HEAT-UP
Financiado
Harnessing an energy-expending, appetite-suppressing fat-brain axis to unlock no...
Harnessing an energy-expending, appetite-suppressing fat-brain axis to unlock novel pharmacotherapies
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....
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.
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Duración del proyecto: 65 meses
Fecha Inicio: 2023-03-02
Fecha Fin: 2028-08-31
Fecha Fin: 2028-08-31
Línea de financiación: concedida
El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2023-03-02
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-2022-COG:
ERC CONSOLIDATOR GRANTS
Cerrada
hace 2 años
Presupuesto
El presupuesto total del proyecto asciende a
2M€
Líder del proyecto
KOBENHAVNS UNIVERSITET
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5