Iron chelators activity on adipose tissue and skeletal muscle in obese mice and in vitro in 3T3-L1 and C2C12 cells

• Grant number: 18/03665-7
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): July 01, 2018
• Effective date (End): August 31, 2020
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Alessandra Gambero
• Grantee: Thainá Rodrigues de Morais
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Biometals such as iron, zinc and chromium exhibit important metabolic effects and may alter metabolic homeostasis and/or interfere with the progression of metabolic diseases as diabetes. These biometals must be consumed in the diet, absorbed, stored and distributed appropriately to the target tissues, to perform their biological function, because failures in this process result in deficiencies or overloads resulting in toxic effects. In these cases, tools are used as chelators that bind to metals. Iron chelators can be divided into three main groups: hexadentate compounds such as deferoxamine (DFO), bidentate compounds such as deferiprone (DFP) and tridentate compounds such as deferasirox (DFX). The potential effects of iron chelators have been little explored until now in a model of obesity induced by high-fat diet, where there is the occurrence of inflammation, extracellular matrix changes (fibrosis), deficient vascularization and insulin resistance in adipose tissue. Chelators could potentially increase the angiogenic response, reduce oxidative stress and pathways leading to fibrosis, exert anti-inflammatory effects, and also promote beneficial metabolic effects by restoring insulin signaling. The 3T3-L1 cell line has been used in researches related to adipose tissue pathophysiology allowing the obtainment of more controlled responses when placed in a hypoxic environment or in contact with inflammatory cells. The actions of iron chelators on skeletal muscle are much less addressed indicating antioxidant actions only. Similarly the in vitro model of C2C12 myocytes may be useful in studies of skeletal muscle alterations in obesity, serving to understand the possible actions of chelators on insulin signaling and muscle metabolism.In this way, this project aims to evaluate the actions of the iron chelants deferasirox, deferoxamine and deferiprone in vitro evaluating responses related to the production of extracellular matrix, production of inflammatory mediators, fibrotic and angiogenic factors in 3T3-L1 and metabolic and insulin signaling pathways in C2C12. In addition, we aim to evaluating the potential of iron chelators on the systemic alterations, adipose tissue and skeletal muscle in obesity induced by high-fat diet in mice. (AU)

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)

DE MORAIS, THAIND RODRIGUES; GAMBERO, ALESSANDRA. Iron chelators in obesity therapy - Old drugs from a new perspective?. European Journal of Pharmacology, v. 861, OCT 15 2019. (18/03665-7)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

MORAIS, Thainá Rodrigues de. Use of quelantes as an alternative in the treatment of obesity: actions on the remodeling of the adipose tissue. 0000. Master's Dissertation - Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas Campinas, SP.