Related Experiment Video

Updated: Jun 27, 2026

LDL Cholesterol Uptake Assay Using Live Cell Imaging Analysis with Cell Health Monitoring
08:45

LDL Cholesterol Uptake Assay Using Live Cell Imaging Analysis with Cell Health Monitoring

Published on: November 17, 2018

Liver X receptors (LXR) as therapeutic targets in dyslipidemia

Jerzy Bełtowski1

  • 1Department of Pathophysiology, Medical University, Lublin, Poland. jerzy.beltowski@am.lublin.pl

Cardiovascular Therapeutics
|November 28, 2008
PubMed

Insights

Liver X receptors (LXR) act as cholesterol sensors, regulating cholesterol metabolism. However, LXR agonists can promote fatty acid synthesis, leading to elevated triglycerides and liver fat, a key limitation for their therapeutic use.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pharmacology

Background:

  • Liver X receptors (LXR) alpha and beta are nuclear receptors that heterodimerize with retinoid X receptor (RXR).
  • Oxysterols, derived from cholesterol, are natural LXR ligands, while synthetic agonists like T0901317 and GW3965 have been developed.
  • LXRs function as cellular cholesterol sensors, modulating cholesterol homeostasis through various pathways.

Purpose of the Study:

  • To elucidate the role of LXRs in cholesterol metabolism and their response to natural and synthetic ligands.
  • To investigate the dual effects of LXR activation, including cholesterol regulation and lipogenesis.
  • To assess the therapeutic potential and limitations of LXR agonists as hypolipidemic agents.

Main Methods:

  • Review of existing literature on LXR structure, function, and ligand interactions.
  • Analysis of LXR-mediated gene expression pathways, including cholesterol transport and fatty acid synthesis.
  • Evaluation of the impact of LXR agonists on plasma triglycerides and liver steatosis.

Main Results:

  • LXRs regulate cholesterol absorption, efflux to HDL, and biliary excretion, acting as a protective mechanism against cholesterol overload.
  • LXR agonists stimulate sterol regulatory element-binding protein-1c (SREBP-1c), a lipogenic transcription factor.
  • Activation of lipogenesis by LXR agonists leads to elevated plasma triglycerides and hepatic steatosis, posing a significant drawback for drug development.

Conclusions:

  • LXRs play a critical role in maintaining cholesterol balance within the body.
  • The lipogenic effects of LXR agonists represent a major challenge for their application as hypolipidemic drugs.
  • Understanding LXR signaling is crucial, as it is influenced by commonly used medications like statins, fibrates, and thiazolidinediones.

More Related Videos

A Familial Hypercholesterolemia Human Liver Chimeric Mouse Model Using Induced Pluripotent Stem Cell-derived Hepatocytes10:56

A Familial Hypercholesterolemia Human Liver Chimeric Mouse Model Using Induced Pluripotent Stem Cell-derived Hepatocytes

Published on: September 15, 2018

Related Concept Videos

Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
Lipid-Lowering Drugs: Statins and Miscellaneous Agents01:20

Lipid-Lowering Drugs: Statins and Miscellaneous Agents

Hyperlipidemia, a medical condition often referred to as high cholesterol, is characterized by abnormally elevated levels of lipids in the bloodstream. When present in excess, these lipids, specifically cholesterol and triglycerides, can lead to serious health complications, often involving cardiovascular diseases. Illnesses like atherosclerosis, heart attacks, and pancreatitis have all been linked to untreated hyperlipidemia. This means controlling and regulating cholesterol and triglyceride...
Cholesterol: Significance and Regulation01:29

Cholesterol: Significance and Regulation

Although not a source of energy, cholesterol plays a significant role as a foundational structure for bile salts, steroid hormones, and vitamin D, as well as being a crucial component of plasma membranes. Approximately 15% of blood cholesterol is derived from our diet, with the remainder synthesized from acetyl CoA by the liver and intestines. Cholesterol is eliminated from the body through its conversion into bile salts, which are eventually discarded in the feces.
Considering cholesterol and...
Pharmacogenomics: Identification of New Drug Targets01:29

Pharmacogenomics: Identification of New Drug Targets

Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
Atherosclerosis III: Management01:26

Atherosclerosis III: Management

Management of atherosclerosis involves an integrated strategy encompassing pharmacological treatment, surgical interventions, lifestyle changes, and nutrition therapy to address the multifactorial nature of the disease.Pharmacological TherapyA cornerstone of atherosclerosis management is the use of pharmacological agents. Statins, such as atorvastatin, are pivotal in inhibiting HMG-CoA reductase, an enzyme that catalyzes an initial step in cholesterol synthesis in the liver. This reduction in...
Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow01:26

Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow

Chronic liver disease significantly impacts drug metabolism due to alterations in hepatic blood flow and enzyme accessibility. This disruption affects the body's pharmacokinetics—the movement and processing of drugs within the system. Key enzymes crucial for metabolizing medications become less accessible, changing how drugs are processed and utilized. Furthermore, liver disease influences the synthesis of plasma proteins, such as albumin and globulins, which play critical roles in drug binding...