Liver X receptor: Difference between revisions

From WikiMD's Wellness Encyclopedia

CSV import
CSV import
 
Line 1: Line 1:
== Liver X Receptor ==
= Liver X Receptor =


The '''Liver X Receptor''' (LXR) is a type of [[nuclear receptor]] that plays a crucial role in the regulation of [[cholesterol]], [[fatty acid]], and [[glucose]] homeostasis. LXRs are activated by [[oxysterols]], which are oxidized derivatives of cholesterol. There are two isoforms of LXR: LXR_ (NR1H3) and LXR_ (NR1H2), which are encoded by separate genes and have distinct tissue distribution and functions.
[[File:LXRα-RXR_whole_structure.png|thumb|right|300px|Structure of the LXRα-RXR complex.]]


=== Structure and Function ===
The '''Liver X Receptor''' (LXR) is a type of [[nuclear receptor]] that functions as a [[transcription factor]] regulating the expression of genes involved in [[cholesterol]], [[fatty acid]], and [[glucose metabolism]]. LXRs are activated by [[oxysterols]], which are oxidized derivatives of [[cholesterol]].


Liver X Receptors are part of the nuclear receptor superfamily, which includes receptors for steroid hormones, thyroid hormones, and other lipophilic substances. LXRs function as transcription factors that regulate the expression of genes involved in lipid metabolism. Upon activation by their ligands, LXRs form heterodimers with the [[retinoid X receptor]] (RXR) and bind to specific DNA sequences known as LXR response elements (LXREs) in the promoter regions of target genes.
== Types ==
There are two isoforms of the Liver X Receptor:


[[File:Liver_X_Receptor.png|thumb|right|Diagram of LXR structure and function.]]
* '''LXRα''' (NR1H3) - Predominantly expressed in the [[liver]], [[adipose tissue]], [[intestine]], and [[macrophages]].
* '''LXRβ''' (NR1H2) - Ubiquitously expressed in various tissues throughout the body.


=== Isoforms ===
== Function ==
LXRs play a crucial role in maintaining [[cholesterol homeostasis]] by regulating the expression of genes involved in cholesterol efflux, transport, and excretion. They also influence [[lipogenesis]] and [[gluconeogenesis]].


* '''LXR_ (NR1H3)''': Predominantly expressed in the [[liver]], [[adipose tissue]], [[intestine]], and [[macrophages]]. It plays a significant role in the regulation of cholesterol metabolism and is involved in the reverse cholesterol transport pathway.
=== Cholesterol Metabolism ===
* '''LXR_ (NR1H2)''': Ubiquitously expressed in most tissues and is thought to have a more general role in maintaining cholesterol homeostasis.
LXRs promote the expression of genes such as [[ABCA1]] and [[ABCG1]], which are involved in the efflux of cholesterol from cells to [[high-density lipoprotein]] (HDL) particles. This process is essential for the reverse transport of cholesterol from peripheral tissues to the liver for excretion.


=== Biological Roles ===
=== Lipid Metabolism ===
In addition to cholesterol metabolism, LXRs regulate genes involved in the synthesis and storage of [[fatty acids]]. They activate [[SREBP-1c]], a key transcription factor that promotes the expression of enzymes required for fatty acid synthesis.


==== Cholesterol Metabolism ====
=== Glucose Metabolism ===
LXRs also have a role in glucose metabolism by modulating the expression of genes involved in [[gluconeogenesis]] and [[insulin sensitivity]].


LXRs are critical regulators of cholesterol homeostasis. They promote the expression of genes involved in cholesterol efflux, such as [[ABCA1]] and [[ABCG1]], which facilitate the transport of cholesterol out of cells to [[high-density lipoprotein]] (HDL) particles. This process is essential for the reverse cholesterol transport pathway, which helps to remove excess cholesterol from peripheral tissues and transport it to the liver for excretion.
== Mechanism of Action ==
LXRs function as [[heterodimers]] with the [[retinoid X receptor]] (RXR). Upon binding to their ligands, LXRs undergo a conformational change that allows them to bind to specific [[DNA sequences]] known as [[LXR response elements]] (LXREs) in the promoter regions of target genes.


==== Lipid Metabolism ====
[[File:LXR-RXR_bound_polar_contacts.png|thumb|left|300px|Polar contacts in the LXR-RXR complex.]]


In addition to cholesterol regulation, LXRs influence [[lipogenesis]] by inducing the expression of [[SREBP-1c]], a key transcription factor that promotes the synthesis of fatty acids and triglycerides. This function is particularly important in the liver and adipose tissue, where lipid storage and metabolism are tightly regulated.
== Clinical Significance ==
 
Due to their role in lipid and glucose metabolism, LXRs are considered potential therapeutic targets for the treatment of [[atherosclerosis]], [[diabetes]], and [[metabolic syndrome]]. Agonists of LXRs have been shown to reduce [[atherosclerotic plaque]] formation in animal models.
==== Glucose Homeostasis ====
 
LXRs also play a role in glucose metabolism. They have been shown to modulate the expression of genes involved in [[gluconeogenesis]] and [[glycolysis]], thereby influencing blood glucose levels and insulin sensitivity.
 
=== Clinical Implications ===
 
Given their central role in lipid and glucose metabolism, LXRs are considered potential therapeutic targets for the treatment of [[atherosclerosis]], [[diabetes]], and other metabolic disorders. Agonists of LXRs have been investigated for their ability to reduce atherosclerotic plaque formation and improve lipid profiles. However, the development of LXR-targeted therapies is complicated by the potential for side effects, such as hepatic steatosis, due to increased lipogenesis.


== Related Pages ==
== Related Pages ==
* [[Nuclear receptor]]
* [[Nuclear receptor]]
* [[Cholesterol metabolism]]
* [[Cholesterol metabolism]]
* [[Atherosclerosis]]
* [[Transcription factor]]
* [[Diabetes]]
* [[Retinoid X receptor]]
* [[Retinoid X receptor]]


[[Category:Biochemistry]]
[[Category:Transcription factors]]
[[Category:Endocrinology]]
[[Category:Nuclear receptors]]
[[Category:Metabolism]]
[[Category:Metabolism]]

Latest revision as of 14:23, 21 February 2025

Liver X Receptor[edit]

Structure of the LXRα-RXR complex.

The Liver X Receptor (LXR) is a type of nuclear receptor that functions as a transcription factor regulating the expression of genes involved in cholesterol, fatty acid, and glucose metabolism. LXRs are activated by oxysterols, which are oxidized derivatives of cholesterol.

Types[edit]

There are two isoforms of the Liver X Receptor:

Function[edit]

LXRs play a crucial role in maintaining cholesterol homeostasis by regulating the expression of genes involved in cholesterol efflux, transport, and excretion. They also influence lipogenesis and gluconeogenesis.

Cholesterol Metabolism[edit]

LXRs promote the expression of genes such as ABCA1 and ABCG1, which are involved in the efflux of cholesterol from cells to high-density lipoprotein (HDL) particles. This process is essential for the reverse transport of cholesterol from peripheral tissues to the liver for excretion.

Lipid Metabolism[edit]

In addition to cholesterol metabolism, LXRs regulate genes involved in the synthesis and storage of fatty acids. They activate SREBP-1c, a key transcription factor that promotes the expression of enzymes required for fatty acid synthesis.

Glucose Metabolism[edit]

LXRs also have a role in glucose metabolism by modulating the expression of genes involved in gluconeogenesis and insulin sensitivity.

Mechanism of Action[edit]

LXRs function as heterodimers with the retinoid X receptor (RXR). Upon binding to their ligands, LXRs undergo a conformational change that allows them to bind to specific DNA sequences known as LXR response elements (LXREs) in the promoter regions of target genes.

Polar contacts in the LXR-RXR complex.

Clinical Significance[edit]

Due to their role in lipid and glucose metabolism, LXRs are considered potential therapeutic targets for the treatment of atherosclerosis, diabetes, and metabolic syndrome. Agonists of LXRs have been shown to reduce atherosclerotic plaque formation in animal models.

Related Pages[edit]