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The role of T3 hormone on LCN2 expression and their contribution on appetite

Grant number: 19/04495-0
Support type:Scholarships in Brazil - Master
Effective date (Start): June 01, 2019
Effective date (End): May 31, 2021
Field of knowledge:Biological Sciences - Biochemistry - Chemistry of Macromolecules
Principal Investigator:Willian Fernando Zambuzzi
Grantee:Amanda Fantini de Camargo Andrade
Home Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
Associated research grant:14/22689-3 - Microvesicle/proteins-mediated paracrine signaling among bone and endothelial cells during bone development and regeneration, AP.JP

Abstract

Over the last few years we have been working on the understanding of autocrine, paracrine and endocrine mechanisms necessary for the differentiation of osteoblasts for a better understanding of the biological mechanisms governing osteogenesis and also regenerative processes. In parallel, this candidate Amanda Fantini de Camargo Andrade has received fellow from FAPESP to evaluate the osteogenic profile of mesenchymal stem cells in response to the hormone T3, during full 02 years within her undergraduate period, and altogether those results were published at Molecular and Celullar Endocrinology. In parallel, an article from the group of Professor Stravoula Kounsteni, Columbia University, USA, has shown the role of lipocalin (LCN2) on food intake. Based on these statements, our hypothesis here is that hormone T3 interferes with osteoblast activity, promoting control of LCN2 expression, and thus contributes to hypothalamic modulation of appetite. For this, our objective is firstly to evaluate the role of 3,3 ', 5 - Triiodothyronine (T3) thyroid hormone in the control of the expression of Lipocalin 2 (LCN2) in osteoblasts and adipocytes, as well as its synergism in food intake mechanism. Methodologically, we have 2 different moments: a set of in vitro tests, where we will use murine cell lines, MC3T3-E1 (osteoblasts) and 3T3-L1 (adipocytes), evaluating expression and potential epigenetic marks involved; and another set in vivo, to validate its effects at a systemic manner. The need to evaluate, in the different experimental groups, the dietary intake and modulation of MC4R receptor expression in the hypothalamus. We hope to enhance our understanding of physiological mechanism involved with food intake and appetite. In vivo methodologies will be developed with close partnership of Professor Renato Ferretti, Department of Anatomy of this Institute in Botucatu -SP, who is the co-advisor of this project. (AU)