Modulation of inflammation and insulin resistance by omega-3 fatty acids and palmitoleate

• Grant number: 10/02963-2
• Support Opportunities: Research Projects - Thematic Grants
• Start date: March 01, 2011
• End date: February 28, 2017
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Joaquim Procopio de Araujo Filho
• Grantee: Joaquim Procopio de Araujo Filho
• Host Institution: Centro de Ciências Biológicas e da Saúde. Universidade Cruzeiro do Sul (UNICSUL). São Paulo , SP, Brazil
• Pesquisadores principais: Sandro Massao Hirabara ; Tania Cristina Pithon Curi
• Associated researchers: Renata Gorjao
• Associated research grant(s): 12/07312-5 - Lipids and cell function - a journey into the world of lipids to understand its function in cell physiology, PUB.LVR.BR; 10/11295-3 - Techniques directed to the study of the hepatic metabolism: effect of diet, fatty acids, and physical activity, AV.BR
• Associated scholarship(s): 12/14201-5 - EFFECT OF N-3 FATTY ACID RICH HIGH-FAT DIET ON LYMPHOCYTE ACTIVATION MARKERS MODULATED BY ARTHRITIS INDUCTION ON C57BL/6 MICE, BP.IC; 12/02073-2 - Molecular basis of the regulation of muscle stem cell activation, proliferation and differentiation in diabetes mellitus, BP.PD; 11/02234-3 - Fatty acids and diabetes as modulators of inflammatory phase of wound healing process, BP.PD; + associated scholarships 10/18921-7 - Pathways of protein synthesis and degradation in the insulin resistance induced by hyperlipidic diet: effect of the omega-3 fatty acid supplementation and aerobic exercise training, BP.DR; 11/06815-0 - Myogenesis and regeneration of skeletal muscle: possible modulation by linoleic acid, BP.DR; 10/20322-4 - The role of peroxisomal function on the prevention of obesity and glucose intolerance, BP.PD; 10/15124-9 - Modulation of inflammatory response and insulin resistance induced by omega-3 fatty acids and exercise training in skeletal muscle from mouse fed with high fat diet: the role of TLR-4 and TNFR1, BP.PD; 10/07630-1 - Signaling pathways activated by GPR43 and their involvement in neutrophils migration in vitro and in experimental model of periodontal disease, BP.PD; 10/07596-8 - Evaluation of DNA methylation changes by high-fat-induced obesity and a possible modulated efect of omega-3 fatty acids in vivo, BP.PD - associated scholarships

Abstract

In despite of the fact that there are several studies showing the effects of fatty acids (FAs) on systemic metabolism and the consensus that high fat content in the diet is associated with insulin resistance and metabolic syndrome, the knowledge about omega-3 and omega-7 FAs related to inflammatory processes, insulin resistance, and, if there are additive or synergistic effects with regular physical exercise, is still incipient. The aim of this project is to investigate the effect of supplementation with omega-3 (fish oil) and omega-7 (macadamia oil) FAs, associated or not with regular physical activity, on inflammation and insulin resistance induced by high-fat diet. The following mice strains will be used: (1) C57BL/6, (2) Swiss, (3) knockout for TNF-alfa receptor (TNF-R1 -/-), (4) knockout for TLR-4 (TLR-4 -/-), (5) C3H/HeJ, (6) knockout for gp91phox (gp91phox -/-) and (7) transgenic mice that over express fat-1 gene (fat-1 +/+). Leukocytes (macrophages and neutrophils), skeletal muscle, adipose tissue and liver will be investigated. Mice will receive a balanced diet, supplemented or not with FAs during 12 weeks (weeks 0 to 12). In the weeks 5 to 12, a group of mice will continue receiving balanced diet and another group will receive high-fat diet. Trained mice will be submitted to treadmill exercise from week 0 to 12. At the end of the treatment, the following assessments will be perform: insulin sensitivity, inflammatory markers, glucose and FA metabolism, signaling, mitochondrial function, generation of reactive oxygen species (ROS), leukocyte function (cytokine production and phagocytosis), proteomic analysis and expression of genes related to glucose and FAs metabolism (GLUT-2, GLUT-4, FABPs, SCD-1, CPT1, CPT2, phosphoenolpyruvate carboxykinase, phosphofructokinase, citrate synthase), insulin signaling (insulin receptor, IRS-1 , IRS-2, Akt, GSK-3, MAPKs), inflammation (TNF-alfa JNK, NFºB, IL-6, IL-10, IL-1ra, ROS generation (MnSOD, CuZnSOD, catalase), and other genes also related to inflammation and obesity (PAI-1, leptin, resistin, adiponectin, MCP-1, PPARs, PGC-1alfa). A better understanding of the mechanisms involved in the action of FAs, associated or not with regular physical activity, will have direct impact on the elucidation of the issues related to obesity and associated conditions, as well as the development of new therapies that target intracellular pathways involved in inflammation. (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)

ALMEIDA, GERMANA P. L.; TROMBETTA, IVANI C.; CEPEDA, FELIPE X.; HATANAKA, ELAINE; CURI, RUI; MOSTARDA, CRISTIANO; IRIGOYEN, MARIA C.; BARRETO-FILHO, JOSE A. S.; KRIEGER, EDUARDO M.; CONSOLIM-COLOMBO, FERNANDA M.. The Role of Acute Intermittent Hypoxia in Neutrophil-Generated Superoxide, Sympathovagal Balance, and Vascular Functionin Healthy Subjects. FRONTIERS IN PHYSIOLOGY, v. 8, JAN 23 2017. (10/02963-2, 16/16831-7)