Faculty Opinions recommendation of Differential regulation of bile acid and cholesterol metabolism by the farnesoid X receptor in Ldlr -/- mice versus hamsters.

2013 ◽  
Author(s):  
Guorong Xu ◽  
Monica Saumoy
Keyword(s):  
Bile Acid ◽  
Cholesterol Metabolism ◽  
Differential Regulation ◽  
Farnesoid X Receptor

scholarly journals Differential regulation of bile acid and cholesterol metabolism by the farnesoid X receptor inLdlr−/−mice versus hamsters

2013 ◽  
Vol 54 (5) ◽  
pp. 1283-1299 ◽  
Author(s):  
Christophe Gardès ◽  
Evelyne Chaput ◽  
Andreas Staempfli ◽  
Denise Blum ◽  
Hans Richter ◽  
...  
Keyword(s):  
Bile Acid ◽  
Cholesterol Metabolism ◽  
Differential Regulation ◽  
Farnesoid X Receptor

scholarly journals Lactobacillus delbrueckii Interfere With Bile Acid Enterohepatic Circulation to Regulate Cholesterol Metabolism of Growing–Finishing Pigs via Its Bile Salt Hydrolase Activity

2020 ◽  
Vol 7 ◽  
Author(s):  
Gaifeng Hou ◽  
Wei Peng ◽  
Liangkai Wei ◽  
Rui Li ◽  
Yong Yuan ◽  
...  
Keyword(s):  
Bile Acid ◽  
Enterohepatic Circulation ◽  
Cholesterol Metabolism ◽  
Binding Protein ◽  
Density Lipoprotein ◽  
Lactobacillus Delbrueckii ◽  
Farnesoid X Receptor ◽  
Bile Salt Hydrolase ◽  
Lipoprotein Receptor ◽  
Density Lipoprotein Receptor

Microbiota-targeted therapies for hypercholesterolemia get more and more attention and are recognized as an effective strategy for preventing and treating cardiovascular disease. The experiment was conducted to investigate the cholesterol-lowering mechanism of Lactobacillus delbrueckii in a pig model. Twelve barrows (38.70 ± 5.33 kg) were randomly allocated to two groups and fed corn–soybean meal diets with either 0% (Con) or 0.1% Lactobacillus delbrueckii (Con + LD) for 28 days. L. delbrueckii–fed pigs had lower serum contents of total cholesterol (TC), total bile acids (TBAs), and triglyceride, but higher fecal TC and TBA excretion. L. delbrueckii treatment increased ileal Lactobacillus abundance and bile acid (BA) deconjugation and affected serum and hepatic BA composition. Dietary L. delbrueckii downregulated the gene expression of ileal apical sodium-dependent bile acid transporter (ASBT) and ileal bile acid binding protein (IBABP), and hepatic farnesoid X receptor (FXR), fibroblast growth factor (FGF19), and small heterodimer partner (SHP), but upregulated hepatic high-density lipoprotein receptor (HDLR), low-density lipoprotein receptor (LDLR), sterol regulatory element binding protein-2 (SREBP-2), and cholesterol-7α hydroxylase (CYP7A1) expression. Our results provided in vivo evidence that L. delbrueckii promote ileal BA deconjugation with subsequent fecal TC and TBA extraction by modifying ileal microbiota composition and induce hepatic BA neosynthesis via regulating gut–liver FXR–FGF19 axis.

scholarly journals Differential regulation of bile acid homeostasis by the farnesoid X receptor in liver and intestine

2007 ◽  
Vol 48 (12) ◽  
pp. 2664-2672 ◽  
Author(s):  
Insook Kim ◽  
Sung-Hoon Ahn ◽  
Takeshi Inagaki ◽  
Mihwa Choi ◽  
Shinji Ito ◽  
...  
Keyword(s):  
Bile Acid ◽  
Differential Regulation ◽  
Farnesoid X Receptor

scholarly journals Colesevelam suppresses hepatic glycogenolysis by TGR5-mediated induction of GLP-1 action in DIO mice

2013 ◽  
Vol 304 (4) ◽  
pp. G371-G380 ◽  
Author(s):  
Matthew J. Potthoff ◽  
Austin Potts ◽  
Tianteng He ◽  
João A. G. Duarte ◽  
Ronald Taussig ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Molecular Mechanisms ◽  
Cholesterol Metabolism ◽  
Farnesoid X Receptor ◽  
In Vitro Assays ◽  
Hepatic Glycogen ◽  
Acid Activation ◽  
Acid Receptor ◽  
Bile Acid Receptor

Bile acid sequestrants are nonabsorbable resins designed to treat hypercholesterolemia by preventing ileal uptake of bile acids, thus increasing catabolism of cholesterol into bile acids. However, sequestrants also improve hyperglycemia and hyperinsulinemia through less characterized metabolic and molecular mechanisms. Here, we demonstrate that the bile acid sequestrant, colesevelam, significantly reduced hepatic glucose production by suppressing hepatic glycogenolysis in diet-induced obese mice and that this was partially mediated by activation of the G protein-coupled bile acid receptor TGR5 and glucagon-like peptide-1 (GLP-1) release. A GLP-1 receptor antagonist blocked suppression of hepatic glycogenolysis and blunted but did not eliminate the effect of colesevelam on glycemia. The ability of colesevelam to induce GLP-1, lower glycemia, and spare hepatic glycogen content was compromised in mice lacking TGR5. In vitro assays revealed that bile acid activation of TGR5 initiates a prolonged cAMP signaling cascade and that this signaling was maintained even when the bile acid was complexed to colesevelam. Intestinal TGR5 was most abundantly expressed in the colon, and rectal administration of a colesevelam/bile acid complex was sufficient to induce portal GLP-1 concentration but did not activate the nuclear bile acid receptor farnesoid X receptor (FXR). The beneficial effects of colesevelam on cholesterol metabolism were mediated by FXR and were independent of TGR5/GLP-1. We conclude that colesevelam administration functions through a dual mechanism, which includes TGR5/GLP-1-dependent suppression of hepatic glycogenolysis and FXR-dependent cholesterol reduction.

scholarly journals Liver Bile Acid Changes in Mouse Models of Alzheimer’s Disease

2021 ◽  
Vol 22 (14) ◽  
pp. 7451
Author(s):  
Harpreet Kaur ◽  
Drew Seeger ◽  
Svetlana Golovko ◽  
Mikhail Golovko ◽  
Colin Kelly Combs
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Bile Acid ◽  
Bile Acids ◽  
Cholesterol Metabolism ◽  
Amyloid Β ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Liver Cholesterol ◽  
Bile Acid Metabolism

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive cognitive impairment. It is hypothesized to develop due to the dysfunction of two major proteins, amyloid-β (Aβ) and microtubule-associated protein, tau. Evidence supports the involvement of cholesterol changes in both the generation and deposition of Aβ. This study was performed to better understand the role of liver cholesterol and bile acid metabolism in the pathophysiology of AD. We used male and female wild-type control (C57BL/6J) mice to compare to two well-characterized amyloidosis models of AD, APP/PS1, and AppNL-G-F. Both conjugated and unconjugated primary and secondary bile acids were quantified using UPLC-MS/MS from livers of control and AD mice. We also measured cholesterol and its metabolites and identified changes in levels of proteins associated with bile acid synthesis and signaling. We observed sex differences in liver cholesterol levels accompanied by differences in levels of synthesis intermediates and conjugated and unconjugated liver primary bile acids in both APP/PS1 and AppNL-G-F mice when compared to controls. Our data revealed fundamental deficiencies in cholesterol metabolism and bile acid synthesis in the livers of two different AD mouse lines. These findings strengthen the involvement of liver metabolism in the pathophysiology of AD.

scholarly journals Role of Baicalin and Liver X Receptor Alpha in the Formation of Cholesterol Gallstones in Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Geng Chen ◽  
Shuodong Wu
Keyword(s):  
Oxidative Stress ◽  
Bile Acid ◽  
Cholesterol Metabolism ◽  
Density Lipoprotein ◽  
Liver X Receptor ◽  
Cholesterol Gallstones ◽  
Receptor Alpha ◽  
Lithogenic Diet ◽  
Liver X Receptor Alpha ◽  
And Oxidative Stress

This study was aimed at investigating the effect of baicalin on experimental cholesterol gallstones in mice. The mouse gallstone model was induced by feeding with a lithogenic diet, and cholesterol stones were found in the gallbladder. The lithogenic diet caused elevation of triglycerides, cholesterol, and low-density lipoprotein concentrations and descent of high-density lipoprotein concentration in serum. Hyperplasia and inflammatory infiltration were observed in the gallbladder wall of lithogenic diet-fed mice. We also found the increase of cholesterol content and the decrease of bile acid in bile. Real-time PCR and western blot results demonstrated that the expression levels of two enzymes (cholesterol 7α-hydroxylase (CYP7a1) and sterol 12α-hydroxylase (CYP8b1)) to catalyze the synthesis of bile acid from cholesterol were decreased and that two cholesterol transporters (ATP-binding cassette transporter G5/G8 (ABCG5/8)) were increased in the liver of lithogenic diet-fed mice. The lithogenic diet also led to enhanced activity of alanine aminotransferase and aspartate aminotransferase in serum; increased concentrations of tumor necrosis factor-α, interleukin- (IL-) 1β, IL-6, and malondialdehyde; and decreased superoxide dismutase activity in the liver, suggesting inflammatory and oxidative stress. In addition, liver X receptor alpha (LXRα) was increased in the liver. After gavage of baicalin, the lithogenic diet-induced gallstones, hyperlipidemia, gallbladder hyperplasia, inflammation, and oxidative stress in liver and cholesterol metabolism disorders were all alleviated to some degree. The expression of LXRα in the liver was inhibited by baicalin. In addition, the LXRα agonist T0901317 aggravated lithogenic diet-induced harmful symptoms in mice, including the increase of gallstone formation, hyperlipidemia, hepatic injury, inflammation, and oxidative stress. In conclusion, we demonstrated that baicalin played a protective role in a lithogenic diet-induced gallstone mouse model, which may be mediated by inhibition of LXRα activity. These findings may provide novel insights for prevention and therapy of gallstones in the clinic.

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