Anti-Adipogenic Effects of Probiotic Lactiplantibacillus pentosus THF59 via Inhibition of Differentiation and Promotion of Apoptosis in 3T3-L1 Cells.

This study investigated the probiotic properties and anti-adipogenic activities of Lactiplantibacillus pentosus THF59, isolated from blueberries. THF59 exhibited several probiotic traits, including antimicrobial activity, tolerance to simulated gastric juice and bile salts, non-pathogenicity, and strong adhesion to intestinal epithelial Caco-2 cells. To evaluate its anti-adipogenic potential, MDI-induced 3T3-L1 preadipocytes were treated with THF59 cell-free supernatant (CFS). At the highest tested concentration (100 μg/mL), THF59 CFS significantly reduced intracellular lipid accumulation by 68.40%, as evidenced by Oil Red O staining. It also decreased intracellular reactive oxygen species (ROS) levels by 27.45%, potentially suppressing adipogenic differentiation by disrupting ROS-mediated early signaling events. Moreover, THF59 alleviated MDI-induced S-phase cell cycle arrest, suggesting interference with early-stage preadipocyte differentiation. At this concentration, THF59 CFS significantly downregulated key adipogenic transcription factors involved in various stages of differentiation, including SREBP-1 (68.91%), PPARγ (50.75%), C/EBPα (41.99%), and AP-2 (37.44%). These findings indicate that THF59 suppressed adipogenesis through multi-level regulatory interference, from early commitment to terminal differentiation. Notably, THF59 also promoted late-stage apoptosis in mature adipocytes by 6.55%, representing an additional lipid-lowering mechanism through the removal of lipid-storing cells. In conclusion, THF59 exerted anti-adipogenic effects in MDI-induced 3T3-L1 preadipocytes by inhibiting differentiation and promoting apoptosis, supporting its potential as a functional probiotic candidate for obesity prevention.