Cholesterol is converted into dozens of primary and secondary bile acids through pathways subject to negative feedback regulation mediated by the nuclear receptor farnesoid X receptor (FXR) and other effectors. Disruption of the sterol 12alpha-hydroxylase gene (Cyp8b1) in mice prevents the synthesis of cholate, a primary bile acid, and its metabolites. Feedback regulation of the rate-limiting biosynthetic enzyme cholesterol 7alpha-hydroxylase (CYP7A1) is lost in Cyp8b1(-/-) mice, causing expansion of the bile acid pool and alterations in cholesterol metabolism. Expression of other FXR target genes is unaltered in these mice. Cholate restores CYP7A1 regulation in vivo and in vitro. The results implicate cholate as an important negative regulator of bile acid synthesis and provide preliminary evidence for ligand-specific gene activation by a nuclear receptor.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC150802 | PMC |
| http://dx.doi.org/10.1172/JCI16309 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Rapid visual detection of hepatitis E virus combining reverse transcription recombinase-aided amplification with lateral flow dipstick and real-time fluorescence.
J Clin Microbiol
January 2025
Laboratory of Animal Pathology and Public Health, National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing, China.
Unlabelled: Hepatitis E virus (HEV) is a globally prevalent zoonotic pathogen that is primarily spread through the fecal-oral route, such as by consuming undercooked or contaminated pork. HEV infection leads to an estimated 3.3 million symptomatic cases of viral hepatitis and 70,000 deaths in human populations each year.
View Article and Find Full Text PDFcolonization is not mediated by bile salts and utilizes Stickland fermentation of proline in an model.
mSphere
January 2025
Department of Food Science and Technology and Nebraska Food for Health Center, University of Nebraska-Lincoln, Lincoln, Nebraska, USA.
Treatment with antibiotics is a major risk factor for infection, likely due to depletion of the gastrointestinal microbiota. Two microbiota-mediated mechanisms thought to limit colonization include the conversion of conjugated primary bile salts into secondary bile salts toxic to growth and competition between the microbiota and for limiting nutrients. Using a continuous flow model that simulates the nutrient conditions of the distal colon, we investigated how treatment with 6 clinically used antibiotics influenced susceptibility to infection in 12 different microbial communities cultivated from healthy individuals.
View Article and Find Full Text PDFThe impact of a humanized bile acid composition on atherosclerosis development in hypercholesterolaemic Cyp2c70 knockout mice.
Sci Rep
January 2025
Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Bile acids (BAs) play important roles in the context of lipid homeostasis and inflammation. Based on extensive preclinical mouse studies, BA signaling pathways have been implicated as therapeutic targets for cardiovascular diseases. However, differences in BA metabolism between mice and humans hamper translation of preclinical outcomes.
View Article and Find Full Text PDFHigh leafy and root vegetables and high rice dietary patterns were associated with primary and secondary bile acid levels in the feces.
Sci Rep
January 2025
Department of Health and Nutrition, Yamagata Prefectural Yonezawa University of Nutrition Sciences, 6-15-1, Torimachi, Yonezawa, Yamagata, 992-0025, Japan.
Colorectal cancer has the second highest mortality among cancer sites worldwide, with increasing morbidity, high recurrence rates, and even poorer postoperative quality of life. Therefore, preventive strategies for colorectal cancer should be established. This study aimed to cross-sectionally explore dietary patterns affecting the intestinal metabolism of bile acids (BAs), a risk factor for colorectal cancer, in young Japanese women.
View Article and Find Full Text PDFStructural characteristics of a heteropolysaccharide from Ganoderma lucidum and its protective effect against Alzheimer's disease via modulating the microbiota-gut-metabolomics.
Int J Biol Macromol
January 2025
College of Medicine, Jiaxing University, Jiaxing 314001, PR China. Electronic address:
Ganoderma lucidum is a traditional Chinese medicine used to treat Alzheimer's disease (AD), whose main active ingredient is polysaccharides. A heteropolysaccharide named GLPZ-1 was isolated from Ganoderma lucidum. GLPZ-1 (6.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!