Project description
Examining the liver-fat interaction in MASLD
Metabolic dysfunction-associated steatotic liver disease (MASLD) affects one in four people worldwide, and it is driven largely by obesity. However, no approved treatments exist, partly because the biological mechanisms behind the disease remain elusive. Evidence points to complex interactions between the liver and visceral fat as key to disease progression. Supported by the Marie Skłodowska-Curie Actions programme, the XB-LIVAT project will combine 3D human liver spheroids and clinical fat tissue samples in an advanced co-culture model. This setup, enhanced by cutting-edge molecular analyses, aims to uncover how visceral fat contributes to disease development. By mapping the early molecular events and key cellular interactions, XB-LIVAT hopes to identify new therapeutic targets and reshape our understanding of liver disease.
Objective
With the obesity epidemic and prevalence of 25%, metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent liver disease in the world. Despite the enormous economic and clinical burden that MASLD poses, there are still no approved therapies. Mechanisms regulating disease progression are largely unknown, but the crosstalk of liver and visceral adipose tissue (VAT) in the context of obesity, appears to be instrumental in driving the onset of steatosis and progression to metabolic dysfunction associated steatohepatitis (MASH) and fibrosis. This is also due to the role that VAT has in mediating immune modulation, inflammatory and metabolic alterations. The hypothesis is that VAT-driven intercellular communication involving hepatocytes and liver non-parenchymal cells (NPCs), has a significant role in MASLD progression. To study the liver-VAT axis in vitro, it is of utmost importance to reproduce the complex and multicellular nature of these tissues. Contrary to previous studies based on simplistic two-dimensional co-cultures of single cell types, XB-LIVAT proposes to use a holistic, interdisciplinary and translational approach to study liver-VAT axis. XB-LIVAT will use a novel co-culture system consisting of an advanced human hetero-cellular liver three-dimensional spheroid model and clinical VAT explants, together with state-of-the-art ‘omics’ technologies to unravel key cell players, early molecular events, and targets in MASLD. In combination with in-depth molecular analysis of MASLD liver biopsies, this advanced in vitro co-culture model with high translational value will shed light on molecular mechanisms in MASLD, with particular focus on the role of NPCs. In addition to contributing to the discovery of novel therapeutic targets and interventional approaches for improving the clinical management of MASLD, XB-LIVAT will shape the researcher into an expert in advanced in vitro disease modeling and translational hepatology.
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 hepatology
- medical and health sciences health sciences nutrition obesity
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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)
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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
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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
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2024-PF-01
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34149 TRIESTE
Italy
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