Effect of leukotrienes on the dioxin-induced obesity in 5-LO knockout mice: a proteomic study

• Grant number: 16/17783-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): January 01, 2017
• Effective date (End): December 31, 2017
• Field of knowledge: Biological Sciences - Pharmacology - Toxicology
• Principal Investigator: Camila Peres Buzalaf
• Grantee: Isadora de Oliveira Soler
• Host Institution: Pró-Reitoria de Pesquisa e Pós-Graduação. Universidade do Sagrado Coração (USC). Bauru , SP, Brazil

Abstract

Dioxins are persistent toxic pollutants in the environment and associated with various health problems to human health. Among several toxic effects, several studies have shown an association between exposure to these elements and the development of metabolic syndrome, a group of diseases associated with obesity such as type 2 diabetes. The decreased insulin sensitivity is a characteristic of this disease and they are a consequence of the presence of inflammatory cells and mediators in the adipose tissue and liver, among other factors. Among the different inflammatory mediators, we highlight the leukotrienes (LTs), substances produced from the enzyme 5-lipoxygenase (5-LO). It has been shown that the presence of LTs increases inflammatory responses and decreases insulin sensitivity. However, little is known about the contribution of LTs in determining obesity parameters and diabetes in mice exposed to dioxin and also the molecular mechanisms involved. The objective of this study is to evaluate the protein profiles of liver toxicity induced by in vivo exposure of LT-producing and LTs- non- producing mice to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which may be related to the lipid metabolism. Therefore, wild mice (WT 129-) and depleted the enzyme 5-LO (5-LO KO) will receive high calorie diet and TCDD concurrently for 30 days. After this period, the molecular mechanisms involved in toxicity will be assessed by label-free proteomic analysis of the liver in different experimental conditions. Thus, it is intended to identify the importance of LTs in mediating the toxic effect of TCDD on lipid metabolism as well as identifying proteins that may be targets of toxicity caused by such contaminants found in the environment, which the human population is exposed. (AU)