Sesamin and Sesamolin Potentially Inhibit Adipogenesis Through Downregulating the Peroxisome Proliferator-Activated Receptor γ Protein Expression and Activity in 3T3-L1 Cells

Sesamin and sesamolin are major sesame lignans that have demonstrated anti-inflammatory, anti-cancer, and neuroprotective properties and potential benefits in liver, cardiovascular diseases, and metabolic syndrome. However, despite previous research on their anti-obesity effects and underlying mechanisms, a comprehensive investigation of these aspects is still lacking. In this study, we evaluated the regulatory effects of 20-80 μM sesamin and sesamolin on adipogenesis in vitro using 3T3-L1 cells as a model cell line. We hypothesized that the lignans would inhibit adipogenic differentiation in 3T3-L1 cells through the regulation of peroxisome proliferator-activated receptor γ (PPARγ). Our data indicate that sesamin and sesamolin inhibited the adipogenic differentiation of 3T3-L1 cells by dose-dependently decreasing lipid accumulation and triglyceride formation. Sesamin and sesamolin reduced the mRNA and protein expression of the adipogenesis-related transcription factors, PPARγ and CCAAT/enhancer-binding protein α (C/EBPα), leading to the dose-dependent downregulations of their downstream targets, FABP4, HSL, LPL, and GLUT4. In addition, glucose uptake was dose-dependently attenuated by sesamin and sesamolin in both differentiated 3T3-L1 cells and HepG2 cells. Interestingly, our results suggested that sesamin and sesamolin might directly bind to PPARγ to inhibit its transcriptional activity. Finally, sesamin and sesamolin decreased the phosphorylation of three mitogen-activated protein kinase (MAPK) signaling components in differentiated 3T3-L1 cells. Taken together, our findings suggest that sesamin and sesamolin may exhibit anti-obesity effects by potentially downregulating PPARγ and its downstream genes through the MAPK signaling pathway, offering important insights into the molecular mechanisms underlying the potential anti-obesity effects of sesamin and sesamolin.