Niemann-Pick C1-like 1 is required for an LXR agonist to raise plasma HDL cholesterol in mice

Arteriosclerosis, Thrombosis, and Vascular Biology
Weiqing TangLiqing Yu

Abstract

Activation of liver x receptor (LXR) raises plasma HDL-cholesterol (HDL-C) in mice. Interestingly, the LXR agonist GW3965 fails to raise plasma HDL-C in mice lacking intestinal ABCA1, indicating that intestinal ABCA1 plays a predominant role in GW3965-mediated HDL production. How this is coupled to intestinal function remains elusive. Because cholesterol is essential for HDL assembly and directly regulates intestinal ABCA1 expression via activating LXR, we hypothesized that cholesterol absorption, a major function of intestine, modulates LXR-dependent HDL formation. Mice lacking Niemann-Pick C1-Like 1 (NPC1L1) (L1-KO mice), a gene that is essential for cholesterol absorption, were treated with LXR agonist T0901317 for 7 days. Intriguingly, this treatment failed to significantly raise plasma HDL-C but caused a much greater fecal cholesterol excretion in L1-KO mice. The intestinal ABCA1 mRNA level was about 4-fold lower in L1-KO versus wild-type mice, and increased 3.9-fold and 8.8-fold after T0901317 treatment in wild-type and L1-KO mice, respectively. Hepatic ABCA1 failed to respond to T0901317 in mice of both genotypes, although hepatic mRNAs for many LXR target genes were higher in the T0901317-treated versus untreated wild-t...Continue Reading

References

Oct 1, 1977·Applied and Environmental Microbiology·M R SadzikowskiT D Wilkins
Apr 13, 2000·Proceedings of the National Academy of Sciences of the United States of America·J McNeishO L Francone
Nov 23, 2000·Genes & Development·J R SchultzB Shan
Mar 20, 2002·The Journal of Biological Chemistry·Joyce J RepaDavid J Mangelsdorf
May 29, 2002·Proceedings of the National Academy of Sciences of the United States of America·Sean B JosephPeter Tontonoz
Jul 10, 2002·The Journal of Biological Chemistry·Torsten PlōschFolkert Kuipers
Aug 15, 2002·The Journal of Biological Chemistry·Guoqing CaoXian-Cheng Jiang
Nov 22, 2002·Proceedings of the National Academy of Sciences of the United States of America·Liqing YuHelen H Hobbs
Feb 21, 2004·Science·Scott W AltmannMichael P Graziano
May 1, 2004·Proceedings of the National Academy of Sciences of the United States of America·Kara N Maxwell, Jan L Breslow
Jan 27, 2005·The Journal of Biological Chemistry·Joanna P DaviesYiannis A Ioannou
Sep 10, 2005·Journal of Lipid Research·Ryan E TemelLawrence L Rudel
Mar 18, 2006·The Journal of Clinical Investigation·Liam R BrunhamMichael R Hayden
Oct 31, 2006·World Journal of Gastroenterology : WJG·Janine-K KruitFolkert Kuipers
Jun 26, 2007·Journal of Atherosclerosis and Thrombosis·Harry R Davis, Enrico P Veltri
Jul 23, 2008·Perspectives in Vascular Surgery and Endovascular Therapy·Kimon Bekelis, Nicos Labropoulos

❮ Previous
Next ❯

Citations

Jan 23, 2009·American Journal of Physiology. Endocrinology and Metabolism·Jahangir Iqbal, M Mahmood Hussain
Jul 20, 2012·Physiological Reviews·Nada A Abumrad, Nicholas O Davidson
Aug 20, 2008·Journal of Lipid Research·F Jeffrey FieldSatya N Mathur
Jan 15, 2009·Journal of Lipid Research·Ryan E TemelLiqing Yu
Jul 2, 2008·Internal Medicine·Shin-ichiro Miura, Keijiro Saku
Aug 13, 2009·Journal of Atherosclerosis and Thrombosis·Atsushi NoharaHiroshi Mabuchi
Sep 3, 2010·Annual Review of Physiology·Lin JiaLiqing Yu
Jul 10, 2008·Expert Opinion on Drug Metabolism & Toxicology·Minna T JänisMatej Oresic
Nov 13, 2009·Clinical Pharmacology and Therapeutics·J L Betters, L Yu
Sep 18, 2008·Journal of Lipid Research·Weiqing TangLiqing Yu
Jul 30, 2014·Journal of Lipid Research·Chiara DegirolamoAntonio Moschetta
Mar 31, 2018·Arteriosclerosis, Thrombosis, and Vascular Biology·Kristin L BowdenGordon A Francis
Nov 28, 2008·Cardiovascular Therapeutics·Jerzy Bełtowski
May 23, 2012·Evidence-based Complementary and Alternative Medicine : ECAM·Wei-Jian BeiYang Cao
Oct 12, 2010·Clinica Chimica Acta; International Journal of Clinical Chemistry·V S NunesE C R Quintão
Jan 12, 2010·Clinica Chimica Acta; International Journal of Clinical Chemistry·Yan-Wei HuQian Wang
Apr 7, 2010·Progress in Lipid Research·Maaike H OosterveerFolkert Kuipers

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.