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Effect of adipocyte knockdown of Esr1 gene on the regulation of VEGFA and Slc2a4/GLUT4 expression.

Grant number: 15/13652-1
Support Opportunities:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): January 11, 2016
Effective date (End): December 10, 2016
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Ubiratan Fabres Machado
Grantee:Luciana Alves de Fátima
Supervisor: Deborah J. Clegg
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Research place: Cedars-Sinai Medical Center, United States  
Associated to the scholarship:13/03343-6 - VEGFA-mediated role of estradiol on angiogenesis/adipogenesis process in the adipose tissue, BP.PD


Estrogen (E2) regulates the angiogenesis in different tissues and participates on the pathophysiology of the obesity and diabetes. In fat cells, E2 increases the expression of glucose transporter GLUT4 (encoded by Slc2a4 gene) as well as glucose uptake, increasing insulin sensitivity. It is known that E2 is able to modulated vascular endothelial growth factor (VEGFA) expression, which is the main angiogenic factor on the adipose tissue. The interplay between estrogen and VEGFA regulation might interfere on the adipose tissue physiology and consequently on the obesity and insulin resistance. We hypothesized that, in adipocytes, the E2-induced expression of VEGFA and GLUT4/Slc2a4 is mainly mediated via estrogen receptor alpha (ESR1) pathway. We have already observed that E2 and the activation ESR1 increased VEGFA and GLUT4/Slc2a4 expression in 3T3-L1 cells. Thus, to contribute with these results, the aim of the present project is to investigate the role of ESR1 in the regulation of VEGFA, GLUT4 and the transcriptional factors CEBPA (CCAAT/enhancer binding protein, alpha) and HIF1A (hypoxia inducible factor 1, alpha subunit) expression. For this, in vitro transfection of 3T3-L1 adipocytes to knockdown Esr1 gene will be performed. After that, the adipocytes will be treated or not with 17²-estradiol and subsequent analysis of the genes and proteins VEGFA, GLUT4/Slc2a4, CEBPA and HIF1A will be performed using real time PCR and western blotting respectively. Thereby, we expect to better understand the involvement of ESR1 in VEGFA and GLUT4 regulation by E2.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
FATIMA, L. A.; CAMPELLO, R. S.; SANTOS, R. DE SOUZA; FREITAS, H. S.; FRANK, A. P.; MACHADO, U. F.; CLEGG, D. J.. Estrogen receptor 1 (ESR1) regulates VEGFA in adipose tissue. SCIENTIFIC REPORTS, v. 7, . (15/13652-1, 12/04831-1, 13/03343-6)

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