Estudio del papel de los leucotrienos en el desarrollo de las resistencia a la insulina y arteriosclerosis asociadas a la obesidad

  • Franckhauser-vogel , Sylvie Laure (Principal Investigator)
  • Elias Puigdomenech, Ivet (Investigator)
  • Muñoz Forero, Sergio Antonio (Investigator)

Project Details

Description

Objectives and methodology:
Obesity is a worldwide increasing problem and is a risk factor for insulin resistance, type 2 diabetes and atherosclerosis. However, mechanisms involved in the development of these complications remain unclear. It has been postulated that adipose tissue inflammation induced by obesity, characterized by adipose tissue macrophage infiltration and inflammatory cytokine secretiion, etither by adipocytes or macrophages, may play a role in the onset of insulin resistance and atherosclerosis during obesity. It has been observed that expression of the ALox5ap gene, coding for a key protein in leukotriene B\sub 4\nosub (LTB\sub 4\nosub ) synthesis, is increased in adipocytes from human patients with obesity and insuline resistance, and in adipose tissue from an obese ans insuline resistant transgenic mouse model. This project aims to study the effects of a primary alteration of LTB4 synthesis in adipocytes by using transgenic mice over-expressing ALox5ap cDNA under the control of an adipose-tissue specific promoter. Then transgenic mice will be generated. In these transgenic mice, we will test the hypothesis that an increase in Alox5ap expression leads to increased leukotriene synthesis and changes in adipose tissue metabolism, and to macrophage infiltration and increased release of inflammatory cytokines. Moreover, we will examine whether these mice develop insulin resistance and atherosclerosis. In this project, we will also study leukotriene pathway in obesity and insulin resistance mous models. Thus, we hypothesize that during obesity, a dysfunction in leukotriene pathway in adipose tissue may be a key point in the onset of insuline resistance and atherosclerosis and that advances in the knowledge of the mechanisms underlying these alterations will be very useful for the development of new approaches for the prevention and therapy of these complications.
StatusFinished
Effective start/end date16/10/0730/12/10

Funding

  • Instituto de Salud "Carlos III": €91,355.00

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