Use of quelantes as an alternative in the treatment of obesity: actions on the remodeling of the adipose tissue

Author(s)

Thainá Rodrigues de Morais

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas
• Defense date: 0000-00-00

Examining board members

Alessandra Gambero; Milena Monfort Pires; Uliana Sbeguen Stotzer

• Advisor: Alessandra Gambero

Abstract

The progression of obesity contributes to the increased deposition of the components of the extracellular matrix (ECM) and consequently a fibrotic condition. The accumulation of iron is also related to fibrotic process; however iron chelators therapy control then and altering the progression of numerous diseases. This study evaluated the possibility of using iron chelators as an alternative in the treatment of obesity, the ability of iron chelators to alter the production of ECM in an experimental model of adipocytes in vitro and in mice with obesity induced by a high-fat diet (HFD). Murine cell lines 3T3-L1 and Raw 264.7, as well as, 3T3-L1 differentiated into adipocytes were used. The analysis of the ECM production was performed by Sirius Red staining, using TGF-ß1 as a stimulus as well as cell proliferation was assayed with sulphorrodamine B in cells pre-treated with iron chelators, deferoxamine (DFO 0,1mM), deferiprone (DFP 0,1mM) and deferasirox (DFX 0,03mM). Swiss mice were fed a standard AIN-93 diet (CN) or HFD for 12 weeks. Treatment with DFO (100mg / kg / day; via i.p.) was performed during the last two weeks of the protocol. Body weight, adiposity, metabolic parameters were evaluated. The size of the adipocytes was evaluated as well as the presence of fibrosis was evaluated by Sirius Red. The gene expression of ECM components in the white adipose tissue (WAT) was evaluated using qRT-PCR. Treatment with DFO and deferiprone in 3T3-L1 undifferentiated cells resulted in decreased ECM, as well as decreased cell proliferation. Treatment with DFO was able to decrease the epididymal and subcutaneous depots, although it increases the size of adipocytes, restores insulin tolerance, decreases the extracellular collagen deposit and decreases the expression of COL1, COL3 and COL6 genes. Thus, we can suggest that the use of DFO may be an alternative in the treatment of obesity, with a focus on reducing ECM and improving metabolic parameters such as insulin tolerance. (AU)

• FAPESP's process: 18/03665-7 - Iron chelators activity on adipose tissue and skeletal muscle in obese mice and in vitro in 3T3-L1 and C2C12 cells
• Grantee: Thainá Rodrigues de Morais
• Support Opportunities: Scholarships in Brazil - Master