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

Objectives: The aim of this study was to assess the effect of the micronutrient selenium, as inorganic selenite, on adipocytes differentiation, and to identify underlying molecular mechanisms to advance the understanding of basic cellular mechanisms associated with adipogenesis. Methods: The effect of sodium selenite (Na2SeO3) on cell viability (bromide 3-[4,5-dimethylthiazol-2-yl]-2,5difeniltetrazol [MTT] assay) in preadipocytes, lipid accumulation (oil red O [ORO] assay) and intracellular reactive oxygen species (ROS, [NBT assay]) in mature adipocytes, as well as explore molecular mechanisms via gene expression analyses (real-time quantitative polymerase chain reaction), before and after differentiation, was investigated using 3T3-L1 murine preadipocytes. Results: Selenite (100, 200, and 400 nM) significantly decreased lipid accumulation during differentiation compared with untreated adipocytes (P < 0.05, 0.001, and 0.01, respectively). Preadipocytes exposure (48 h) to selenite caused an increase in glutathione peroxidase 1 (Gpx1) gene expression in a dose-dependent manner. Adipogenesis significantly increased intracellular reactive oxygen species levels (P < 0.05) while decreasing gene expression of antioxidant enzymes (Gpx1: P < 0.05) and significantly increasing gene expression of regulators of lipid catabolism (type II iodothyronine deiodinase [Dio2], P < 0.01) and markers of differentiation (eg, seleniumbinding protein 1 [Selenbp1], peroxisome proliferator activated receptor gamma [Pparg], CCAAT/enhancer binding protein alpha [Cebpa], and fatty acid binding protein 4 [Fab4]) compared with preadipocytes (P < 0.01, 0.01, 0.01, and 0.001, respectively). Selenite exposure (200 nM) caused a significant increase in Gpx1, selenoproteinW(Selenow) and selenoprotein P (Selenop) gene expression, in adipocytes compared with untreated ones (P < 0.01, 0.001, and 0.05, respectively) with a significant decrease in heme oxygenase 1 (Ho-1), cyclooxygenase 2 (Cox2), Dio2, and Fabp4 gene expression (P < 0.001, 0.05, 0.05, and 0.01, respectively). Conclusions: Selenium, as selenite, prevented adipogenesis through increasing antioxidant selenoprotein expression, leading to decreased inflammatory markers and, subsequently, to a decrease in differentiation and lipid deposition. These findings, if demonstrated in vivo, could provide valuable data for novel dietary approaches to prevent obesity. (C) 2021 The Author(s). Published by Elsevier Inc.