Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact

Citations to this article

Farnesoid X receptor represses hepatic human APOA gene expression
Indumathi Chennamsetty, … , Michael Trauner, Gert M. Kostner
Indumathi Chennamsetty, … , Michael Trauner, Gert M. Kostner
Published August 1, 2011
Citation Information: J Clin Invest. 2011;121(9):3724-3734. https://doi.org/10.1172/JCI45277.
View: Text | PDF
Research Article Genetics Article has an altmetric score of 6

Farnesoid X receptor represses hepatic human APOA gene expression

  • Text
  • PDF
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.

Authors

Indumathi Chennamsetty, Thierry Claudel, Karam M. Kostner, Anna Baghdasaryan, Dagmar Kratky, Sanja Levak-Frank, Sasa Frank, Frank J. Gonzalez, Michael Trauner, Gert M. Kostner

×

Total citations by year

Year: 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 Total
Citations: 2 1 7 2 3 2 1 4 4 4 4 1 4 39
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article (39)

Title and authors Publication Year
Comparative Analysis of Atherogenic Lipoproteins L5 and Lp(a) in Atherosclerotic Cardiovascular Disease.
Akyol O, Yang CY, Woodside DG, Chiang HH, Chen CH, Gotto AM
Current Atherosclerosis Reports 2024
Lipoprotein(a) and cardiovascular disease.
Boffa MB, Koschinsky ML
The Biochemical journal 2024
Calcific aortic valve disease: mechanisms, prevention and treatment.
Moncla LM, Briend M, Bossé Y, Mathieu P
Nature reviews. Cardiology 2023
Transcriptional Control of Trpm6 by the Nuclear Receptor FXR
E Kim, J Lee
International journal of molecular sciences 2022
Lp(a) and the Risk for Cardiovascular Disease: Focus on the Lp(a) Paradox in Diabetes Mellitus
Kostner KM, Kostner GM
International journal of molecular sciences 2022
Genome-Wide Characterization of a Highly Penetrant Form of Hyperlipoprotein(a)emia Associated With Genetically Elevated Cardiovascular Risk.
Coassin S, Chemello K, Khantalin I, Forer L, Döttelmayer P, Schönherr S, Grüneis R, Chong-Hong-Fong C, Nativel B, Ramin-Mangata S, Gallo A, Roche M, Muelegger B, Gieger C, Peters A, Zschocke J, Marimoutou C, Meilhac O, Lamina C, Kronenberg F, Blanchard V, Lambert G
Circulation. Genomic and precision medicine 2022
Familial Hypercholesterolemia and Elevated Lipoprotein(a): Cascade Testing and Other Implications for Contextual Models of Care
Loh WJ, Chan DC, Mata P, Watts GF
Frontiers in Genetics 2022
Study on the relationship between hormone and Lp(a) in Chinese overweight/obese patients
Chang X, Bian N, Ding X, Li J, An Y, Wang J, Liu J, Wang G
BMC Endocrine Disorders 2022
Dietary supplementation of porcine bile acids improves laying performance, serum lipid metabolism and cecal microbiota in late-phase laying hens.
Yang B, Huang S, Zhao G, Ma Q
2022
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.
Stoll F, Seidel-Glätzer A, Burghaus I, Göring O, Sauter M, Rose P, Daniel V, Haag M, Schwab M, Riffel J, André F, Taylor L, Weiss J, Burhenne J, Cleeves V, Haefeli WE, Blank A
International journal of molecular sciences 2022
Liver macrophages and inflammation in physiology and physiopathology of non‐alcoholic fatty liver disease
R Thibaut, MC Gage, I PinedaTorra, G Chabrier, N Venteclef, F Alzaid
The FEBS journal 2021
Beyond Lipoprotein(a) plasma measurements: Lipoprotein(a) and inflammation
G Reyes-Soffer, M Westerterp
Pharmacological research : the official journal of the Italian Pharmacological Society 2021
Nuclear receptors and transcriptional regulation in non-alcoholic fatty liver disease
Y Xiao, M Kim, MA Lazar
Molecular Metabolism 2020
A genome-wide analysis of DNA methylation identifies a novel association signal for Lp(a) concentrations in the LPA promoter
S Coassin, N Hermann-Kleiter, M Haun, S Wahl, R Wilson, B Paulweber, S Kunze, T Meitinger, K Strauch, A Peters, M Waldenberger, F Kronenberg, C Lamina, DC Crawford
PloS one 2020
Lipoprotein(a) Lowering—From Lipoprotein Apheresis to Antisense Oligonucleotide Approach
MF Greco, CR Sirtori, A Corsini, M Ezhov, T Sampietro, M Ruscica
Journal of Clinical Medicine 2020
Molecular, Population, and Clinical Aspects of Lipoprotein(a): A Bridge Too Far?
NC Ward, KM Kostner, DR Sullivan, P Nestel, GF Watts
Journal of Clinical Medicine 2019
Lipoprotein(a) Change After Sleeve Gastrectomy Is Affected by the Presence of Metabolic Syndrome
S Paredes, M Alves, ML Pereira, O Marques, L Ribeiro
Obesity Surgery 2019
Changes in lipoprotein(a) following bariatric surgery
BX Lin, MC Weiss, M Parikh, JS Berger, EA Fisher, SP Heffron
American Heart Journal 2018
Lipoprotein(a) Mass Levels Increase Significantly According to APOE GenotypeHighlights: An Analysis of 431 239 Patients
PM Moriarty, SA Varvel, PL Gordts, JP McConnell, S Tsimikas
Arteriosclerosis, thrombosis, and vascular biology 2017
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
A Sahebkar, LE Simental-Mendía, GF Watts, MC Serban, M Banach
BMC Medicine 2017
Effect of diet-induced weight loss on lipoprotein(a) levels in obese individuals with and without type 2 diabetes
KA Berk, R Yahya, AJ Verhoeven, J Touw, FP Leijten, EF van Rossum, VL Wester, MA Lips, H Pijl, R Timman, G Erhart, F Kronenberg, JE van Lennep, EJ Sijbrands, MT Mulder
Diabetologia 2017
Diallyl disulphide inhibits apolipoprotein(a) expression in HepG2 cells through the MEK1-ERK1/2-ELK-1 pathway
X Ma, Y Liu, Y Tan, K Qu, X He, H Zhang, Z Wang
Lipids in Health and Disease 2017
Nat1 Deficiency Is Associated with Mitochondrial Dysfunction and Exercise Intolerance in Mice
I Chennamsetty, M Coronado, K Contrepois, MP Keller, I Carcamo-Orive, J Sandin, G Fajardo, AJ Whittle, M Fathzadeh, M Snyder, G Reaven, AD Attie, D Bernstein, T Quertermous, JW Knowles
Cell Reports 2016
Human Genetics and the Causal Role of Lipoprotein(a) for Various Diseases
F Kronenberg
Cardiovascular Drugs and Therapy 2016
Transcriptional coordination of hepatic autophagy by nutrient-sensing nuclear receptor PPARα and FXR
JM Lee
Annals of Pediatric Endocrinology & Metabolism 2016
Lipoprotein (a): a historical appraisal
KM Kostner, GM Kostner
Journal of lipid research 2016
Identification and validation of NAT2 as an insulin sensitivity gene
Joshua Knowles, Weijia Xie, Zhongyang Zhang, Indumathi Chennemsetty, Themistocles Assimes, Jussi Paananen, Ola Hansson, James Pankow, Mark Goodarzi, Ivan Carcamo-Orive, Andrew Morris, Yii-Der I. Chen, Ville-Petteri Makinen, Andrea Ganna, Xiuqing Guo, Anubha Mahajan, Fahim Abbasi, Danielle Greenawalt, Pek Lum, Cliona Molony, Lars Lind, Cecilia Lindgren, Leslie Raffel, Philip S. Tsao, Eric Schadt, Jerome I. Rotter, Alan Sinaiko, Gerald M. Reaven, Xia Yang, Chao A. Hsiung, Leif Groop, Heather Cordell, Markku Laakso, Ke Hao, Erik Ingelsson, Timothy Frayling, Michael Weedon, Mark Walker, Thomas Quertermous
Journal of Clinical Investigation 2015
Metabolic Control
S Herzig
2015
Targeting Lipoprotein (a): an Evolving Therapeutic Landscape
LC Man, E Kelly, D Duffy
Current Atherosclerosis Reports 2015
Serum lipoprotein (a) concentrations are inversely associated with T2D, prediabetes, and insulin resistance in a middle-aged and elderly Chinese population
L Ding, A Song, M Dai, M Xu, W Sun, B Xu, J Sun, T Wang, Y Xu, J Lu, W Wang, Y Bi, G Ning
Journal of lipid research 2015
Nuclear bile acid signaling through the farnesoid X receptor
C Mazuy, A Helleboid, B Staels, P Lefebvre
Cellular and Molecular Life Sciences 2014
Nutrient-sensing nuclear receptors coordinate autophagy
JM Lee, M Wagner, R Xiao, KH Kim, D Feng, MA Lazar, DD Moore
Nature 2014
FGF21 inhibits apolipoprotein(a) expression in HepG2 cells via the FGFR1-ERK1/2-Elk-1 pathway
X Lin, G Li, X He, X Ma, K Zhang, H Zhang, G Zeng, Z Wang
Molecular and Cellular Biochemistry 2014
Relook at lipoprotein (A): independent risk factor of coronary artery disease in north Indian population
J Yusuf, N Yadav, S Mukhopadhyay, A Goyal, V Mehta, V Trehan, S Tyagi
Indian Heart Journal 2014
Update on Lipoprotein(a) as a Cardiovascular Risk Factor and Mediator
MB Boffa, ML Koschinsky
Current Atherosclerosis Reports 2013
Bile acid receptors as targets for the treatment of dyslipidemia and cardiovascular disease
G Porez, J Prawitt, B Gross, B Staels
Journal of lipid research 2012
Lipoprotein(a) metabolism: Potential sites for therapeutic targets
J Hoover-Plow, M Huang
Metabolism 2012
Nicotinic acid inhibits hepatic APOA gene expression: studies in humans and in transgenic mice
I Chennamsetty, KM Kostner, T Claudel, M Vinod, S Frank, TS Weiss, M Trauner, GM Kostner
Journal of lipid research 2012
A Systematic Literature Review of the Association of Lipoprotein(a) and Autoimmune Diseases and Atherosclerosis
I Missala, U Kassner, E Steinhagen-Thiessen
International Journal of Rheumatology 2012

← Previous 1 2 Next →

Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Posted by 4 X users
Referenced in 1 patents
Highlighted by 1 platforms
52 readers on Mendeley
See more details