Related Experiment Video

Updated: Jun 17, 2026

Network Pharmacology Prediction and Metabolomics Validation of the Mechanism of Fructus Phyllanthi against Hyperlipidemia
11:06

Network Pharmacology Prediction and Metabolomics Validation of the Mechanism of Fructus Phyllanthi against Hyperlipidemia

Published on: April 7, 2023

Identification of novel pathways that control farnesoid X receptor-mediated hypocholesterolemia

Yanqiao Zhang1, Liya Yin, Jody Anderson

  • 1Department of Integrative Medical Sciences, Northeastern Ohio Universities College of Medicine, Rootstown, Ohio 44272, USA. yzhang@neoucom.edu

The Journal of Biological Chemistry
|December 10, 2009
PubMed

Insights

Farnesoid X receptor (FXR) activation lowers cholesterol by increasing scavenger receptor B type I (SR-BI) and enhancing reverse cholesterol transport. This suggests FXR as a therapeutic target for hypercholesterolemia.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Background:

  • Farnesoid X receptor (FXR) regulates bile acid, lipoprotein, and glucose metabolism.
  • Dysregulation of these pathways contributes to hypercholesterolemia and cardiovascular disease.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which FXR activation leads to reduced cholesterol levels.
  • To identify novel pathways involved in FXR-mediated cholesterol homeostasis.

Main Methods:

  • Utilized knockout mice (Fxr-/- and SR-BI deficient).
  • Employed FXR-specific agonists and adenoviral gene expression systems.
  • Investigated hepatic p-JNK, hepatocyte nuclear factor 4alpha, and SR-BI expression.

Main Results:

  • Identified a novel pathway: FXR activation impacts hepatic p-JNK, HNF4α, and SR-BI.
  • Demonstrated FXR-dependent SR-BI upregulation, leading to hypocholesterolemia and increased reverse cholesterol transport.
  • Showcased SR-BI-independent increases in reverse cholesterol transport and reduced intestinal cholesterol absorption.

Conclusions:

  • FXR activation effectively lowers cholesterol and enhances reverse cholesterol transport.
  • FXR represents a promising therapeutic target for managing hypercholesterolemia and coronary heart disease.

More Related Videos

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists10:51

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists

Published on: November 15, 2013

Related Concept Videos

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...
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:
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...
Overview of Fatty Acid Metabolism01:28

Overview of Fatty Acid Metabolism

Lipids also are sources of energy that power cellular processes. Like carbohydrates, lipids are composed of carbon, hydrogen, and oxygen, but these atoms are arranged differently. Most lipids are nonpolar and hydrophobic. Major types include fats and oils, waxes, phospholipids, and steroids.
Fatty acids are catabolized in a process called beta-oxidation, which takes place in the matrix of the mitochondria and converts their fatty acid chains into two-carbon units of acetyl groups. The acetyl...
Lipid Catabolism01:25

Lipid Catabolism

Triglycerides serve as crucial long-term energy storage molecules in microorganisms, providing a dense source of metabolic energy. Their breakdown is mediated by lipases, which hydrolyze triglycerides into glycerol and free fatty acids. Each of these components follows distinct metabolic pathways, ultimately contributing to ATP synthesis and cellular energy homeostasis.Glycerol MetabolismGlycerol, released from triglyceride hydrolysis, is phosphorylated by glycerol kinase to form...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...