Selenium, as selenite, prevents adipogenesis by modulating selenoproteins gene expression and oxidative stress-related genes.

Objective: This study aimed to assess the effect of the micronutrient selenium, as inorganic selenite, on adipocytes differentiation and to identify underlying molecular mechanisms, while advancing understanding of basic cellular mechanisms associated with adipogenesis. Methods: 3T3-L1 murine preadipocytes were used to investigate the effect of sodium selenite (Na2SeO3) on cell viability (MTT assay) in preadipocytes, lipid accumulation (Oil Red O staining) and intracellular reactive oxygen species (ROS, NBT assay) in mature adipocytes, in addition to explore molecular mechanisms via gene expression analyses (RT-qPCR), pre and post differentiation. Results: Selenite (100, 200, 400nM) significantly decreased lipid accumulation during differentiation compared to untreated adipocytes (P[less than]0.05, 0.001, 0.01, respectively). Pre-adipocytes exposure (48h) to selenite caused an increase in glutathione peroxidase 1 (Gpx1) gene expression in a dose-dependent manner. Adipogenesis significantly increased intracellular ROS levels (P[less than]0.05) while decreasing gene expression of antioxidant enzymes (Gpx1, P[less than]0.05) and significantly increasing gene expression of regulators of lipid catabolism (type II iodothyronine deiodinase, Dio2, P[less than]0.01) and of markers of differentiation (e.g. selenium-binding protein 1, Selenbp1, peroxisome proliferator activated receptor gamma, Pparg, CCAAT/enhancer binding protein alpha, Cebpa, and fatty acid binding protein 4, Fabp4) compared to pre-adipocytes (P[less than]0.01, 0.01, 0.01 and 0.001, respectively). Selenite exposure (200nM) caused a significant increase in Gpx1, selenoprotein W (Selenow), selenoprotein P (Selenop) gene expression in differentiated adipocytes compared to untreated ones (P[less than]0.01, 0.001, 0.05, respectively) with a significant decrease in heme oxygenase 1 (Ho-1), cyclooxygenase 2 (Cox2), Dio2 and Fabp4 gene expression (P[less than]0.001, 0.05, 0.05 and 0.01, respectively). Conclusions: Selenium, as selenite, prevented adipogenesis through increasing antioxidant selenoproteins expression, leading to decreased inflammatory markers and, subsequently, to decrease in differentiation and lipid deposition. These findings, if demonstrated in vivo, could provide valuable data for novel dietary approaches to prevent obesity.