Evaluation of intracerebroventricular treatment effect with selective agonists of GPR120 and GPR40 receptors and in high fat diet induced-obesity mice

• Grant number: 14/26942-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): June 01, 2015
• Effective date (End): February 28, 2019
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Licio Augusto Velloso
• Grantee: Nathalia Romanelli Vicente Dragano
• 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): 17/14963-6 - Effects of conditional deletion of free fatty acid receptor 1 (FFAR1) in POMC neurons on energy homeostasis, BE.EP.PD

Abstract

Over the past two decades, studies have shown that a low-grade systemic inflammatory state is associated with obesity and consumption of high fat diets, in both rodents and humans. Initially this inflammation has been described in peripheral tissues, however, a research published by our group provided the first evidence that inflammatory changes are also detectable in the hypothalamus of obese mice. In contrast, fatty acid mono- and polyunsaturated intake has been associated with numerous health benefits, including the improvement of inflammatory and autoimmune diseases. Among these benefits, it has been reported that unsaturated fatty acids play anti-inflammatory action in the hypothalamus and are capable of reversing other deleterious effects induced by diet rich in saturated fat. Recent studies revealed, at least, that some of the known anti-inflammatory effects of omega 3 fatty acids are mediated by their interaction with the receptor G protein coupled 120 (GPR 120) in macrophages and mature adipocytes. Results obtained during my PhD (unpublished and therefore confidential) revealed that the GPR120 and GPR40 are expressed in hypothalamus of mice, however, the GPR120 is expressed mainly in microglial cells and GPR40 is expressed in hypothalamic neurons. We also observed that the intracerebroventricular treatment with the synthetic agonist of GPR120, GW9508, was efficient in induced GPR120 signal transductionin the hypothalamus and that treatment with GW9508 for 6 days activates an antiinflammatory response in the hypothalamus of lean and obese mice. The objective of this study is to evaluate the effect of intracerebroventricular treatment withTUG1197 and TUG905 selective agonists for GPR120 receptor GPR40 and, respectively, on the metabolism of obese 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)

HADDAD-TOVOLLI, ROBERTA; DRAGANO, NATHALIA R. V.; RAMALHO, ALBINA F. S.; VELLOSO, LICIO A.. Development and Function of the Blood-Brain Barrier in the Context of Metabolic Control. FRONTIERS IN NEUROSCIENCE, v. 11, APR 21 2017. (15/50278-0, 15/02913-9, 14/26942-5, 16/01868-2, 13/07607-8)