ArticleThe Journal of clinical investigation2011
Farnesoid X receptor represses hepatic human APOA gene expression.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
44 citing papers in PubMed, 2 syntheses or guidelines pooled it, 113 citations in OpenAlex.
- Comparison of the effects of fibrates versus statins on plasma lipoprotein(a) concentrations: a systematic review and meta-analysis of head-to-head randomized controlled trials.BMC medicine · 2017 · on this mapPooled it
- Identification and validation of N-acetyltransferase 2 as an insulin sensitivity gene.The Journal of clinical investigation · 2015Pooled it
- DNA induces non-canonical dimerization of the farnesoid X receptor.Nucleic acids research · 2026Article
- Liver Metabolism at the Crossroads: The Reciprocal Control of Nutrient-Sensing Nuclear Receptors and Autophagy.International journal of molecular sciences · 2025Review
- Lipoprotein(a) and cardiovascular disease.The Biochemical journal · 2024Review
- Comparative Analysis of Atherogenic Lipoproteins L5 and Lp(a) in Atherosclerotic Cardiovascular Disease.Current atherosclerosis reports · 2024Review
- Calcific aortic valve disease: mechanisms, prevention and treatment.Nature reviews. Cardiology · 2023Review
- Metabolic Effect of Blocking Sodium-Taurocholate Co-Transporting Polypeptide in Hypercholesterolemic Humans with a Twelve-Week Course of Bulevirtide-An Exploratory Phase I Clinical Trial.International journal of molecular sciences · 2022Article
- Dietary supplementation of porcine bile acids improves laying performance, serum lipid metabolism and cecal microbiota in late-phase laying hens.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2022Article
- Liver macrophages and inflammation in physiology and physiopathology of non-alcoholic fatty liver disease.The FEBS journal · 2022Review
- Study on the relationship between hormone and Lp(a) in Chinese overweight/obese patients.BMC endocrine disorders · 2022Article
- Genome-Wide Characterization of a Highly Penetrant Form of Hyperlipoprotein(a)emia Associated With Genetically Elevated Cardiovascular Risk.Circulation. Genomic and precision medicine · 2022Article
- Lp(a) and the Risk for Cardiovascular Disease: Focus on the Lp(a) Paradox in Diabetes Mellitus.International journal of molecular sciences · 2022Review
- Transcriptional Control ofInternational journal of molecular sciences · 2022Article
- Familial Hypercholesterolemia and Elevated Lipoprotein(a): Cascade Testing and Other Implications for Contextual Models of Care.Frontiers in genetics · 2022Review
- Nuclear receptors and transcriptional regulation in non-alcoholic fatty liver disease.Molecular metabolism · 2021Review
- Beyond Lipoprotein(a) plasma measurements: Lipoprotein(a) and inflammation.Pharmacological research · 2021Review
- Acute and Chronic Impact of Biliopancreatic Diversion with Duodenal Switch Surgery on Plasma Lipoprotein(a) Levels in Patients with Severe Obesity.Obesity surgery · 2020Article
- Lipoprotein(a) Lowering-From Lipoprotein Apheresis to Antisense Oligonucleotide Approach.Journal of clinical medicine · 2020Review
- Lipoprotein(a) Change After Sleeve Gastrectomy Is Affected by the Presence of Metabolic Syndrome.Obesity surgery · 2020Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
High plasma concentrations of lipoprotein(a) [Lp(a), which is encoded by the APOA gene] increase an individual's risk of developing diseases, such as coronary artery diseases, restenosis, and stroke. Unfortunately, increased Lp(a) levels are minimally influenced by dietary changes or drug treatment. Further, the development of Lp(a)-specific medications has been hampered by limited knowledge of Lp(a) metabolism. In this study, we identified patients suffering from biliary obstructions with very low plasma Lp(a) concentrations that rise substantially after surgical intervention. Consistent with this, common bile duct ligation in mice transgenic for human APOA (tg-APOA mice) lowered plasma concentrations and hepatic expression of APOA. To test whether farnesoid X receptor (FXR), which is activated by bile acids, was responsible for the low plasma Lp(a) levels in cholestatic patients and mice, we treated tg-APOA and tg-APOA/Fxr-/- mice with cholic acid. FXR activation markedly reduced plasma concentrations and hepatic expression of human APOA in tg-APOA mice but not in tg-APOA/Fxr-/- mice. Incubation of primary hepatocytes from tg-APOA mice with bile acids dose dependently downregulated APOA expression. Further analysis determined that the direct repeat 1 element between nucleotides -826 and -814 of the APOA promoter functioned as a negative FXR response element. This motif is also bound by hepatocyte nuclear factor 4α (HNF4α), which promotes APOA transcription, and FXR was shown to compete with HNF4α for binding to this motif. These findings may have important implications in the development of Lp(a)-lowering medications.
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Registered trials
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