Project description
A novel intervention against metabolic diseases
Adipose tissue communicates with the central nervous system through several different signaling pathways, including endocrine, paracrine and neural mechanisms. Leptin, an adipocyte-derived hormone, is one of the key signaling molecules that mediate this communication, acting on specific receptors in the hypothalamus of the brain that regulate energy homeostasis and feeding behaviour. Funded by the European Research Council, the HEAT-UP project will capitalise on the discovery of a leptin-independent signaling axis between adipose tissue and the central nervous system that decreases food intake and increases energy expenditure. Researchers will employ a selective agonist to the implicated receptor and investigate its impact on whole-body metabolism. Project findings will pave the way towards novel interventions for metabolic diseases.
Objective
Obesity and cardiometabolic diseases are global crises that threaten to cripple healthcare infrastructures. These disorders originate from an excess calorie burden caused by consuming too much food and expending too little energy. Yet despite recent advances in obesity drugs, weight-lowering pharmacotherapies only reach about half the efficacy of surgical interventions. This difference could be due to existing drugs only acting to reduce food intake and not boost calorie-burning. Therefore, I believe our discovery of a leptin-independent signaling axis between adipose tissue (AT) and the central nervous system (CNS) that both decreases food intake and increases energy expenditure poses a breakthrough in obesity research. We uncovered this axis through receptor profiling and human genetic association studies and engineered a highly selective agonist that significantly decreases bodyweight and improves glucose and lipid homeostasis in obese mice. Our preliminary data have already led to a spinout company. However, the physiological signaling mechanisms of this receptor in AT and the CNS that shape systemic energy balance through peripheral calorie-burning and central control of food intake remain unknown. Thus, in HEAT-UP, we will delineate AT and CNS receptor circuits with single cell resolution and functionally test this signaling in 3D cultures of mouse and human AT. Tissue-specific contributions to whole-body metabolism will be assessed by combining our proprietary, selective agonist with state-of-the-art viral, genetic, and surgical manipulation of the receptor and neuronal wiring in AT and the CNS. Viral and genetic cell-labeling strategies will be used to characterize novel secretory cells that we found in mouse and human AT to contain the ligand for this receptor. Collectively, these studies will provide a comprehensive, physiological overview of a previously unknown fat-brain signaling axis and insight into its potential for counteracting metabolic diseases.
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 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.1.1 - European Research Council (ERC)
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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.
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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.
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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) ERC-2022-COG
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1165 KOBENHAVN
Denmark
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