Related Experiment Video

Updated: Nov 25, 2025

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

2.5K

The pharmacodynamic and differential gene expression analysis of PPAR α/δ agonist GFT505 in CDAHFD-induced NASH model

Linfu Liu1,2, Chuang Liu1,2, Manyu Zhao1

  • 1West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.

Plos One
|December 16, 2020
PubMed

Insights

Dual peroxisome proliferator-activated receptor α/δ (PPAR α/δ) agonists like elafibranor show promise for non-alcoholic steatohepatitis (NASH). This study reveals elafibranor

Area of Science:

  • * Pharmacology
  • * Molecular Biology
  • * Gastroenterology

Background:

  • * Non-alcoholic steatohepatitis (NASH) is a complex liver disease with limited treatment options.
  • * Peroxisome proliferator-activated receptor α/δ (PPAR α/δ) are key regulators of glucolipid metabolism and inflammation, representing a promising therapeutic target for NASH.
  • * Dual PPAR α/δ agonists, such as elafibranor (GFT505), have shown potential in clinical trials for NASH treatment.

Purpose of the Study:

  • * To investigate the pharmacodynamics and transcriptome regulation of the dual PPAR α/δ agonist elafibranor (GFT505) in a mouse model of NASH.
  • * To elucidate the molecular mechanisms underlying the therapeutic effects of elafibranor in NASH.
  • * To identify key genes and pathways modulated by elafibranor treatment in NASH.

Main Methods:

  • * Establishment of a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) induced NASH mouse model.
  • * Treatment of NASH mice with elafibranor (GFT505).
  • * Comprehensive analysis using RNA-sequencing to profile transcriptome changes and RT-qPCR to validate key differentially expressed genes.

Main Results:

  • * Elafibranor (GFT505) significantly ameliorated hepatic steatosis, inflammation, and fibrosis in CDAHFD-induced NASH mice.
  • * RNA-sequencing identified 3995 up-regulated and 3576 down-regulated genes following elafibranor treatment.
  • * Key genes involved in glucolipid metabolism, inflammation, and fibrosis pathways were significantly modulated, with enrichment analysis highlighting PPAR signaling and fatty acid degradation pathways (up-regulated) and cytokine-cytokine receptor and ECM-receptor interaction pathways (down-regulated).

Conclusions:

  • * Elafibranor (GFT505) demonstrates significant therapeutic efficacy in a preclinical NASH model by modulating key metabolic, inflammatory, and fibrotic pathways.
  • * The study provides a detailed transcriptomic profile of elafibranor's action, offering insights into its mechanism of action in NASH.
  • * These findings support further investigation into dual PPAR α/δ agonists as a therapeutic strategy for NASH.

More Related Videos

Investigating the Protective Effects of Platycodin D on Non-Alcoholic Fatty Liver Disease in a Palmitic Acid-Induced In Vitro Model08:20

Investigating the Protective Effects of Platycodin D on Non-Alcoholic Fatty Liver Disease in a Palmitic Acid-Induced In Vitro Model

Published on: December 2, 2022

2.1K
Inducing and Characterizing Vesicular Steatosis in Differentiated HepaRG Cells09:15

Inducing and Characterizing Vesicular Steatosis in Differentiated HepaRG Cells

Published on: July 18, 2019

9.2K

Related Concept Videos

GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
6.5K
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
15.1K