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

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)