scholarly journals Liver-Specific β-Catenin Knockout Mice Exhibit Defective Bile Acid and Cholesterol Homeostasis and Increased Susceptibility to Diet-Induced Steatohepatitis

2010 ◽  
Vol 176 (2) ◽  
pp. 744-753 ◽  
Author(s):  
Jaideep Behari ◽  
Tzu-Hsuan Yeh ◽  
Lindsay Krauland ◽  
Wade Otruba ◽  
Benjamin Cieply ◽  
...  
Keyword(s):  
Bile Acid ◽  
Knockout Mice ◽  
Cholesterol Homeostasis ◽  
Increased Susceptibility

scholarly journals Regulation of Bile Acid and Cholesterol Metabolism by PPARs

PPAR Research ◽  
2009 ◽  
Vol 2009 ◽  
pp. 1-15 ◽  
Author(s):  
Tiangang Li ◽  
John Y. L. Chiang
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Cholesterol Metabolism ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Cholesterol Homeostasis ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Major Pathway ◽  
Therapeutic Implications

Bile acids are amphipathic molecules synthesized from cholesterol in the liver. Bile acid synthesis is a major pathway for hepatic cholesterol catabolism. Bile acid synthesis generates bile flow which is important for biliary secretion of free cholesterol, endogenous metabolites, and xenobiotics. Bile acids are biological detergents that facilitate intestinal absorption of lipids and fat-soluble vitamins. Recent studies suggest that bile acids are important metabolic regulators of lipid, glucose, and energy homeostasis. Agonists of peroxisome proliferator-activated receptors (PPARα, PPARγ, PPARδ) regulate lipoprotein metabolism, fatty acid oxidation, glucose homeostasis and inflammation, and therefore are used as anti-diabetic drugs for treatment of dyslipidemia and insulin insistence. Recent studies have shown that activation of PPARαalters bile acid synthesis, conjugation, and transport, and also cholesterol synthesis, absorption and reverse cholesterol transport. This review will focus on the roles of PPARs in the regulation of pathways in bile acid and cholesterol homeostasis, and the therapeutic implications of using PPAR agonists for the treatment of metabolic syndrome.

scholarly journals Mechanisms of cholesterol-lowering effects of dietary insoluble fibres: relationships with intestinal and hepatic cholesterol parameters

2005 ◽  
Vol 94 (3) ◽  
pp. 331-337 ◽  
Author(s):  
Ariëtte M. van Bennekum ◽  
David V. Nguyen ◽  
Georg Schulthess ◽  
Helmut Hauser ◽  
Michael C. Phillips
Keyword(s):  
Bile Acid ◽  
Food Intake ◽  
Serum Cholesterol ◽  
Cholesterol Absorption ◽  
Cholesterol Homeostasis ◽  
Hepatic Cholesterol ◽  
Intestinal Cholesterol Absorption ◽  
Cholesterol Lowering ◽  
Dietary Fibres ◽  
Bile Acid Binding

Fibres with a range of abilities to perturb cholesterol homeostasis were used to investigate how the serum cholesterol-lowering effects of insoluble dietary fibres are related to parameters of intestinal cholesterol absorption and hepatic cholesterol homeostasis in mice. Cholestyramine, chitosan and cellulose were used as examples of fibres with high, intermediate and low bile acid-binding capacities, respectively. The serum cholesterol levels in a control group of mice fed a high fat/high cholesterol (HFHC) diet for 3 weeks increased about 2-fold to 4·3 mm and inclusion of any of these fibres at 7·5 % of the diet prevented this increase from occurring. In addition, the amount of cholesterol accumulated in hepatic stores due to the HFHC diet was reduced by treatment with these fibres. The three kinds of fibres showed similar hypocholesterolaemic activity; however, cholesterol depletion of liver tissue was greatest with cholestyramine. The mechanisms underlying the cholesterol-lowering effect of cholestyramine were (1) decreased cholesterol (food) intake, (2) decreased cholesterol absorption efficiency, and (3) increased faecal bile acid and cholesterol excretion. The latter effects can be attributed to the high bile acid-binding capacity of cholestyramine. In contrast, incorporation of chitosan or cellulose in the diet reduced cholesterol (food) intake, but did not affect either intestinal cholesterol absorption or faecal sterol output. The present study provides strong evidence that above all satiation and satiety effects underlie the cholesterol-lowering properties of insoluble dietary fibres with moderate or low bile acid-binding capabilities.

Overexpression of CYP27 in hepatic and extrahepatic cells: role in the regulation of cholesterol homeostasis

2001 ◽  
Vol 281 (1) ◽  
pp. G293-G301 ◽  
Author(s):  
E. Hall ◽  
P. Hylemon ◽  
Z. Vlahcevic ◽  
D. Mallonee ◽  
K. Valerie ◽  
...  
Keyword(s):  
Bile Acid ◽  
Cho Cells ◽  
Specific Activity ◽  
Recombinant Adenovirus ◽  
Cholesterol Acyltransferase ◽  
Chinese Hamster ◽  
Cholesterol Homeostasis ◽  
Hep G2 ◽  
Hep G2 Cells ◽  
G2 Cells

In the liver, sterol 27-hydroxylase (CYP27) participates in the classic and alternative pathways of bile acid biosynthesis from cholesterol (Chol). In extrahepatic tissues, CYP27 converts intracellular Chol to 27-hydroxycholesterol (27OH-Chol), which may regulate the activity of 3-hydroxy-3-methylglutaryl CoA reductase (HMG-CoA-R). This study attempts to better define the role of CYP27 in the maintenance of Chol homeostasis in hepatic and extrahepatic cells by overexpressing CYP27 in Hep G2 cells and Chinese hamster ovary (CHO) cells through infection with a replication-defective recombinant adenovirus encoding for CMV-CYP27. After infection, CYP27 mRNA and protein levels increased dramatically. CYP27 specific activity also increased two- to fourfold in infected cells ( P ≤ 0.02), with a marked increase in conversion of [14C]Chol to [14C]27OH-Chol (∼150%; P ≤ 0.01). Accumulation of 27OH-Chol in CHO cells was associated with a 50% decrease in HMG-CoA-R specific activity ( P ≤ 0.02). In infected Hep G2 cells, the significant increase in bile acid synthesis (46%; P ≤ 0.006), which prevented the accumulation of intracellular 27OH-Chol, resulted in increased HMG-CoA-R activity (183%; P ≤ 0.02). Overexpression of CYP27 in Hep G2 cells also increased acyl CoA-cholesterol acyltransferase (71%, P ≤ 0.02) and decreased cholesteryl ester hydrolase (55%, P ≤ 0.02). In conclusion, CYP27 generates different physiological responses depending on cell type and presence or absence of bile acid biosynthetic pathways.

P1194 : Delayed bile acid uptake with metabolic consequences in NA+-taurocholate cotransporting polypeptide knockout mice

2015 ◽  
Vol 62 ◽  
pp. S803
Author(s):  
D. Slijepcevic ◽  
J.M. Donkers ◽  
C. Kaufman ◽  
C.G.K. Wichers ◽  
E.H. Gilglioni ◽  
...  
Keyword(s):  
Bile Acid ◽  
Knockout Mice ◽  
Acid Uptake ◽  
Bile Acid Uptake

III. Bile acids and nuclear receptors

2003 ◽  
Vol 284 (3) ◽  
pp. G349-G356 ◽  
Author(s):  
John Y. L. Chiang
Keyword(s):  
Bile Acid ◽  
Cardiovascular Diseases ◽  
Bile Acids ◽  
Nuclear Receptors ◽  
Molecular Mechanisms ◽  
Genetic Manipulation ◽  
Regulatory Genes ◽  
Cholesterol Homeostasis ◽  
Physiological Pathways ◽  
Bile Acid Receptor

Bile acids are physiological detergents that facilitate excretion, absorption, and transport of fats and sterols in the intestine and liver. Recent studies reveal that bile acids also are signaling molecules that activate several nuclear receptors and regulate many physiological pathways and processes to maintain bile acid and cholesterol homeostasis. Mutations of the principal regulatory genes in bile acid biosynthetic pathways have recently been identified in human patients with hepatobiliary and cardiovascular diseases. Genetic manipulation of key regulatory genes and bile acid receptor genes in mice have been obtained. These advances have greatly improved our understanding of the molecular mechanisms underlying complex liver physiology but also raise many questions and controversies to be resolved. These developments will lead to early diagnosis and discovery of drugs for treatment of liver and cardiovascular diseases.

scholarly journals Changes in Mucosal Homeostasis Predispose NHE3 Knockout Mice to Increased Susceptibility to DSS-Induced Epithelial Injury

2009 ◽  
Vol 137 (3) ◽  
pp. 965-975.e10 ◽  
Author(s):  
Pawel R. Kiela ◽  
Daniel Laubitz ◽  
Claire B. Larmonier ◽  
Monica T. Midura–Kiela ◽  
Maciej A. Lipko ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Epithelial Injury ◽  
Mucosal Homeostasis ◽  
Increased Susceptibility

scholarly journals Increased Susceptibility to Pulmonary Pseudomonas Infection in Splunc1 Knockout Mice

2013 ◽  
Vol 191 (8) ◽  
pp. 4259-4268 ◽  
Author(s):  
Yanyan Liu ◽  
Marissa E. Di ◽  
Hong Wei Chu ◽  
Xinyu Liu ◽  
Ling Wang ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Pseudomonas Infection ◽  
Increased Susceptibility
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