Involvement of PPARgamma in development of low-intensity chronic inflammation and insulin resistance associated with obesity. Participation in the actions of omega-3 fatty acids.

• Grant number: 11/14172-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: November 01, 2011
• End date: October 31, 2015
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: William Tadeu Lara Festuccia
• Grantee: Thiago Belchior de Oliveira
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 09/15354-7 - Role of adipose tissue in the development of obesity and associated co-morbidities: investigation of molecular mechanism and search for alternative therapies, AP.JP

Abstract

The World Health Organization (WHO) estimate that in the world, obesity affects one in ten adults. Overweight and obesity are major risk factors for the development of various pathologies such as metabolic syndrome, type 2 diabetes, dyslipidemia, cardiovascular disease and some type of cancers. There is evidence that low-intensity chronic inflammation, a phenotype often associated with obesity, may play an important role in the development of these pathologies. Despite the association between inflammation and obesity is well established, the factors that trigger and connect these two conditions have not been identified. This project aims to elucidate the general involvement of nuclear receptors PPAR gamma in the pathogenesis of obesity and inflammation, as well as their participation to metabolic and immunologic actions of omega-3 fatty acids. More specifically, wild mice and FAT-1 (genetically modified to produce omega-3) induced obese by eating high-fat diet and treated or not with PPAR gamma antagonist will be evaluated for changes in carbohydrates attained homeostasis (tolerance, uptake and metabolism glucose) and lipid (clearance, uptake and lipid metabolism),intracellular insulin signaling and cytokine gene expression profile, endocrine function (production and secretion of adipokines / cytokines and nitric oxide) of adipocytes and macrophages and the recruitment and change phenotype of resident macrophages in adipose tissue. The same parameters will be evaluated in mice or wild-specific deletion of specific PPAR gamma in myeloid cells. These experiments will be complemented by in vitro studies in primary cells (macrophages and adipocytes) and permanent or permanent cell lines.

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)

BELCHIOR, THIAGO; PASCHOAL, VIVIAN A.; MAGDALON, JULIANA; CHIMIN, PATRICIA; FARIAS, TALITA M.; CHAVES-FILHO, ADRIANO B.; GORJAO, RENATA; ST-PIERRE, PHILIPPE; MIYAMOTO, SAYURI; KANG, JING X.; et al. Omega-3 fatty acids protect from diet-induced obesity, glucose intolerance, and adipose tissue inflammation through PPAR gamma-dependent and PPAR gamma-independent actions. MOLECULAR NUTRITION & FOOD RESEARCH, v. 59, n. 5, p. 957-967, MAY 2015. (11/14172-2, 09/15354-7)

Academic Publications

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

OLIVEIRA, Thiago Belchior de. PPARγ involvement in the metabolic actions of ômega-3 fatty acids.. 2015. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.