PMID- 31846435 OWN - NLM STAT- MEDLINE DCOM- 20200831 LR - 20211204 IS - 1479-6805 (Electronic) IS - 0022-0795 (Linking) VI - 244 IP - 3 DP - 2020 Mar TI - Selenoprotein S regulates adipogenesis through IRE1alpha-XBP1 pathway. PG - 431-443 LID - JOE-19-0292 [pii] LID - 10.1530/JOE-19-0292 [doi] AB - The induction of endoplasmic reticulum (ER) stress is associated with adipogenesis, during which the inositol-requiring enzyme 1 alpha (IRE1alpha)-X-box-binding protein 1 (XBP1) pathway is involved. Selenoprotein S (SelS), which is an ER resident selenoprotein, is involved in ER homeostasis regulation; however, little is known about the role of SelS in regulating adipogenesis. In vivo studies showed that SelS protein levels in white adipose tissue were increased in obese subjects and high-fat diet (HFD)-fed mice. Moreover, we identified that SelS protein levels increased in the early phase of adipogenesis and then decreased in the late phase during adipogenesis. Overexpression of SelS promoted adipogenesis. Conversely, knockdown (KD) of SelS resulted in the inhibition of adipogenesis, which was related to increasing cell death, decreased mitotic clonal expansion, and cell cycle G1 arrest. In vivo studies also showed that ER stress markers (p-IRE1alpha/IRE1alpha, XBP1s, and Grp78) were significantly increased with upregulating of SelS expression in subcutaneous and visceral adipose tissues in the obese subjects and HFD-fed mice. Furthermore, in SelS KD cells, the levels of Grp78 were increased and the levels of p-IRE1alpha/IRE1alpha were unchanged , but mRNA levels of spliced XBP1 (XBP1s) produced by IRE1alpha-mediated splicing were decreased, suggesting a role of SelS in the modulation of IRE1alpha-XBP1 pathway. Moreover, inhibition of adipogenesis by SelS suppression can be rescued by overexpression of XBP1s. Thus, SelS appears to function as a novel regulator of adipogenesis through the IRE1alpha-XBP1 signaling pathway. FAU - Men, Lili AU - Men L AD - Department of Endocrinology, The First Affiliated Hospital of Dalian Medical University, Dalian, China. FAU - Yao, Junjie AU - Yao J AD - Department of Endocrinology, The First Affiliated Hospital of Dalian Medical University, Dalian, China. FAU - Yu, Shanshan AU - Yu S AD - Department of Endocrinology, The First Affiliated Hospital of Dalian Medical University, Dalian, China. FAU - Li, Yu AU - Li Y AD - Department of Endocrinology, The First Affiliated Hospital of Dalian Medical University, Dalian, China. FAU - Cui, Siyuan AU - Cui S AD - Department of Endocrinology, The First Affiliated Hospital of Dalian Medical University, Dalian, China. FAU - Jin, Shi AU - Jin S AD - Department of Laparoscopic Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China. FAU - Zhang, Guixin AU - Zhang G AD - Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China. FAU - Ren, Decheng AU - Ren D AD - Department of Medicine, The University of Chicago, Chicago, Illinois, USA. FAU - Du, Jianling AU - Du J AD - Department of Endocrinology, The First Affiliated Hospital of Dalian Medical University, Dalian, China. LA - eng GR - P30 DK020595/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - England TA - J Endocrinol JT - The Journal of endocrinology JID - 0375363 RN - 0 (Endoplasmic Reticulum Chaperone BiP) RN - 0 (HSPA5 protein, human) RN - 0 (Hspa5 protein, mouse) RN - 0 (Membrane Proteins) RN - 0 (SELENOS protein, human) RN - 0 (Selenoproteins) RN - 0 (Selenos protein, mouse) RN - 0 (X-Box Binding Protein 1) RN - 0 (XBP1 protein, human) RN - 0 (Xbp1 protein, mouse) RN - EC 2.7.11.1 (ERN1 protein, human) RN - EC 2.7.11.1 (Ern1 protein, mouse) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 3.1.- (Endoribonucleases) SB - IM MH - Adipocytes/cytology/metabolism MH - *Adipogenesis MH - Animals MH - Endoplasmic Reticulum Chaperone BiP MH - Endoribonucleases/genetics/metabolism MH - Female MH - Humans MH - Male MH - Membrane Proteins/genetics/*metabolism MH - Mice MH - Mice, Inbred C57BL MH - Protein Serine-Threonine Kinases/genetics/metabolism MH - Selenoproteins/genetics/*metabolism MH - *Signal Transduction MH - X-Box Binding Protein 1/genetics/metabolism OTO - NOTNLM OT - IRE1alpha OT - SelS OT - XBP1 OT - adipogenesis OT - endoplasmic reticulum stress EDAT- 2019/12/18 06:00 MHDA- 2020/09/01 06:00 CRDT- 2019/12/18 06:00 PHST- 2019/12/03 00:00 [received] PHST- 2019/12/16 00:00 [accepted] PHST- 2019/12/18 06:00 [pubmed] PHST- 2020/09/01 06:00 [medline] PHST- 2019/12/18 06:00 [entrez] AID - JOE-19-0292 [pii] AID - 10.1530/JOE-19-0292 [doi] PST - ppublish SO - J Endocrinol. 2020 Mar;244(3):431-443. doi: 10.1530/JOE-19-0292.