title: Dexamethasone-induced selenoprotein S degradation is required for adipogenesis.
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.
authors.affiliation: Department of Food Science, Purdue University, West Lafayette, IN 47907.
authors.forename: Choon Young
authors.initials: CY
authors.lastname: Kim
authors.affiliation: Department of Food Science, Purdue University, West Lafayette, IN 47907. Electronic address: keehong@purdue.edu.
authors.forename: Kee-Hong
authors.initials: KH
authors.lastname: Kim
mesh_terms: D041721:3T3-L1 Cells; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D059748:Proteolysis / Q000187:drug effects*; D051140:Selenoproteins / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D051140:Selenoproteins; C532537:Selenos protein, mouse; D003907:Dexamethasone
keywords: 3T3-L1; adipocytes; endoplasmic reticulum stress; endoplasmic reticulum-associated protein degradation; glucocorticoid; selenoprotein S; ubiquitin-proteasome system