Metabolic effects of omega-3 fatty acid in insulin resistance conditions

• Grant number: 11/09640-7
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: June 01, 2012
• End date: May 31, 2016
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Maria Cristina Foss de Freitas
• Grantee: Maria Cristina Foss de Freitas
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Diane Meyre Rassi ; Milton Cesar Foss ; Norma Tiraboschi Foss ; Patrícia Moreira Gomes ; Tiago Rosin Vidal ; Vivian Marques Miguel Suen

Abstract

A state of chronic inflammation and subclinical, often accompanies the excessive accumulation of lipids in adipose tissue and liver, as evidenced both by changes in inflammatory cells and by biochemical markers of inflammation and activation markers of endoplasmic reticulum stress (ERE). Previous studies have shown that polyunsaturated fatty acids n-3 (Omega-3) modulate gene expression of transcription factors such as NFkB and PPAR, which can contribute to reduce inflammation and insulin resistance (IR) in laboratory animals. However, it is not well characterized the effect of this fatty acid in the metabolic regulation of patients with RI. Thus, the objective of this study is to evaluate models of IR (type 2 diabetes mellitus (T2DM) and obesity) in humans and experimental studies in laboratory animals, the effect of treatment with Omega-3 in insulin sensitivity, in sub-clinical inflammatory process, control of glucose and lipid metabolism and activation of the ERE. As far as the human study with laboratory animals, people or animals will be allocated to one of the treatments, Omega-3 or placebo for a period of two months. Blood samples will be collected to measure plasma glucose and fasting insulin, glycated hemoglobin, lipid profile, measurement of C-reactive protein, cytokines and adipokines (TNF-±, IL-6, IL1², INF-³, MCP-1, leptin and adiponectin) before and after treatment. During bariatric surgery in obese patients or sacrifice of animals there will be collected biopsy of subcutaneous and visceral adipose tissue for evaluation of mRNA and proteins levels involved in processes of IR (IRS, insulin receptor, AKT), inflammation (NFºB, JNK, TNF- ±, IL-6, IL1², INF-³, MCP-1) and ERE (Bip, IRE1, PERK, XBP1 total and spliced, ATF4, ATF6±/²,, CHOP, HSP70 and HSF-1) using the techniques of Western blot, Eletrophoretic Mobility Shift Assay (EMSA) and real-time PCR. A better understanding of mechanisms of action of omega-3 will have a direct impact on the elucidation of metabolic processes related to insulin resistance in obesity and T2DM, as well as the development of new therapies. (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)

GOMES, PATRICIA M.; HOLLANDA-MIRANDA, WALLACE R.; BERALDO, REBECA A.; CASTRO, ANA V. B.; GELONEZE, BRUNO; FOSS, MILTON C.; FOSS-FREITAS, MARIA C.. Supplementation of alpha-linolenic acid improves serum adiponectin levels and insulin sensitivity in patients with type 2 diabetes. NUTRITION, v. 31, n. 6, p. 853-857, JUN 2015. (11/09640-7)

GONCALVES, NATALIA BONISSI; BANNITZ, RAFAEL FERRAZ; SILVA, BRUNA RAMOS; BECARI, DANIELLE DURAN; POLONI, CAROLINA; GOMES, PATRICIA MOREIRA; FOSS, MILTON CESAR; FOSS-FREITAS, MARIA CRISTINA. alpha-Linolenic acid prevents hepatic steatosis and improves glucose tolerance in mice fed a high-fat diet. Clinics, v. 73, 2018. (11/09640-7)

NATÁLIA BONISSI GONÇALVES; RAFAEL FERRAZ BANNITZ; BRUNA RAMOS SILVA; DANIELLE DURAN BECARI; CAROLINA POLONI; PATRÍCIA MOREIRA GOMES; MILTON CESAR FOSS; MARIA CRISTINA FOSS-FREITAS. α-Linolenic acid prevents hepatic steatosis and improves glucose tolerance in mice fed a high-fat diet. Clinics, v. 73, 2018-10-29. (11/09640-7)