CBMR wins €2M ERC Consolidator grant to discover appetite-regulating signals from brown fat

The brain controls our appetite by judging our energy needs based on many signals released by organs in the body. When this feedback system is disrupted, it can lead to obesity, a growing public health threat that affects hundreds of millions of people around the world.

Scientists have already identified the energy-regulating signals released by a number of organs in the body, including white fat, the body’s long-term energy store. But little is known about the signals released by brown fat, a sub-type of fat that can burn energy and generate heat when the body is exposed to the cold.

This is the focus of a prestigious €2,000,000 (DKK 15M) Consolidator Grant from the European Research Council awarded to CBMR's Associate Professor Camilla Schéele.

Potential for a breakthrough in obesity research
Her project BALDER will attempt to identify previously unknown peptide signaling molecules that are released by brown fat to help the brain regulate feeding behavior. Driving the research is a hypothesis that brown fat releases different signals depending on its energetic state. It will be investigated if brown fat, when activated upon exposure to the cold, releases signals that increase appetite, and when deactivated releases signals to suppress appetite.

“With this proposal we will explore a new biology of a crosstalk between brown fat and brain, and by doing this, we have the potential for discovering novel peptides that regulate appetite and counteract obesity. This would be a breakthrough within obesity research and a major discovery that would be beneficial at multiple levels ranging from global health and economy to individuals’ well-being,” says Associate Professor Camilla Schéele.

The project has three stages. The first stage is to collect a library of human brown fat peptides that are released when brown fat is in different energetic states. The second stage will be to identify which peptides trigger a response in cell cultures of appetite-regulating brain cells. The final stage involves testing the successful candidates from the second stage on mice to understand what impact these peptides have on their metabolism.

ERC Consolidator grant – a recognition of research excellence
Camilla Schéele has progressed to the forefront of human brown fat research, since starting in the field in 2010. In 2013 she published a seminal paper in Cell Metabolism, providing molecular evidence for brown fat in adult humans and demonstrating for the first time that brown fat precursor cells could be isolated from adult humans.

Following her initial breakthrough, Camilla Schéele focused her attention on brown fat as a metabolic regulator. In a collaboration with Professor Matthias Mann from the Novo Nordisk Foundation Center for Protein Research (CPR), which was published in Cell Metabolism in 2019, she performed a secretomics map demonstrating that human brown and white fat cells talk different languages.

In February 2020, Camilla Schéele published a comprehensive review of brown fat signals, ‘batokines’, in Endocrine Reviews, together with Professor Christian Wolfrum from ETH Zürich. And in November 2020, she outlined the potential for research into the communication systems between the brain and brown fat in a review for the Annual Reviews of Physiology – ideas that support the hypothesis of the ERC Consolidator Grant.

A further significant contribution to the field includes a collaboration with Dr Denis Blondin and Professor André Carpentier from University of Sherbrooke that resulted in the discovery that human brown fat is targeted by a different receptor than in mice – the major model for brown fat research – which was published in Cell Metabolism in August 2020.  

Contact
Associate Professor Camilla Schéele
cs@sund.ku.dk