Selenium inhibits adipogenesis through suppression of ER‐stress and induction of selenoprotein S

Adipogenesis is a potential target to treat or prevent obesity. It is associated with an induction of cellular stress such as endoplasmic reticulum (ER) stress. Selenium, a micronutrient, elicits a variety of health benefits, mainly through its incorporation into selenoproteins. Among those, an ER resident Selenoprotein S (SEPS1) has been shown to attenuate ER stress and the unfolded protein response. The objective of this study was to determine the role of selenium supplementation in modulating adipogenesis and its related ER stress in vitro . Exposure of 3T3‐L1 preadipocytes to selenate over a 6‐day differentiation program dose‐dependently inhibited adipogenesis without any cytotoxic effect. Consistent with this finding, adipogenic gene expressions, such as peroxisome proliferator‐activated receptor‐gamma and fatty acid synthase, were suppressed in the presence of selenate. The early stage of adipogenesis was found to be critical for selenate's inhibitory action on differentiation. Furthermore, a 24 h selenate pretreatment suppressed adipogenesis. We found that the selenate‐inhibited adipogenesis is associated with alteration of ER stress in 3T3‐L1 cells. Selenate treatment suppressed X‐box protein 1 mRNA expression and increased SEPS1 protein level during the early stages of differentiation. Furthermore, 3T3‐L1 preadipocytes transducted with lentivirus containing SEPS1 shRNA significantly blunted selenate‐inhibited adipogenesis, suggesting a requirement of SEPS1 in mediating anti‐adipogenic role of selenate. Taken together, our results indicate that selenate plays both inhibitory and preventive function in adipogenesis and this is possibly through modulation of SEPS1‐mediated ER stress. Grant Funding Source : Purdue Research Foundation, Agriculture Research Program of Purdue University