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Fenofibrate Treatment Inhibits Very-Low-Density Lipoprotein Transport Vesicle Formation by Reducing Sar1b Protein
Kayli Winterfeldt1, Fahim Rejanur Tasin1, Vandana Sekhar1
1Division of Metabolic & Cardiovascular Sciences, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, 6900 Lake Nona Blvd., Room# 349, Orlando, FL 32827, USA.
International Journal of Molecular Sciences
|May 28, 2025
Summary
Fenofibrate reduces Very Low-Density Lipoprotein (VLDL) secretion by disrupting its intracellular transport in liver cells. This novel mechanism explains how fenofibrate improves lipid profiles and may impact atherosclerosis progression.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Dyslipidemia and atherosclerosis are linked, with Very Low-Density Lipoprotein (VLDL) playing a key role in lipid homeostasis and disease progression.
- Fenofibrate, a PPARα agonist, effectively lowers triglycerides and VLDL cholesterol but its effect on VLDL intracellular trafficking is unknown.
Purpose of the Study:
- To investigate the impact of fenofibrate on the intracellular trafficking and secretion of VLDL in hepatocytes.
- To elucidate a novel mechanism of fenofibrate's lipid-altering effects.
Main Methods:
- HepG2 cells were treated with fenofibrate (50 µM).
- VLDL secretion was measured using radiolabeled and fluorescent triglycerides and ApoB100.
- Intracellular VLDL trafficking was monitored using confocal microscopy.
- Protein expression of Sar1B was analyzed via immunoblot.
Main Results:
- Fenofibrate significantly reduced VLDL secretion, indicated by decreased release of triglycerides and ApoB100.
- Confocal microscopy revealed altered VLDL triglyceride localization, suggesting delayed ER and Golgi transport.
- Fenofibrate treatment decreased Sar1B protein expression, a key regulator of VLDL transport vesicle formation.
Conclusions:
- Fenofibrate interferes with intracellular VLDL trafficking in hepatocytes.
- This disruption of VLDL transport represents a novel mechanism for fenofibrate's lipid-modulating effects.
- Understanding this mechanism may offer new insights into managing dyslipidemia and atherosclerosis.
Keywords:
Golgiatherosclerosiscoat protein complex II (COPII)endoplasmic reticulum (ER)fenofibrateintracellular traffickingvery low-density lipoprotein (VLDL)More Related Videos
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