scholarly journals Bile Acid Dysregulation Is Intrinsically Related to Cachexia in Tumor-Bearing Mice

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6389
Author(s):  
Morgane M. Thibaut ◽  
Justine Gillard ◽  
Adeline Dolly ◽  
Martin Roumain ◽  
Isabelle A. Leclercq ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Cancer Cachexia ◽  
Carcinoma Cells ◽  
Hepatic Inflammation ◽  
Colon Carcinoma Cells ◽  
Pathological Conditions ◽  
Host Metabolism ◽  
G Protein Coupled ◽  
Bile Acid Secretion

Bile acids exert diverse actions on host metabolism and immunity through bile acid-activated receptors, including Takeda G protein-coupled receptor 5 (TGR5). We have recently evidenced an alteration in bile acids in cancer cachexia, an inflammatory and metabolic syndrome contributing to cancer death. This current study aims to further explore the links emerging between bile acids and cancer cachexia. First, we showed that bile flow is reduced in cachectic mice. Next, comparing mice inoculated with cachexia-inducing and with non-cachexia-inducing C26 colon carcinoma cells, we demonstrated that alterations in the bile acid pathways and profile are directly associated with cachexia. Finally, we performed an interventional study using ursodeoxycholic acid (UDCA), a compound commonly used in hepatobiliary disorders, to induce bile acid secretion and decrease inflammation. We found that UDCA does not improve hepatic inflammation and worsens muscle atrophy in cachectic mice. This exacerbation of the cachectic phenotype upon UDCA was accompanied by a decreased TGR5 activity, suggesting that TGR5 agonists, known to reduce inflammation in several pathological conditions, could potentially counteract cachectic features. This work brings to light major evidence sustaining the emerging links between bile acids and cancer cachexia and reinforces the interest in studying bile acid-activated receptors in this context.

scholarly journals Recent advances in understanding bile acid homeostasis

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 2029 ◽  
Author(s):  
John YL Chiang
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Farnesoid X Receptor ◽  
Recent Advances ◽  
Bile Acid Pool Size ◽  
Bile Acid Receptor ◽  
Acid Toxicity ◽  
G Protein Coupled

Bile acids are derived from cholesterol to facilitate intestinal nutrient absorption and biliary secretion of cholesterol. Recent studies have identified bile acids as signaling molecules that activate nuclear farnesoid X receptor (FXR) and membrane G protein-coupled bile acid receptor-1 (Gpbar-1, also known as TGR5) to maintain metabolic homeostasis and protect liver and other tissues and cells from bile acid toxicity. Bile acid homeostasis is regulated by a complex mechanism of feedback and feedforward regulation that is not completely understood. This review will cover recent advances in bile acid signaling and emerging concepts about the classic and alternative bile acid synthesis pathway, bile acid composition and bile acid pool size, and intestinal bile acid signaling and gut microbiome in regulation of bile acid homeostasis.

Differing effects of norcholate and cholate on bile flow and biliary lipid secretion in the rat

1984 ◽  
Vol 246 (1) ◽  
pp. G67-G71
Author(s):  
E. R. O'Maille ◽  
S. V. Kozmary ◽  
A. F. Hofmann ◽  
D. Gurantz
Keyword(s):  
Bile Acid ◽  
Acid Secretion ◽  
Bile Acids ◽  
Bile Flow ◽  
Critical Micellar Concentration ◽  
Biliary Lipid ◽  
Lipid Secretion ◽  
Unit Increase ◽  
Cholesterol Secretion ◽  
Bile Acid Secretion

The effects of norcholate (a C23 bile acid that differs from cholate in having a side chain containing four rather than five carbon atoms) on bile flow and biliary lipid secretion were compared with those of cholate, using the anesthetized rat with a bile fistula. Norcholate and cholate were infused intravenously over the range of 0.6-6.0 mumol X min-1 X kg-1. Both bile acids were quantitatively secreted into bile; norcholate was secreted predominantly in unconjugated form in contrast to cholate, which was secreted predominantly as its taurine or glycine conjugates. The increase in bile flow per unit increase in bile acid secretion induced by norcholate infusion [17 +/- 3.2 (SD) microliters/mumol, n = 8] was much greater than that induced by cholate infusion (8.6 +/- 0.9 microliters/mumol, n = 9) (P less than 0.001). Both bile acids induced phospholipid and cholesterol secretion. For an increase in bile acid secretion (above control values) of 1 mumol X min-1 X kg-1, the increases in phospholipid secretion [0.052 +/- 0.024 (SD) mumol X min-1 X kg-1, n = 9] and cholesterol secretion (0.0071 +/- 0.0033 mumol X min-1 X kg-1, n = 9) induced by norcholate infusion were much less than those induced by cholate infusion (0.197 +/- 0.05 mumol X min-1 X kg-1, n = 9, and 0.024 +/- 0.011 mumol X min-1 X kg-1, n = 9, respectively; P less than 0.001 for both phospholipid and cholesterol). The strikingly different effects of norcholate on bile flow and biliary lipid secretion were attributed mainly to its possessing a considerably higher critical micellar concentration than cholate.

scholarly journals Overview of Bile Acids Signaling and Perspective on the Signal of Ursodeoxycholic Acid, the Most Hydrophilic Bile Acid, in the Heart

Biomolecules ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 159 ◽  
Author(s):  
Noorul Izzati Hanafi ◽  
Anis Syamimi Mohamed ◽  
Siti Hamimah Sheikh Abdul Kadir ◽  
Mohd Hafiz Dzarfan Othman
Keyword(s):  
Heart Failure ◽  
Bile Acid ◽  
Chronic Heart Failure ◽  
Ursodeoxycholic Acid ◽  
Bile Acids ◽  
G Protein ◽  
Hormone Receptors ◽  
Nuclear Hormone Receptors ◽  
Heart Failure Patients ◽  
G Protein Coupled

Bile acids (BA) are classically known as an important agent in lipid absorption and cholesterol metabolism. Nowadays, their role in glucose regulation and energy homeostasis are widely reported. BAs are involved in various cellular signaling pathways, such as protein kinase cascades, cyclic AMP (cAMP) synthesis, and calcium mobilization. They are ligands for several nuclear hormone receptors, including farnesoid X-receptor (FXR). Recently, BAs have been shown to bind to muscarinic receptor and Takeda G-protein-coupled receptor 5 (TGR5), both G-protein-coupled receptor (GPCR), independent of the nuclear hormone receptors. Moreover, BA signals have also been elucidated in other nonclassical BA pathways, such as sphingosine-1-posphate and BK (large conductance calcium- and voltage activated potassium) channels. Hydrophobic BAs have been proven to affect heart rate and its contraction. Elevated BAs are associated with arrhythmias in adults and fetal heart, and altered ratios of primary and secondary bile acid are reported in chronic heart failure patients. Meanwhile, in patients with liver cirrhosis, cardiac dysfunction has been strongly linked to the increase in serum bile acid concentrations. In contrast, the most hydrophilic BA, known as ursodeoxycholic acid (UDCA), has been found to be beneficial in improving peripheral blood flow in chronic heart failure patients and in protecting the heart against reperfusion injury. This review provides an overview of BA signaling, with the main emphasis on past and present perspectives on UDCA signals in the heart.

scholarly journals Metabolic consequences of ileal interruption of the enterohepatic circulation of bile acids

2020 ◽  
Vol 319 (5) ◽  
pp. G619-G625
Author(s):  
Ivo P. van de Peppel ◽  
Henkjan J. Verkade ◽  
Johan W. Jonker
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Enterohepatic Circulation ◽  
Current Knowledge ◽  
Whole Body ◽  
Novel Studies ◽  
Sodium Dependent ◽  
Bile Acid Transporter ◽  
Bile Acid Secretion ◽  
Different Levels

The enterohepatic circulation of bile acids comprises a tightly regulated process of hepatic bile acid secretion, intestinal reabsorption and transport back to the liver. Disruption of this process has significant consequences for gastrointestinal, liver and whole body homeostasis and therefore offers opportunities for therapeutic intervention. In this review we discuss the effects of (pharmacological) interruption of the enterohepatic circulation at different levels. Recently, several studies have been published on ileal interruption of the enterohepatic circulation of bile acids, targeting the apical-sodium dependent bile acid transporter (ASBT, SLC10A2), as therapy for various diseases. However, ambiguous results have been reported and in-depth mechanistic insights are lacking. Here we discuss these novel studies and review the current knowledge on the consequences of ASBT inhibition and its potential effects on physiology and metabolism.

scholarly journals Bile acids induce MUC2 overexpression in human colon carcinoma cells

Cancer ◽  
2005 ◽  
Vol 103 (8) ◽  
pp. 1606-1614 ◽  
Author(s):  
Shumei Song ◽  
James C. Byrd ◽  
Ja Seok Koo ◽  
Robert S. Bresalier
Keyword(s):  
Bile Acids ◽  
Colon Carcinoma ◽  
Human Colon ◽  
Carcinoma Cells ◽  
Colon Carcinoma Cells ◽  
Human Colon Carcinoma

Effect of primary bile acids on bile lipid secretion from perfused dog liver

1975 ◽  
Vol 229 (3) ◽  
pp. 714-720 ◽  
Author(s):  
NE Hoffman ◽  
DE Donald ◽  
AF Hosmann
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Liver Perfusion ◽  
Biliary Lipid ◽  
Hepatic Extraction ◽  
Perfusion Technique ◽  
Lipid Secretion ◽  
Cholesterol Secretion ◽  
Dog Liver ◽  
Bile Acid Secretion

An isolated canine liver perfusion technique featuring a second dog as the pump oxygenator was used to compare biliary lipid secretion during randomized, steady-state perfusions at two different rates of cholyl taurine or chenodeoxycholyl taurine infusions. The hepatic extraction of the trihydroxy-conjugated bile acid was considerably greater than that of the dihydroxy conjugate, possibly explained by ultrafiltration experiments which indicated that cholyl taurine was less protein bound than chenodeoxycholyl taurine. Both bile acids induced phospholipid and cholesterol secretion that was linearly proportional to bile acid secretion. However, each mole of secreted chenodeoxycholyl taurine induced a greater relative secretion of phospholipid and cholesterol than did that of cholyl taurine. Thus in the canine liver, the two primary bile acids are extracted at different rates and induce biliary secretion of different relative lipid composition.

Sa1444 Bile Acids Cause Relaxation of Human Gallbladder Through G Protein-Coupled Bile Acid Receptor

2012 ◽  
Vol 142 (5) ◽  
pp. S-307
Author(s):  
Ming-Che Lee ◽  
Ying-Chin Yang ◽  
Yen-Cheng Chen ◽  
Shih-Che Huang
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
G Protein ◽  
Human Gallbladder ◽  
Acid Receptor ◽  
Bile Acid Receptor ◽  
G Protein Coupled

scholarly journals Bile Acids Trigger GLP-1 Release Predominantly by Accessing Basolaterally Located G Protein–Coupled Bile Acid Receptors

Endocrinology ◽  
2015 ◽  
Vol 156 (11) ◽  
pp. 3961-3970 ◽  
Author(s):  
Cheryl A. Brighton ◽  
Juraj Rievaj ◽  
Rune E. Kuhre ◽  
Leslie L. Glass ◽  
Kristina Schoonjans ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
G Protein ◽  
Primary Cultures ◽  
Hormone Secretion ◽  
Intracellular Camp ◽  
Ussing Chambers ◽  
L Cells ◽  
Gut Hormone ◽  
G Protein Coupled

Bile acids are well-recognized stimuli of glucagon-like peptide-1 (GLP-1) secretion. This action has been attributed to activation of the G protein–coupled bile acid receptor GPBAR1 (TGR5), although other potential bile acid sensors include the nuclear farnesoid receptor and the apical sodium-coupled bile acid transporter ASBT. The aim of this study was to identify pathways important for GLP-1 release and to determine whether bile acids target their receptors on GLP-1–secreting L-cells from the apical or basolateral compartment. Using transgenic mice expressing fluorescent sensors specifically in L-cells, we observed that taurodeoxycholate (TDCA) and taurolithocholate (TLCA) increased intracellular cAMP and Ca2+. In primary intestinal cultures, TDCA was a more potent GLP-1 secretagogue than taurocholate (TCA) and TLCA, correlating with a stronger Ca2+ response to TDCA. Using small-volume Ussing chambers optimized for measuring GLP-1 secretion, we found that both a GPBAR1 agonist and TDCA stimulated GLP-1 release better when applied from the basolateral than from the luminal direction and that luminal TDCA was ineffective when intestinal tissue was pretreated with an ASBT inhibitor. ASBT inhibition had no significant effect in nonpolarized primary cultures. Studies in the perfused rat gut confirmed that vascularly administered TDCA was more effective than luminal TDCA. Intestinal primary cultures and Ussing chamber–mounted tissues from GPBAR1-knockout mice did not secrete GLP-1 in response to either TLCA or TDCA. We conclude that the action of bile acids on GLP-1 secretion is predominantly mediated by GPBAR1 located on the basolateral L-cell membrane, suggesting that stimulation of gut hormone secretion may include postabsorptive mechanisms.

scholarly journals Bile acid receptors FXR and TGR5 signaling in fatty liver diseases and therapy

2020 ◽  
Vol 318 (3) ◽  
pp. G554-G573 ◽  
Author(s):  
John Y. L. Chiang ◽  
Jessica M. Ferrell
Keyword(s):  
Bile Acid ◽  
Fatty Liver ◽  
Bile Acids ◽  
G Protein ◽  
Liver Diseases ◽  
Metabolic Diseases ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Bile Acid Receptors ◽  
G Protein Coupled

Bile acid synthesis is the most significant pathway for catabolism of cholesterol and for maintenance of whole body cholesterol homeostasis. Bile acids are physiological detergents that absorb, distribute, metabolize, and excrete nutrients, drugs, and xenobiotics. Bile acids also are signal molecules and metabolic integrators that activate nuclear farnesoid X receptor (FXR) and membrane Takeda G protein-coupled receptor 5 (TGR5; i.e., G protein-coupled bile acid receptor 1) to regulate glucose, lipid, and energy metabolism. The gut-to-liver axis plays a critical role in the transformation of primary bile acids to secondary bile acids, in the regulation of bile acid synthesis to maintain composition within the bile acid pool, and in the regulation of metabolic homeostasis to prevent hyperglycemia, dyslipidemia, obesity, and diabetes. High-fat and high-calorie diets, dysbiosis, alcohol, drugs, and disruption of sleep and circadian rhythms cause metabolic diseases, including alcoholic and nonalcoholic fatty liver diseases, obesity, diabetes, and cardiovascular disease. Bile acid-based drugs that target bile acid receptors are being developed for the treatment of metabolic diseases of the liver.

Sign in / Sign up

Export Citation Format

Share Document