ArticleJournal of lipid research2013
Differential regulation of bile acid and cholesterol metabolism by the farnesoid X receptor in Ldlr -/- mice versus hamsters.
Article in Journal of lipid research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 41 citations in OpenAlex.
- German Chamomile (Matricaria chamomilla) Induces Cytochrome P450 Expression Through Increased BMAL1 Protein Expression in Liver Nuclei.Biochemical genetics · 2026Article
- Bile Acids and Type 2 Diabetes: Roles in Glucose Homeostasis and Therapeutic Opportunities.Metabolites · 2025Review
- Gut microbiota-derived metabolites tune host homeostasis fate.Seminars in immunopathology · 2024Review
- Bile acid metabolism and signaling in health and disease: molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2024Review
- Acute Cholesterol-Lowering Effect of Exendin-4 in LdlrJournal of atherosclerosis and thrombosis · 2023Article
- Survival Benefit of Statin with Anti-Angiogenesis Efficacy in Lung Cancer-Associated Pleural Fluid through FXR Modulation.Cancers · 2022Article
- Exposure to a mixture of legacy, alternative, and replacement per- and polyfluoroalkyl substances (PFAS) results in sex-dependent modulation of cholesterol metabolism and liver injury.Environment international · 2021Article
- Isomaltulose Exhibits Prebiotic Activity, and Modulates Gut Microbiota, the Production of Short Chain Fatty Acids, and Secondary Bile Acids in Rats.Molecules (Basel, Switzerland) · 2021Article
- Total flavonoids ofEvidence-based complementary and alternative medicine : eCAM · 2021Article
- Cholesterol metabolism in mice models of genetic hypercholesterolemia.Journal of physiology and biochemistry · 2020Article
- Ablation of gut microbiota alleviates obesity-induced hepatic steatosis and glucose intolerance by modulating bile acid metabolism in hamsters.Acta pharmaceutica Sinica. B · 2019Article
- Emodin Rescues Intrahepatic Cholestasis via Stimulating FXR/BSEP Pathway in Promoting the Canalicular Export of Accumulated Bile.Frontiers in pharmacology · 2019Article
- Farnesoid X Receptor Activation by Obeticholic Acid Elevates Liver Low-Density Lipoprotein Receptor Expression by mRNA Stabilization and Reduces Plasma Low-Density Lipoprotein Cholesterol in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2018Article
- FXR activation by obeticholic acid or nonsteroidal agonists induces a human-like lipoprotein cholesterol change in mice with humanized chimeric liver.Journal of lipid research · 2018Article
- Regulation of lipid metabolism by obeticholic acid in hyperlipidemic hamsters.Journal of lipid research · 2017Article
- Bile acids at the cross-roads of gut microbiome-host cardiometabolic interactions.Diabetology & metabolic syndrome · 2017Review
- Farnesoid X receptor activation increases reverse cholesterol transport by modulating bile acid composition and cholesterol absorption in mice.Hepatology (Baltimore, Md.) · 2016Article
- Role of Inflammatory and Oxidative Stress, Cytochrome P450 2E1, and Bile Acid Disturbance in Rat Liver Injury Induced by Isoniazid and Lipopolysaccharide Cotreatment.Antimicrobial agents and chemotherapy · 2016Article
- Metabolic effects of intestinal absorption and enterohepatic cycling of bile acids.Acta pharmaceutica Sinica. B · 2015Review
- Genome-wide binding and transcriptome analysis of human farnesoid X receptor in primary human hepatocytes.PloS one · 2014Article
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Modulating bile acid synthesis has long been considered a good strategy by which to improve cholesterol homeostasis in humans. The farnesoid X receptor (FXR), the key regulator of bile acid synthesis, was, therefore, identified as an interesting target for drug discovery. We compared the effect of four, structurally unrelated, synthetic FXR agonists in two fat-fed rodent species and observed that the three most potent and selective agonists decreased plasma cholesterol in LDL receptor-deficient (Ldlr (-/-)) mice, but none did so in hamsters. Detailed investigation revealed increases in the expression of small heterodimer partner (Shp) in their livers and of intestinal fibroblast growth factor 15 or 19 (Fgf15/19) in mice only. Cyp7a1 expression and fecal bile acid (BA) excretion were strongly reduced in mice and hamsters by all four FXR agonists, whereas bile acid pool sizes were reduced in both species by all but the X-Ceptor compound in hamsters. In Ldlr (-/-) mice, the predominant bile acid changed from cholate to the more hydrophilic β-muricholate due to a strong repression of Cyp8b1 and increase in Cyp3a11 expression. However, FXR agonists caused only minor changes in the expression of Cyp8b1 and in bile acid profiles in hamsters. In summary, FXR agonist-induced decreases in bile acid pool size and lipophilicity and in cholesterol absorption and synthesis could explain the decreased plasma cholesterol in Ldlr (-/-) mice. In hamsters, FXR agonists reduced bile acid pool size to a smaller extent with minor changes in bile acid profile and reductions in sterol absorption, and consequently, plasma cholesterol was unchanged.
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