Objective
The metabolic syndrome and its several manifestations have currently taken a tremendous toll on many aspects of society. Nonalcoholic fatty liver disease (NAFLD) is considered the liver component of the metabolic syndrome while atherogenic dyslipidaemia, and especially apolipoprotein B (ApoB)-containing lipoproteins, is considered the major causal mechanism in atherosclerosis initiation and progression. By employing novel humanized mouse models that can be rendered acutely dyslipidemic, we have already demonstrated that,
at the very onset of dyslipidemia, ApoB-containing lipoproteins interact with immune cells in the liver causing immune and metabolic changes, including ectopic lipid deposition. This opened to the idea that the inflammatory response evoked by acute dyslipidemia plays a pivotal role in the initiation of other important lipid-driven diseases such as NAFLD.
Hereafter, we present experiments to elucidate novel mechanisms central to the pathogenesis of NAFLD. We will better define the nature of the innate immune cells that firstly react to a dyslipidemic insult. This will be accomplished by imaging the different hepatic macrophage subsets after transition to dyslipidemia and by examining the physiological changes caused by liver Kupffer cells depletion. Secondly, we will investigate how this initial hepatic response will in turn affect atherosclerosis initiation and progression. We will target atherogenic factors secreted by liver immune cells upon ApoB uptake and inhibit several of them in vivo using neutralizing antibodies. Finally, by employing 2H2O to trace lipids' synthetic rates, we will clarify whether the hepatic lipid accumulation observed in our mice is of endogenous or exogenous sources. This project will yield powerful insights on targetable mechanisms concerning the initiation rather than the end-state of metabolic diseases that are currently endemic to the global population, opening to earlier detection and intervention.
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 clinical medicine cardiology cardiovascular diseases arteriosclerosis
- natural sciences biological sciences biochemistry biomolecules lipids
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
MAIN PROGRAMME
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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.
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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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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.
(opens in new window) HORIZON-MSCA-2022-PF-01
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
171 77 STOCKHOLM
Sweden
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.