Endothelial Cells ◽  
Lithocholic Acid ◽  
Signal Pathways ◽  
No Production ◽  
Vascular Endothelial ◽  
Anti Inflammatory

Objective TGR5, a membrane-bound, G-protein-coupled receptor for bile acids, is known to be involved in regulation of energy homeostasis and inflammation. However, little is known about the function of TGR5 in vascular endothelial cells. In the present study, we examined whether TGR5 agonism represents anti-inflammatory effects in vascular endothelial cells focusing on nitric oxide (NO) production. Methods and Results In human umbilical vein endothelial cells (HUVECs), treatment with taurolithocholic acid (TLCA), which has the highest affinity to TGR5 among various bile acids, significantly reduced tumor necrosis factor (TNF)-α-induced vascular cell adhesion molecule (VCAM)-1 protein expression and adhesion of human monocytes, U937. These effects were abrogated by a NO synthase (NOS) inhibitor, N G -Monomethyl-L-arginine (L-NMMA). In bovine aortic endothelial cells (BAECs), treatment with TLCA as well as lithocholic acid, which also has high affinity to TGR5, significantly increased the NO production. In contrast, deoxycholic acid and chenodeoxycholic acid, which possess low affinity to TGR5, did not affect the NO production. Gene depletion of TGR5 by siRNA transfection abolished TLCA-induced NO production in BAECs. TLCA-induced NO production was also observed in HUVECs measured as intracellular cGMP accumulation. We next investigated the signal pathways responsible for the TLCA-induced NO production in endothelial cells. Treatment with TLCA increased endothelial NOS (eNOS) ser1177 phosphorylation in HUVECs. This response was accompanied by increased Akt ser473 phosphorylation and intracellular Ca 2+ ([Ca 2+ ] i ). Treatment with phosphoinositide 3-kinase (PI3K) inhibitor, LY294002, or blockade of calcium channel with La 3+ , significantly decreased TLCA-induced eNOS ser1177 phosphorylation and subsequent NO production. Conclusion These results indicate that TGR5 agonism can mediate anti-inflammatory responses by suppressing VCAM-1 expression and monocytes adhesion to endothelial cells. This function is dependent on NO production via Akt activation and [Ca 2+ ] i increase.

Lipid, Bile Acid, Water and Dry Matter Content of the Intestinal Tract of Domestic Ducks with Reference to the Habitat of Polymorphus Minutus (Acanthocephala)

1970 ◽  
Vol 52 (2) ◽  
pp. 437-445
Author(s):  
D. W. T. CROMPTON ◽  
M. C. NESHEIM
Keyword(s):  
Bile Acids ◽  
Intestinal Tract ◽  
Lithocholic Acid ◽  
Posterior Part ◽  
Dry Weight ◽  
Matter Content ◽  
Gas Liquid Chromatography ◽  
Dry Matter Content ◽  
Domestic Ducks ◽  
Acanthocephalan Parasite

1. The distributions of total material, water, lipid and bile salts in the intestine of domestic ducks feeding ad libitum have been determined. 2. Most material accumulates in the posterior part of the intestine and the duodenal region appears to be wetter than the rest of the intestine. 3. When ducks feed on a diet with a lipid content of 4% of the dry weight, the highest concentration of lipid detected in the intestine was 5% of the dry weight of the ntestinal material. Lipid appears to be absorbed in the anterior half of the intestine. 4. Bile acids accumulate in the posterior part of the intestine where concentrations as high as 5.18 mg./g. of intestinal contents were detected. The evidence indicates that bile acids are absorbed in the posterior part of the intestine. 6. The bile acids of bile from the gallbladders of ducks have been identified by means of gas-liquid chromatography. Cholic acid, chenodeoxycholic acid, lithocholic acid and some unidentified substances were found to form 16, 59, 17 and 8%, respectively, of the bile acids. 6. The results are discussed with reference to Polymorphus nunutus, an acanthocephalan parasite of ducks.

scholarly journals Symmetrically substituted dichlorophenes inhibit N-acyl-phosphatidylethanolamine phospholipase D

2020 ◽  
Vol 295 (21) ◽  
pp. 7289-7300 ◽  
Author(s):  
Geetika Aggarwal ◽  
Jonah E. Zarrow ◽  
Zahra Mashhadi ◽  
C. Robb Flynn ◽  
Paige Vinson ◽  
...  
Keyword(s):  
Bile Acids ◽  
Phospholipase D ◽  
Cultured Cells ◽  
Lithocholic Acid ◽  
Hek293 Cells ◽  
Serum Lipase ◽  
Structure Activity ◽  
Molecule Inhibitor ◽  
Streptomyces Chromofuscus

N-Acyl-phosphatidylethanolamine phospholipase D (NAPE-PLD) (EC 3.1.4.4) catalyzes the final step in the biosynthesis of N-acyl-ethanolamides. Reduced NAPE-PLD expression and activity may contribute to obesity and inflammation, but a lack of effective NAPE-PLD inhibitors has been a major obstacle to elucidating the role of NAPE-PLD and N-acyl-ethanolamide biosynthesis in these processes. The endogenous bile acid lithocholic acid (LCA) inhibits NAPE-PLD activity (with an IC50 of 68 μm), but LCA is also a highly potent ligand for TGR5 (EC50 0.52 μm). Recently, the first selective small-molecule inhibitor of NAPE-PLD, ARN19874, has been reported (having an IC50 of 34 μm). To identify more potent inhibitors of NAPE-PLD, here we used a quenched fluorescent NAPE analog, PED-A1, as a substrate for recombinant mouse Nape-pld to screen a panel of bile acids and a library of experimental compounds (the Spectrum Collection). Muricholic acids and several other bile acids inhibited Nape-pld with potency similar to that of LCA. We identified 14 potent Nape-pld inhibitors in the Spectrum Collection, with the two most potent (IC50 = ∼2 μm) being symmetrically substituted dichlorophenes, i.e. hexachlorophene and bithionol. Structure–activity relationship assays using additional substituted dichlorophenes identified key moieties needed for Nape-pld inhibition. Both hexachlorophene and bithionol exhibited significant selectivity for Nape-pld compared with nontarget lipase activities such as Streptomyces chromofuscus PLD or serum lipase. Both also effectively inhibited NAPE-PLD activity in cultured HEK293 cells. We conclude that symmetrically substituted dichlorophenes potently inhibit NAPE-PLD in cultured cells and have significant selectivity for NAPE-PLD versus other tissue-associated lipases.

scholarly journals Sulphation of lithocholic acid in the colon-carcinoma cell line CaCo-2

1999 ◽  
Vol 343 (3) ◽  
pp. 533-539 ◽  
Author(s):  
Bente HALVORSEN ◽  
Bengt Frode KASE ◽  
Kristian PRYDZ ◽  
Sedegheh GARAGOZLIAN ◽  
Marianne S. ANDRESEN ◽  
...  
Keyword(s):  
Bile Acids ◽  
Cell Line ◽  
Colon Carcinoma ◽  
Carcinoma Cell ◽  
Lithocholic Acid ◽  
Human Colon ◽  
Carcinoma Cell Line ◽  
Gel Chromatography ◽  
Colon Carcinoma Cell Line ◽  
Increased Risk

High levels of bile acids in the colon may correlate with an increased risk of colon cancer, but the underlying mechanisms are not known. Proteoglycan structures have been shown to change when human colon cells differentiate in vitro. The expression of [35S]sulphated molecules was used as a phenotypic marker to study the effects of bile acids on the human-colon-carcinoma cell line CaCo-2. [35S]sulphated compounds were isolated from the medium of cell fractions of cells metabolically labelled with [35S]sulphate in the absence and presence of cholic acid, deoxycholic acid, chenodeoxycholic acid and lithocholic acid (LA). Labelled molecules were analysed by gel chromatography, HPLC and SDS/PAGE in combination with chemical and enzymic methods. The expression of 35S-labelled proteoglycans was not affected by any of the bile acids tested. However, the level of sulphated metabolites increased 7-18-fold in different experiments during a 22 h labelling period in the presence of an LA concentration of 10 μg/ml (26.6 nmol/ml) compared with controls. Further analyses showed that this was due, at least in part, to the sulphation of LA itself. This sulphation of LA was a rapid process followed by secretion back to the medium. Brefeldin A did not reduce the sulphation of LA, indicating that this conversion takes place in the cytosol, rather than in the Golgi apparatus of the CaCo-2 cells. LA in colon may be sulphated efficiently by the colonocytes to reduce the toxic effects of this particular bile acid. Sulphation may possibly be an important protective mechanism in the colon.

scholarly journals Human gut bacteria produce TH17-modulating bile acid metabolites

2021 ◽  
Author(s):  
Donggi Paik ◽  
Lina Yao ◽  
Yancong Zhang ◽  
Sena Bae ◽  
Gabriel D. D'Agostino ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Lithocholic Acid ◽  
Retinoic Acid Receptor ◽  
Gut Bacteria ◽  
Orphan Nuclear Receptor ◽  
Human Gut ◽  
Secondary Bile Acid ◽  
Bowel Diseases ◽  
And Function

The microbiota plays a pivotal role in gut immune homeostasis. Bacteria influence the development and function of host immune cells, including T helper cells expressing interleukin-17a (TH17 cells). We previously reported that the bile acid metabolite 3-oxolithocholic acid (3-oxoLCA) inhibits TH17 cell differentiation. While it was suggested that gut-residing bacteria produce 3-oxoLCA, the identity of such bacteria was unknown. Furthermore, it was not clear whether 3-oxoLCA and other immunomodulatory bile acids are associated with gut inflammatory pathologies in humans. Using a high-throughput screen, we identified human gut bacteria and corresponding enzymes that convert the secondary bile acid lithocholic acid into 3-oxoLCA as well as the abundant gut metabolite isolithocholic acid (isoLCA). Like 3-oxoLCA, isoLCA suppressed TH17 differentiation by inhibiting RORγt (retinoic acid receptor-related orphan nuclear receptor γt), a key TH17 cell-promoting transcription factor. Levels of both 3-oxoLCA and isoLCA and the 3α-hydroxysteroid dehydrogenase (3α-HSDH) genes required for their biosynthesis were significantly reduced in patients with inflammatory bowel diseases (IBD). Moreover, levels of these bile acids were inversely correlated with expression of TH17 cell-associated genes. Overall, our data suggest that bacterially produced TH17 cell-inhibitory bile acids may reduce the risk of autoimmune and inflammatory disorders such as IBD.

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