Abstract
Although adipogenesis is associated with induction of endoplasmic reticulum (ER) stress, the role of selenoprotein S (SEPS1), an ER resident selenoprotein known to regulate ER stress and ER-associated protein degradation, is unknown. We found an inverse relationship between SEPS1 level in adipose tissue and adiposity in mice. While SEPS1 expression was increased during adipogenesis, a markedly reduced SEPS1 protein level was found in the early phase of adipogenesis due to dexamethasone (DEX)-induced proteosomal degradation of SEPS1. Overexpression of SEPS1 in the early phase of cell differentiation resulted in impairment of adipogenesis with reduced levels of CCAAT/enhancer binding protein α and other adipocyte marker genes during the course of adipogenesis. Conversely, knockdown of SEPS1 resulted in the promotion of adipogenesis. Additionally, altered SEPS1 expression was associated with changes in expression of ER stress marker genes in the early phase of adipogenesis, and ubiquitin-proteasome system (UPS)-related ubiquitination and proteasome function. Our study reveals that SEPS1 is a novel anti-adipogenic selenoprotein that modulates ER stress- and UPS-dependent adipogenesis. Our results also identifies a novel function of DEX in the regulation of adipogenesis through induction of SEPS1 degradation. Taken together, DEX-dependent degradation of SEPS1 in the early phase of adipogenesis is necessary for initiating ER stress- and UPS-dependent maturation of adipocytes.
Highlights
Adipogenesis is associated with induction of endoplasmic reticulum (ER) stress, the role of selenoprotein S (SEPS1), an ER resident selenoprotein known to regulate ER stress and ER-associated protein degradation, is unknown
The epididymal fat pad in obese mice exhibited an approximately 90% lower protein level of SEPS1 than that in lean mice as judged by immunoblot analysis (Fig. 1B). These data indicate that obesity status is inversely correlated with SEPS1 expression in adipose tissue
To further examine the role of SEPS1 in adipogenesis, the expression of SEPS1 was monitored at different stages of adipogenesis in 3T3-L1 preadipocytes
Summary
Adipogenesis is associated with induction of endoplasmic reticulum (ER) stress, the role of selenoprotein S (SEPS1), an ER resident selenoprotein known to regulate ER stress and ER-associated protein degradation, is unknown. Overexpression of SEPS1 in the early phase of cell differentiation resulted in impairment of adipogenesis with reduced levels of CCAAT/enhancer binding protein ␣ and other adipocyte marker genes during the course of adipogenesis. Altered SEPS1 expression was associated with changes in expression of ER stress marker genes in the early phase of adipogenesis, and ubiquitin-proteasome system (UPS)related ubiquitination and proteasome function. Our study reveals that SEPS1 is a novel anti-adipogenic selenoprotein that modulates ER stress- and UPS-dependent adipogenesis. Our results identifies a novel function of DEX in the regulation of adipogenesis through induction of SEPS1 degradation. DEX-dependent degradation of SEPS1 in the early phase of adipogenesis is necessary for initiating ER stress- and UPS-dependent maturation of adipocytes.—Kim, C.
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