Objective
This research addresses the question of how the manipulation of Keap1/Nrf2 signaling in adipose tissue affects the development of obesity and metabolic syndrome. Nrf2 is a central orchestrator of a battery of antioxidant and cytoprotective genes in response to oxidative or electrophilic stress and there is growing evidence that it cross-talks with other pathways. Our previous works showed that the whole body deletion of Nrf2 protected, at least partially, mice from high-fat diet (HFD)-induced obesity and insulin resistance and led to impaired adipogenesis. Another study has shown that mice treated with an Nrf2 activator, the triterpenoid CDDO-Im, were also protected from HFD-induced obesity. However, little is known about the exact mechanisms involved and which tissue is the main contributor to the resulting phenotype. Taking into account that there is in vitro evidence that Nrf2 is implicated in adipogenesis by crosstalking with transcription factors central to the adipocyte differentiation (PPARgamma, C/EBP beta), the main focus of this research will be to develop a murine model with conditional deletion of Nrf2 (loss of Nrf2 function) or Keap1 (gain of Nrf2 function) in adipose tissue using the Cre-recombinase-loxP system. Using both these models we will study how genetic manipulation of Nrf2 specifically in adipose tissue affects the development of HFD-induced obesity, the oxygen and energy consumption, the insulin resistance and the expression of genes involved in adipogenesis and lipid metabolism in adipose and other tissues in the different genotypes. Experiments using primary adipocyte cultures will give a mechanistic insight into adipogenesis and insulin signaling. This work will advance the field of obesity by actually being the first work that scrutinously characterize Nrf2 as a novel target for obesity prevention and treatment and possibly pave the way for relevant future clinical trials using Keap1/Nrf2 pathway modifying agents.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences medical biotechnology genetic engineering
- natural sciences biological sciences biochemistry biomolecules lipids
- medical and health sciences health sciences nutrition obesity
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2012-IOF
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Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
265 04 RIO PATRAS
Greece
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.