Project description
A new dawn in anti-obesity drug development
Obesity, an escalating public health crisis, is accompanied by an alarming surge in chronic ailments such as diabetes, cardiovascular diseases, and cancer. The intricate control of energy balance, masterminded by the hypothalamus’ arcuate nucleus, plays a pivotal role. Yet, despite our knowledge of this central regulation, effective treatments have eluded us. With the support of the Marie Skłodowska-Curie Actions programme, the FEEDING project aims to better understand this complexity by venturing into the uncharted territory of orphan G protein-coupled receptors and their interaction with leptin receptors. Through the ingenious employment of knockout models, pharmacological agents, and metabolic assessments, scientists seek to crack the code of leptin resistance. This endeavour holds the potential to redefine the battle against obesity.
Objective
"Obesity is a major burden to public health as it increases the risk of several chronic diseases, like diabetes, cardiovascular diseases, musculoskeletal disorders or some cancers. Energy homeostasis is centrally regulated by the hypothalamus where the arcuate nucleus (ARC) orchestrates feeding behaviors and energy balance. Two neuronal populations of the ARC are considered as the first-order neurons mediating the effects of various signals such as leptin and insulin, the orexigenic neuropeptide (NP)Y/Agouti-related peptide (AgRP) neurons and the anorexigenic pro-opiomelanocortin (POMC)/Amphetamine-regulated transcript (CART) neurons. Leptin is an adipocyte-secreted peptidic hormone that inhibits food intake and regulates body weight. Nearly in all forms of obesity, circulating levels of leptin increase but fail to suppress food intake and body weight. This condition has been identified as ""leptin resistance"".
G protein-coupled receptors (GPCRs) are the largest family of membrane proteins and a notoriously successful source of drug targets. However, many GPCRs are understudied or even orphans meaning they have no known ligands. Despite our knowledge of the principal circuits regulating feeding, satiety, hunger and energy expenditure, we have been unable to deliver effective drugs targeting these systems. The failure in targeting the melanocortin pathways comes out partly from an incomplete understanding of leptin action, especially leptin resistance, at the central level. Here, we propose to investigate the interplay between the signaling of orphan GPCR and leptin receptor in leptin sensitive cells of the arcuate nucleus. To do so, we will use conditional knockout animals and pharmacological modulators. We will measure various metabolic parameters including weight and food intake with the Comprehensive Laboratory Animal Monitoring System (CLAMS). We will also establish hypothalamic cell cultures in which we will address the impact of G protein signaling on leptin."
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.
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine endocrinology diabetes
- medical and health sciences clinical medicine oncology
- medical and health sciences basic medicine physiology homeostasis
- 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)
MAIN PROGRAMME
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Topic(s)
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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
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.
4000 LIEGE
Belgium
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.