scholarly journals Molecular Mechanisms Underlying the Link between Nuclear Receptor Function and Cholesterol Gallstone Formation

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Mary Carmen Vázquez ◽  
Attilio Rigotti ◽  
Silvana Zanlungo
Keyword(s):  
Nuclear Receptors ◽  
Nuclear Receptor ◽  
Molecular Mechanisms ◽  
Cholesterol Metabolism ◽  
Cholesterol Gallstone ◽  
Gallstone Disease ◽  
Gallstone Formation ◽  
Receptor Function ◽  
Prevalent Disease ◽  
Bile Cholesterol

Cholesterol gallstone disease is highly prevalent in western countries, particularly in women and some specific ethnic groups. The formation of water-insoluble cholesterol crystals is due to a misbalance between the three major lipids present in the bile: cholesterol, bile salts, and phospholipids. Many proteins implicated in biliary lipid secretion in the liver are regulated by several transcription factors, including nuclear receptors LXR and FXR. Human and murine genetic, physiological, pathophysiological, and pharmacological evidence is consistent with the relevance of these nuclear receptors in gallstone formation. In addition, there is emerging data that also suggests a role for estrogen receptor ESR1 in abnormal cholesterol metabolism leading to gallstone disease. A better comprehension of the role of nuclear receptor function in gallstone formation may help to design new and more effective therapeutic strategies for this highly prevalent disease condition.

scholarly journals Gut microbiota promotes cholesterol gallstone formation by modulating bile acid composition and biliary cholesterol secretion

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Hai Hu ◽  
Wentao Shao ◽  
Qian Liu ◽  
Ning Liu ◽  
Qihan Wang ◽  
...  
Keyword(s):  
Bile Acid ◽  
Gut Microbiota ◽  
Cholesterol Metabolism ◽  
Cholesterol Gallstone ◽  
Gallstone Disease ◽  
Gallstone Formation ◽  
Common Disease ◽  
Intestinal Cholesterol Absorption ◽  
Fecal Transplantation ◽  
Hepatic Expression

AbstractCholesterol gallstone disease is a worldwide common disease. Cholesterol supersaturation in gallbladder bile is the prerequisite for its pathogenesis, while the mechanism is not completely understood. In this study, we find enrichment of gut microbiota (especially Desulfovibrionales) in patients with gallstone disease. Fecal transplantation of gut microbiota from gallstone patients to gallstone-resistant strain of mice can induce gallstone formation. Carrying Desulfovibrionales is associated with enhanced cecal secondary bile acids production and increase of bile acid hydrophobicity facilitating intestinal cholesterol absorption. Meanwhile, the metabolic product of Desulfovibrionales, H2S increase and is shown to induce hepatic FXR and inhibit CYP7A1 expression. Mice carrying Desulfovibrionales present induction of hepatic expression of cholesterol transporters Abcg5/g8 to promote biliary secretion of cholesterol as well. Our study demonstrates the role of gut microbiota, Desulfovibrionales, as an environmental regulator contributing to gallstone formation through its influence on bile acid and cholesterol metabolism.

scholarly journals Hepatic cholesterol metabolism in cholesterol gallstone disease

1991 ◽  
Vol 32 (3) ◽  
pp. 469-475
Author(s):  
E Reihnér ◽  
B Angelin ◽  
I Björkhem ◽  
K Einarsson
Keyword(s):  
Cholesterol Metabolism ◽  
Cholesterol Gallstone ◽  
Gallstone Disease ◽  
Hepatic Cholesterol

scholarly journals Quantitative trait loci mapping for cholesterol gallstones in AKR/J and C57L/J strains of mice

2000 ◽  
Vol 4 (1) ◽  
pp. 59-65 ◽  
Author(s):  
BEVERLY PAIGEN ◽  
NICHOLAS J. SCHORK ◽  
KAREN L. SVENSON ◽  
YIN-CHAI CHEAH ◽  
JIAN-LONG MU ◽  
...  
Keyword(s):  
Quantitative Trait ◽  
Congenic Strain ◽  
Cholesterol Gallstone ◽  
Gallstone Disease ◽  
Gallstone Formation ◽  
Quantitative Trait Loci Mapping ◽  
Cholesterol Gallstones ◽  
Lithogenic Diet ◽  
The Difference ◽  
Trait Locus

Quantitative trait locus (QTL) mapping was used to locate genes that determine the difference in cholesterol gallstone disease between the gallstone-susceptible strain C57L/J and the gallstone-resistant strain AKR/J. Gallstone weight was determined in 231 male (AKR × C57L) F1× AKR backcross mice fed a lithogenic diet containing 1% cholesterol, 0.5% cholic acid, and 15% butterfat for 8 wk. Mice having no stones and mice having the largest stones were genotyped at ∼20-cM intervals to find the loci determining cholesterol gallstone formation. The major locus, Lith1, mapped near D2Mit56 and was confirmed by constructing a congenic strain, AK.L- Lith1s. Another locus, Lith2, mapped near D19Mit58 and was also confirmed by constructing a congenic strain AK.L- Lith2s. Other suggestive, but not statistically significant, loci mapped to chromosomes 6, 7, 8, 10, and X. The identification of these Lith genes will elucidate the pathophysiology of cholesterol gallstone formation.

scholarly journals The Role of Diet in the Pathogenesis of Cholesterol Gallstones

2019 ◽  
Vol 26 (19) ◽  
pp. 3620-3638 ◽  
Author(s):  
Agostino Di Ciaula ◽  
Gabriella Garruti ◽  
Gema Frühbeck ◽  
Maria De Angelis ◽  
Ornella de Bari ◽  
...  
Keyword(s):  
Vitamin C ◽  
Fast Food ◽  
Cholesterol Gallstone ◽  
Gallstone Disease ◽  
Gallstone Formation ◽  
Protective Role ◽  
Cholesterol Homeostasis ◽  
Major Health Problem ◽  
Cholesterol Gallstones ◽  
Beneficial Effects

: Cholesterol gallstone disease is a major health problem in Westernized countries and depends on a complex interplay between genetic factors, lifestyle and diet, acting on specific pathogenic mechanisms. Overweigh, obesity, dyslipidemia, insulin resistance and altered cholesterol homeostasis have been linked to increased gallstone occurrence, and several studies point to a number of specific nutrients as risk- or protective factors with respect to gallstone formation in humans. There is a rising interest in the identification of common and modifiable dietetic factors that put the patients at risk of gallstones or that are able to prevent gallstone formation and growth. In particular, dietary models characterized by increased energy intake with highly refined sugars and sweet foods, high fructose intake, low fiber contents, high fat, consumption of fast food and low vitamin C intake increase the risk of gallstone formation. On the other hand, high intake of monounsaturated fats and fiber, olive oil and fish (ω-3 fatty acids) consumption, vegetable protein intake, fruit, coffee, moderate alcohol consumption and vitamin C supplementation exert a protective role. : The effect of some confounding factors (e.g., physical activity) cannot be ruled out, but general recommendations about the multiple beneficial effects of diet on cholesterol gallstones must be kept in mind, in particular in groups at high risk of gallstone formation.

[300] HEPATIC EXPRESSION OF NUCLEAR RECEPTORS AND BILIARY TRANSPORTERS IN HUMAN CHOLESTEROL GALLSTONE DISEASE

2007 ◽  
Vol 46 ◽  
pp. S119 ◽  
Author(s):  
M. Bertolotti ◽  
C. Gabbi ◽  
C. Anzivino ◽  
E. Tagliafico ◽  
L. Carulli ◽  
...  
Keyword(s):  
Nuclear Receptors ◽  
Cholesterol Gallstone ◽  
Gallstone Disease ◽  
Hepatic Expression

scholarly journals Protective Effects of Yinchenhao Decoction on Cholesterol Gallstone in Mice Fed a Lithogenic Diet by Regulating LXR, CYP7A1, CYP7B1, and HMGCR Pathways

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Yong Meng ◽  
Ke Meng ◽  
Xin Zhao ◽  
Donghua Li ◽  
Qiaoying Gao ◽  
...  
Keyword(s):  
Cholesterol Gallstone ◽  
Saturation Index ◽  
Gallstone Formation ◽  
Intragastric Administration ◽  
Protective Effects ◽  
Biochemical Tests ◽  
Lithogenic Diet ◽  
Preventive Drug ◽  
Cholesterol Saturation Index ◽  
Bile Cholesterol

The study attempted to elucidate whether lipid genes are closely associated with lipid metabolic abnormalities during the lithogenic time and how Yinchenhao Decoction (YCHD) works on the transcriptions of lipid genes against cholesterol gallstone model. C57BL/6J mice fed on lithogenic diet (LD) were used for model establishment and randomized into 5 groups. All groups received LD for different weeks with isometrically intragastric administration of YCHD or NS. Biochemical tests were measured and liver tissues were harvested for histological and genetic detection. It was found that all groups with increasing LD showed a following tendency of gallstone incidence, bile cholesterol, phospholipids, total bile acid, and cholesterol saturation index (CSI). Conversely, YCHD could significantly normalize the levels of gallstone incidence, bile lipids, and CSI (CSI<1). As lithogenic time progressed, ABCG5, ABCG8, PPAR-α, and ABCB4 were upregulated, and SREBP2, CYP7A1, and CYP7B1 were downregulated, while CYP7A1, CYP7B1, LXR, and HMGCR mRNA were increased 3-fold under the administration of YCHD. It was concluded that abnormal expressions of the mentioned genes may eventually progress to cholesterol gallstone. CYP7A1, CYP7B1, LXR, and HMGCR mRNA may be efficient targets of YCHD, which may be a preventive drug to reverse liver injury, normalize bile lipids, facilitate gallstone dissolution, and attenuate gallstone formation.

scholarly journals Current Views on Genetics and Epigenetics of Cholesterol Gallstone Disease

Cholesterol ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Agostino Di Ciaula ◽  
David Q.-H. Wang ◽  
Leonilde Bonfrate ◽  
Piero Portincasa
Keyword(s):  
Insulin Resistance ◽  
Genetic Factors ◽  
Cholesterol Metabolism ◽  
Cholesterol Gallstone ◽  
Gallstone Disease ◽  
Cholesterol Homeostasis ◽  
Cholesterol Gallstones ◽  
The Metabolic Syndrome ◽  
Digestive Diseases

Cholesterol gallstone disease, one of the commonest digestive diseases in western countries, is induced by an imbalance in cholesterol metabolism, which involves intestinal absorption, hepatic biosynthesis, and biliary output of cholesterol, and its conversion to bile acids. Several components of the metabolic syndrome (e.g., obesity, type 2 diabetes, dyslipidemia, and hyperinsulinemia) are also well-known risk factors for gallstones, suggesting the existence of interplay between common pathophysiological pathways influenced by insulin resistance, genetic, epigenetic, and environmental factors. Cholesterol gallstones may be enhanced, at least in part, by the abnormal expression of a set of the genes that affect cholesterol homeostasis and lead to insulin resistance. Additionally, epigenetic mechanisms (mainly DNA methylation, histone acetylation/deacetylation, and noncoding microRNAs) may modify gene expression in the absence of an altered DNA sequence, in response to different lithogenic environmental stimuli, such as diet, lifestyle, pollutants, also occurring in utero before birth. In this review, we will comment on various steps of the pathogenesis of cholesterol gallstones and interaction between environmental and genetic factors. The epigenomic approach may offer new options for therapy of gallstones and better possibilities for primary prevention in subjects at risk.

scholarly journals An improved method for quantitative ChIP studies of nuclear receptor function

2019 ◽  
Vol 62 (4) ◽  
pp. 169-177
Author(s):  
Ann Louise Hunter ◽  
Natasha Narang ◽  
Matthew Baxter ◽  
David W Ray ◽  
Toryn M Poolman
Keyword(s):  
Nuclear Receptors ◽  
Nuclear Receptor ◽  
Chromatin Immunoprecipitation ◽  
Digital Pcr ◽  
Droplet Digital Pcr ◽  
Correct Interpretation ◽  
Receptor Function ◽  
Improved Method ◽  
Chip Data ◽  
Accurate Quantification

Chromatin immunoprecipitation (ChIP) is a valuable tool for the endocrine researcher, providing a means to measure the recruitment of hormone-activated nuclear receptors, for example. However, the technique can be challenging to perform and has multiple experimental steps, risking introduction of error at each. The data produced can be challenging to interpret; several different methods are commonly used for normalising data and thus comparing between conditions. Absolute, sensitive quantification of protein-bound DNA is important for correct interpretation of the data. In addition, such quantification can help the investigator in troubleshooting experiments. Here, we outline a ChIP strategy combining droplet digital PCR for accurate quantification with an internal spike-in control for normalisation. This combination strengthens the reliability of ChIP data and allows the operator to optimise their protocol with greater confidence.

scholarly journals Nuclear receptor regulation gears up another Notch

2006 ◽  
Vol 4 (1) ◽  
pp. nrs.04001 ◽  
Author(s):  
Borja Belandia ◽  
Malcolm G. Parker
Keyword(s):  
Notch Signaling ◽  
Nuclear Receptors ◽  
Nuclear Receptor ◽  
Molecular Mechanisms ◽  
Receptor Regulation ◽  
Functional Interactions ◽  
Eukaryotic Organisms

In this perspective we describe examples of crosstalk between nuclear receptors (NRs) and Notch signaling by means of direct functional interactions between components of both pathways. This crosstalk may provide eukaryotic organisms with molecular mechanisms for the coordination of llong-distance endocrine signals with cell-to-cell juxtacrine communication.

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