PMID- 31100494 OWN - NLM STAT- MEDLINE DCOM- 20200624 LR - 20200624 IS - 1872-8057 (Electronic) IS - 0303-7207 (Linking) VI - 498 DP - 2019 Dec 1 TI - Estradiol stimulates adipogenesis and Slc2a4/GLUT4 expression via ESR1-mediated activation of CEBPA. PG - 110447 LID - S0303-7207(19)30149-2 [pii] LID - 10.1016/j.mce.2019.05.006 [doi] AB - The ability of adipose tissue to expand is dependent on adipocyte differentiation and adipose tissue glucose disposal. The CCAAT/enhancer-binding protein alpha (CEBPA) enhances the expression of the Slc2a4 gene and GLUT4 protein, which are markers of adipocyte differentiation/glucose disposal. We hypothesized estradiol (E2) facilitates adipocyte differentiation/glucose disposal by an estrogen receptor 1 (ESR1)-dependent and CEBPA-mediated mechanism. Our results suggest that E2 (10 nM) has a positive effect on 3T3-L1 adipocyte differentiation (days 2-8), lipid accumulation, Slc2a4 and Cebpa mRNA expression, total GLUT4 and nuclear CEBPA contents, and CEBP/Slc2a4-binding activity. Esr1 silencing ( approximately 50%) in mature adipocytes abrogates the 24-h E2 effects on nuclear CEBPA content, Slc2a4/GLUT4 expression and GLUT4 translocation to the cell membrane. Thus, E2 stimulates adipocyte differentiation and Slc2a4/GLUT4 expression in an ESR1/CEBPA-mediated pathway. Our data provide mechanistic insight demonstrating E2 participates in adipose-tissue differentiation and glucose transporter expression which ultimately can improve adipose tissue expandability and glycemic control. CI - Copyright (c) 2019 Elsevier B.V. All rights reserved. FAU - Fatima, Luciana A AU - Fatima LA AD - Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil. FAU - Campello, Raquel S AU - Campello RS AD - Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil. FAU - Barreto-Andrade, Joao N AU - Barreto-Andrade JN AD - Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil. FAU - Passarelli, Marisa AU - Passarelli M AD - Lipids Laboratory (LIM 10), Medical School, University of Sao Paulo, Sao Paulo, Brazil; Graduate Studies Program in Medicine, University Nove Nove de Julho, Sao Paulo, Brazil. FAU - Santos, Roberta S AU - Santos RS AD - Biomedical Research Department, Diabetes and Obesity Research Division, Cedars-Sinai Medical Center, Los Angeles, CA, USA. FAU - Clegg, Deborah J AU - Clegg DJ AD - Biomedical Research Department, Diabetes and Obesity Research Division, Cedars-Sinai Medical Center, Los Angeles, CA, USA. FAU - Machado, Ubiratan F AU - Machado UF AD - Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil. Electronic address: ubiratan@icb.usp.br. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190514 PL - Ireland TA - Mol Cell Endocrinol JT - Molecular and cellular endocrinology JID - 7500844 RN - 0 (CCAAT-Enhancer-Binding Proteins) RN - 0 (CEBPA protein, mouse) RN - 0 (Esr1 protein, mouse) RN - 0 (Estrogen Receptor alpha) RN - 0 (Estrogens) RN - 0 (Glucose Transporter Type 4) RN - 0 (Slc2a4 protein, mouse) RN - 4TI98Z838E (Estradiol) SB - IM MH - 3T3-L1 Cells MH - Adipocytes/*cytology/drug effects/metabolism MH - Adipogenesis/*drug effects MH - Animals MH - CCAAT-Enhancer-Binding Proteins/genetics/*metabolism MH - Cell Differentiation MH - Estradiol/*pharmacology MH - Estrogen Receptor alpha/*physiology MH - Estrogens/pharmacology MH - Female MH - Gene Expression Regulation/*drug effects MH - Glucose Transporter Type 4/genetics/*metabolism MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Promoter Regions, Genetic OTO - NOTNLM OT - 3T3-L1 adipocytes OT - Adipogenesis OT - CEBPA OT - ESR1-Silencing OT - GLUT4 OT - Slc2a4 EDAT- 2019/05/18 06:00 MHDA- 2020/06/25 06:00 CRDT- 2019/05/18 06:00 PHST- 2019/03/02 00:00 [received] PHST- 2019/05/10 00:00 [revised] PHST- 2019/05/10 00:00 [accepted] PHST- 2019/05/18 06:00 [pubmed] PHST- 2020/06/25 06:00 [medline] PHST- 2019/05/18 06:00 [entrez] AID - S0303-7207(19)30149-2 [pii] AID - 10.1016/j.mce.2019.05.006 [doi] PST - ppublish SO - Mol Cell Endocrinol. 2019 Dec 1;498:110447. doi: 10.1016/j.mce.2019.05.006. Epub 2019 May 14.