Squalene isolated from Schizochytrium mangrovei is a peroxisome proliferator-activated receptor-α agonist that regulates lipid metabolism in HepG2 cells.

Objective: Peroxisome proliferator-activated receptor-alpha (PPARα) is a nuclear receptor that has critical roles in the treatment of atherosclerosis, hyperlipidemia and hepatic steatosis.

Results: Squalene is a novel nature PPARα agonist, identified from reporter gene assay and qPCR analysis. Cultured hepatocytes stimulated with squalene exhibited significantly decreased cellular triacylglycerols and cholesterol concentrations, while cellular uptake of fatty acids was increased. Quantitative PCR analysis revealed that expression of genes related to fatty acid uptake, fatty acid oxidation, ketogenesis and reverse cholesterol transport metabolism were upregulated, while that of genes related to fatty acid synthesis were suppressed in cell treated with squalene.

Conclusion: Squalene is hypolipidemic by activation of PPARα via a ligand-mediated mechanism that regulates the expression of lipid metabolism genes in hepatocytes.