Related Experiment Videos
Bezafibrate is a dual ligand for PPARalpha and PPARbeta: studies using null mice
Jeffrey M Peters1, Toshifumi Aoyama, Amanda M Burns
1Department of Veterinary Science, Center for Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, 226 Fenske Laboratory, University Park, PA 16802, USA. jmp21@psu.edu
Biochimica Et Biophysica Acta
|June 5, 2003
Summary
Bezafibrate
Area of Science:
- Pharmacology
- Molecular Biology
- Genetics
Background:
- Bezafibrate activates peroxisome proliferator-activated receptors (PPARs), specifically PPARalpha and PPARbeta.
- Understanding the specific roles of PPARalpha and PPARbeta in mediating bezafibrate's effects is crucial.
Purpose of the Study:
- To investigate the roles of PPARalpha and PPARbeta in mediating the biological effects of bezafibrate.
- To determine how bezafibrate affects gene expression and physiological parameters in the absence of functional PPARalpha or PPARbeta.
Main Methods:
- Utilized wild-type, PPARalpha-null, and PPARbeta-null mice fed either a control or bezafibrate-containing diet for 10 days.
- Analyzed liver weight, gonadal adipose stores, and mRNA expression in liver, white adipose tissue, and intestine.
- Performed Western blot analysis on liver protein to correlate with mRNA expression changes.
Main Results:
- Bezafibrate increased liver weight and reduced adipose stores in wild-type and PPARbeta-null mice, but not in PPARalpha-null mice.
- Bezafibrate altered mRNA expression of lipid metabolizing enzymes similarly in wild-type and PPARbeta-null mice.
- Interestingly, bezafibrate induced some PPARalpha-controlled genes even in PPARalpha-null mice, indicating non-exclusive modulation.
Conclusions:
- Bezafibrate's effects are largely mediated by PPARalpha, with some gene expression changes also dependent on PPARbeta.
- Unlike other PPARalpha ligands, bezafibrate can modulate certain target genes independently of a functional PPARalpha receptor.