Oxysterol generation and liver X receptor-dependent reverse cholesterol transport: Not all roads lead to Rome

2013 ◽  
Vol 368 (1-2) ◽  
pp. 99-107 ◽  
Author(s):  
Parveer S. Pannu ◽  
Sima Allahverdian ◽  
Gordon A. Francis
Keyword(s):  
Reverse Cholesterol Transport ◽  
Liver X Receptor ◽  
Cholesterol Transport

scholarly journals Liver X receptor activation promotes macrophage-to-feces reverse cholesterol transport in a dyslipidemic hamster model

2009 ◽  
Vol 51 (4) ◽  
pp. 763-770 ◽  
Author(s):  
François Briand ◽  
Morgan Tréguier ◽  
Agnès André ◽  
Didier Grillot ◽  
Marc Issandou ◽  
...  
Keyword(s):  
Reverse Cholesterol Transport ◽  
Receptor Activation ◽  
Liver X Receptor ◽  
Cholesterol Transport ◽  
Hamster Model

scholarly journals Tissue-Specific Liver X Receptor Activation Promotes Macrophage Reverse Cholesterol Transport In Vivo

2010 ◽  
Vol 30 (4) ◽  
pp. 781-786 ◽  
Author(s):  
Tomoyuki Yasuda ◽  
Didier Grillot ◽  
Jeffery T. Billheimer ◽  
François Briand ◽  
Philippe Delerive ◽  
...  
Keyword(s):  
Reverse Cholesterol Transport ◽  
Receptor Activation ◽  
Liver X Receptor ◽  
Cholesterol Transport ◽  
Tissue Specific

scholarly journals Cholestenoic Acid Is a Naturally Occurring Ligand for Liver X Receptor α**This work was supported by NIH grants.

Endocrinology ◽  
2000 ◽  
Vol 141 (11) ◽  
pp. 4180-4184 ◽  
Author(s):  
Ching Song ◽  
Shutsung Liao
Keyword(s):  
Lipid Metabolism ◽  
Nuclear Receptor ◽  
Reverse Cholesterol Transport ◽  
Liver X Receptor ◽  
Cholesterol Transport ◽  
Nuclear Receptor Coactivator ◽  
Naturally Occurring ◽  
Liver X Receptor Α ◽  
Cholestenoic Acid ◽  
Neutral Sterols

Abstract Excessive cholesterol is eliminated from extrahepatic cells by reverse cholesterol transport, a process by which neutral sterols are transferred to extracellular acceptor lipoproteins for further transport to the liver. Another process independent of lipoproteins involves excretion of 3β-hydroxy-5-cholesten-25(R)-26-carboxylic (cholestenoic) acid, a metabolite of 27-hydroxycholesterol. Physiological concentrations of cholestenoic acid activated the nuclear receptor liver X receptor α (LXRα; NR1H3), but not other oxysterol receptors. As a ligand, cholestenoic acid modulated interaction of LXRα with the nuclear receptor coactivator Grip-1. Cholestenoic acid, therefore, may function as a signaling molecule for regulation of lipid metabolism via LXRα.

LXR (liver X receptor) and HNF-4 (hepatocyte nuclear factor-4): key regulators in reverse cholesterol transport

2004 ◽  
Vol 32 (1) ◽  
pp. 92-96 ◽  
Author(s):  
M. Crestani ◽  
E. De Fabiani ◽  
D. Caruso ◽  
N. Mitro ◽  
F. Gilardi ◽  
...  
Keyword(s):  
Bile Acid ◽  
Nuclear Receptors ◽  
Reverse Cholesterol Transport ◽  
Liver X Receptor ◽  
Farnesoid X Receptor ◽  
New Drugs ◽  
Fine Tuning ◽  
Cholesterol Transport ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor

Cholesterol homoeostasis is the result of the fine tuning between intake and disposal of this molecule. High levels of cholesterol in the blood are detrimental as they may lead to excessive accumulation in vessel walls, a condition predisposing to the development of atherosclerotic lesions. Cholesterol is removed from the vessel wall and transported to the liver through a process called reverse cholesterol transport. Nuclear receptors are among the most important transcription factors regulating genes involved in different steps of reverse cholesterol transport. Here, we discuss the role of the nuclear receptors LXR (liver X receptor) and HNF-4α (hepatocyte nuclear factor-4α) in different steps of reverse cholesterol transport. LXR controls the transcription of crucial genes in cholesterol efflux from macrophages and its transport to the liver, such as ABCA1 (ATP binding cassette A1), CYP27A1 (sterol 27-hydroxylase), CLA-1 (scavenger receptor type B1) and apolipoprotein E. Some oxysterols present in oxidized low-density lipoproteins and proinflammatory cytokines modulate the activity of LXR by antagonizing the effect of activators of this receptor, thus contributing to cholesterol accumulation in macrophages. Bile acid synthesis, which represents the final step of reverse cholesterol transport, is transcriptionally regulated by several nuclear receptors at the level of the liver-specific cytochrome P450 cholesterol 7α-hydroxylase (CYP7A1), the rate-limiting enzyme of this metabolic pathway. Bile acids returning to the liver through the enterohepatic circulation down-regulate CYP7A1 transcription via the bile acid sensors farnesoid X receptor and HNF-4α. Based on this evidence, these nuclear receptors are candidate targets of new drugs for the treatment and prevention of atherosclerotic disease.

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