Toona sinensis leaf extract inhibits lipid accumulation through up-regulation of genes involved in lipolysis and fatty acid oxidation in adipocytes

Toona sinensis leaf (TSL) has been shown to lower plasma triacylglycerol levels and diminish the size of visceral fat cells in vivo. The molecular mechanism of TSL ethanol extract (TSL-E) on lipid metabolism in 3T3-L1 adipocytes was investigated in this study. Oil Red O staining as well as immunoblotting, real-time PCR, and dual-Luciferase reporter system were performed to investigate the effect of TSL-E on lipid accumulation and the regulation of lipid metabolism, respectively. In addition, active compounds in the TSL-E were analyzed by HPLC. TSL-E significantly decreased lipid accumulation, stimulated free fatty acid (FFA) release, and up-regulated peroxisome proliferator-activated receptor-α (PPARα) and genes involved in peroxisomal (acyl-CoA oxidase) and mitochondrial (uncouple protein 3) fatty acid oxidation. TSL-E also up-regulated cytoplasmic triacylglycerol hydrolysis gene (adipose triglyceride lipase) and genes related to fatty acid oxidation (AMP-activated protein kinase, acetyl-CoA carboxylase, carnitine palmitoyltransferase I, PPARγ, and adiponectin). The major constituents directly inducing PPARα transactivity in TSL-E are gallic acid, rutin, palmitic acid, linoleic acid, and α-linolenic acid. These results indicate that the inhibitory effect of TSL-E on lipid accumulation was through PPARα activation and further up-regulation of PPARα-mediated genes plus up-regulation of cytoplasmic genes involved in lipid catabolism.