Effect of omega-3 fatty acids ingestion on expression and function of Toll-like receptors in peripheral blood mononuclear cells in obese subjects

• Grant number: 11/17774-3
• Support Opportunities: Scholarships abroad - Research
• Start date: April 23, 2012
• End date: February 01, 2013
• Field of knowledge: Agronomical Sciences - Food Science and Technology - Food Science
• Principal Investigator: Marcelo Macedo Rogero
• Grantee: Marcelo Macedo Rogero
• Host Investigator: Philip C. Calder
• Host Institution: Faculdade de Saúde Pública (FSP). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of Southampton, England

Abstract

Obesity has been characterized as a state of chronic inflammation. Emerging evidence over the past decade has shown that inflammation is one of the crucial mechanisms in the development of obesity-associated insulin resistance, type 2 diabetes and cardiovascular disease. In this context, activation of toll-like receptor signaling has been recognized as an alternative activator of obesity-induced inflammation. Epidemiological studies strongly suggest that omega-3 fatty acids have anti-inflammatory properties, and levels of these lipids in plasma, as well as in erythrocyte membrane, negatively correlate with plasma pro-inflammatory markers, including C-reactive protein and interleukin-6. We will examine the hypotheses that a) expression and function of toll-like receptors in peripheral blood mononuclear cells are upregulated in obese subjects and b) that n-3 fatty acids will lower the expression and function of toll-like receptors in peripheral blood mononuclear cells in obese subjects. Subjects aged 18 to 65 years with normal weight (a body mass index (BMI) between 18.5 and 25 kg/m2 (n = 50)) and obesity (BMI 30 to 40 kg/m2 (n = 50) and a waist circumference > 94 cm for men and > 80 cm for women) will be recruited. Subjects will be randomised to consume placebo or "fish oil" capsules daily for about 12 weeks. Approximately 1.8 g eicosapentaenoic acid plus docosahexaenoic acid will be given per day during the study. Cell surface expression of TLR2 and TLR4 will be assessed on peripheral blood mononuclear cells by flow cytometry. After culture, monocyte will be permeabilised and intracellularly stained with phycoerythrin- labelled monoclonal antibodies against cytokines IL-1², TNF± and IL-6. Concentrations of IL-1², IL-6, IL-8, IL-10, TNF± and IL-12p70 in the culture medium will be assayed by flow cytometry. The statistical analysis will involve the comparison of inflammatory markers and of expression and function of toll-like receptors in peripheral blood mononuclear cells between normal weight and obese subjects and between placebo and n-3 fatty acid treatments. All statistical comparisons will be performed at the end of the study using SPSS version 14. (AU)