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W3 and W9 fatty acids as inflammatory pathway blockers through GPR120 receptor: a multi-organic approach

Grant number: 12/07129-6
Support type:Research Grants - Young Investigators Grants
Duration: November 01, 2013 - October 31, 2016
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Dennys Esper Corrêa Cintra
Grantee:Dennys Esper Corrêa Cintra
Home Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
Assoc. researchers:Augusto Ducati Luchessi ; Eduardo Rochete Ropelle ; José Rodrigo Pauli ; Licio Augusto Velloso
Associated scholarship(s):13/25742-0 - Unsaturated fatty acids in the modulation of inflammatory phenomenon and endoplasmatic reticulum stress in the arterial wall of obese and diabetic animals: role of GPR120 receptor, BP.MS
13/26149-0 - Hepatic glucose production mediated by unsaturated fatty acids: the role of GQ11 protein, BP.DR

Abstract

Obesity is currently the most important public health problems and has been considered a disease out of control. In association, a constellation of diseases such as insulin resistance, hypertension, dyslipidemia, atherosclerosis, and, among others, some types of cancers, are responsible for high rates of mortality or functional disability. These diseases show a common factor, the phenomenon characterized by a chronic and low-grade inflammatory, which act as initiator or enhancer in the genesis of these metabolic disorders. The current understanding of these phenomena emerged the "metaflamation" term, where pro-inflammatory peptides are present and responsible for molecular orchestration that finishes in metabolic chaos. Currently was identified in rodent's liver and adipose tissue a receptor 120 coupled to G protein (GPR-120) as well as the specific intracellular signaling cascade. This receptor is responsible for the recognition of unsaturated fatty acids like omega-3 (W3) and 9 (W9), and regulation of potent anti-inflammatory responses targeted by these compounds. Synthetic substances are known agonists of this receptor, which opens in turn, potential avenues for therapeutic use, since unraveled the intricate cellular mechanisms that regulate this function. Our group showed recently the existence and functionality of this receptor and its specific mechanism in the CNS. After treatment with W3 and 9 the control of food intake was restored. The insulin resistance in controller's neurons of orexigenic and thermogenesis responses in obese and diabetic animals was re-established. The purpose of this paper is to demonstrate the existence and functionality of this receptor in different peripheral tissues such as muscle, liver, adipose, aorta, lung, and retina, and the profile of the systemic immune response, which is profoundly affected by obesity and diabetes. Several studies have demonstrated the action of acids W3 and 9 in these tissues, and improving conditions linked to atherosclerosis, asthma, immunosuppression, and retinopathy, however, the mechanism that coordinates these phenomena is still misunderstood. (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)
DATILO, MARCELLA NEVES; SANT'ANA, MARCELLA RAMOS; FORMIGARI, GUILHERME PEDRON; RODRIGUES, PATRICIA BRITO; DE MOURA, LEANDRO PEREIRA; RAMOS DA SILVA, ADELINO SANCHEZ; ROPELLE, EDUARDO ROCHETE; PAULI, JOSE RODRIGO; CINTRA, DENNYS ESPER. Omega-3 from Flaxseed Oil Protects Obese Mice Against Diabetic Retinopathy Through GPR120 Receptor. SCIENTIFIC REPORTS, v. 8, SEP 25 2018. Web of Science Citations: 4.
MOURA-ASSIS, ALEXANDRE; AFONSO, MILESSA SILVA; DE OLIVEIRA, VANESSA; MORARI, JOSEANE; DOS SANTOS, GUSTAVO APARECIDO; KOIKE, MARCIA; LOTTENBERG, ANA MARIA; CATHARINO, RODRIGO RAMOS; VELLOSO, LICIO AUGUSTO; RAMOS DA SILVA, ADELINO SANCHEZ; DE MOURA, L. P.; ROPELLE, EDUARDO ROCHETE; PAULI, JOSE RODRIGO; CORREA CINTRA, DENNYS ESPER. Flaxseed oil rich in omega-3 protects aorta against inflammation and endoplasmic reticulum stress partially mediated by GPR120 receptor in obese, diabetic and dyslipidemic mice models. JOURNAL OF NUTRITIONAL BIOCHEMISTRY, v. 53, p. 9-19, MAR 2018. Web of Science Citations: 8.
OLIVEIRA, V.; MARINHO, R.; VITORINO, D.; SANTOS, G. A.; MORAES, J. C.; DRAGANO, N.; SARTORI-CINTRA, A.; PEREIRA, L.; CATHARINO, R. R.; DA SILVA, A. S. R.; ROPELLE, E. R.; PAULI, J. R.; DE SOUZA, C. T.; VELLOSO, L. A.; CINTRA, D. E. Diets Containing alpha-Linolenic (omega 3) or Oleic (omega 9) Fatty Acids Rescues Obese Mice From Insulin Resistance. Endocrinology, v. 156, n. 11, p. 4033-4046, NOV 2015. Web of Science Citations: 31.

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