Effect of a new inhibitor of adenosine kinase (ADK) in energetic metabolism in obese mice

• Grant number: 16/05312-9
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: July 01, 2016
• End date: June 30, 2019
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Mario Jose Abdalla Saad
• Grantee: Rafael Ludemann Camargo
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 13/07607-8 - OCRC - Obesity and Comorbidities Research Center, AP.CEPID
• Associated scholarship(s): 17/10058-7 - THE ROLE OF PURINERGIC SIGNALING AND METABOLISM: "Effect of a new inhibitor of adenosine kinase (ADK) in murine and human adipocyte and in energy metabolism of obese mice", BE.EP.PD

Abstract

Obesity is characterized by an energy imbalance in favor of the accumulation of energy by white adispe tissue (WAT). The consumption of high-fat-diet (HFD) can overcome genetic obesity promoting factors. In addition to the WAT hypertrophy, obesity is associated with several comorbidities. The hypothalamus is the region of the brain responsible for the regulation of food intake by modulating the release of orexigenic and anorexigenic neuropeptides. Besides of the hypothalamus, the brown adipose tissue (BAT) also contributes to the energy balance through the activation of the thermogenic protein UCP1, which acts by uncoupling oxidative phosphorylation, dissipating energy as heat. The BAT is considered an important target in the weight loss battle. Although there are many drugs to combat obesity and metabolic diseases in general, several studies have been carried out in order to bring new therapies for the prevention and treatment of obesity. In this scenario, recent studies have demonstrated the role of adenosine as an important signaling molecule in tissues related to energy expenditure. The adenosine kinase (ADK) is one of the key enzymes in the metabolism of adenosine. The adenosine signaling has been associated with an improvement in the inflammatory process and glucose homeostasis in models of obesity. Recent studies point to adenosine as an important signaling molecule in the BAT and hypothalamus, promoting greater energy expenditure and reducing food intake. The purpose of this study is to investigate a new pharmacological inhibitor compound of the ADK enzyme in energy metabolism in obese mice. This inhibitor may be a new ally for the treatment of obesity, acting on glucose metabolism and also in the expense and comsumption of energy. (AU)