ERC awards grant to counteract metabolic diseases

The European Research Council has awarded the ERC Consolidator Grant to Associate Professor Zach Gerhart-Hines from the Novo Nordisk Foundation Center for Metabolic Research at the University of Copenhagen.

Over the next five years, Zach Gerhart-Hines will receive EUR 2 € million for his groundbreaking research project to deliver a comprehensive, physiological overview of a previously unknown fat-brain signaling axis and insight into its potential for counteracting metabolic diseases.

When talking about the biggest health crisis of our time, obesity and type 2 diabetes are among the top contenders that threaten to cripple healthcare infrastructures.

Yet despite recent pharmaceutical leaps, current drug treatments does not match surgical interventions like gastric bypass and tend to elicit undesirable effects, such as nausea, explains Zach Gerhart-Hines.

“These disorders originate from an excess calorie burden caused by consuming too much food and expending too little energy. Our chief goal is to learn more about how the metabolism of our fat tissue is coordinated with our desire to eat, which is controlled by the brain, to ensure healthy energy balance. In our project, HEAT-UP, we will additionally explore the therapeutic potential of targeting this fat tissue-brain axis to safely increase calorie-burning and decrease appetite without nausea. By doing so, we hope to provide a powerful new option for glucose control and weight loss for individuals living with type 2 diabetes and obesity,” he says.

Discovery poses a breakthrough in obesity research

Despite recent advances in obesity drugs, weight-lowering pharmacotherapies are still not able to achieve the efficacy of surgical interventions, especially in individuals living with both obesity and type 2 diabetes.

“This difference could be due to existing drugs only acting to reduce food intake and not boosting 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 increases energy expenditure  and decreases food intake, respectively, poses a breakthrough in obesity and type 2 diabetes research,” says Zach Gerhart-Hines.

“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. 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.

In HEAT-UP, the research team 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 their proprietary, selective agonist with state-of-the-art viral, genetic, and surgical manipulation of the receptor and neuronal wiring in AT and the CNS.

“The ERC Consolidator Grant is not only a personal career milestone but is also a validation and recognition of the extraordinary efforts put forward by our team. The inspiring group of scientists with whom I work are the primary reason this grant was achievable,” says Zach Gerhart-Hines.