A 3D-map of the metabolic centre supports research into anti-obesity drugs
A high-resolution spatial map of the human hypothalamus makes it possible to identify specific cells, determine their exact location and analyse their neighbouring cells. The cell atlas, called Hypomap, developed by researchers at the Max Planck Institute for Metabolism Research in Cologne and the University of Cambridge, is being made available to the scientific community and could aid the development of new drugs to combat obesity and diabetes.
The Hypomap is a detailed map of the human hypothalamus.
© MPI f. Metabolism Research/ L. Steuernagel
The hypothalamus is a central region of the brain that controls vital functions such as sleep, body temperature, hunger and thirst. Because the human brain is difficult to study, much knowledge about the hypothalamus is based on studies in mice and forms the basis for research on anti-obesity drugs. "We know that so-called GLP-1 agonists such as semaglutide help in humans, but to understand exactly how they work and possibly reduce side effects, we need to get to know the human hypothalamus better," explains Lukas Steuernagel, one of the authors of the study.
Combining their own data with information from the Human Cell Atlas, the researchers analysed a total of eleven human brains. They created a detailed map of the hypothalamus, showing where each cell is located and which genes are expressed in it at the level of individual cells. Using Hypomap, they were able to learn more about the neurons and circuits that regulate appetite and food intake, and identify cells that respond to new classes of drugs for diabetes and obesity.
Comparison of mouse and human brain
Comparison with a mouse cell atlas shows that the human and mouse hypothalamus have similarities, but also important differences. For example, some mouse neurons have receptors for GLP-1 that are absent in humans. "Our map of the human hypothalamus is crucial for basic research. We can now specifically analyse the nerve cells in the mouse brain that are also found in humans," explains Jens C. Brüning, Director at the Max Planck Institute for Metabolism Research. Giles Yeo, another study leader, points out: "Hypomap confirms what we knew about the important role of the brain in the control of body-weight, and has also allowed us to identify new genes linked to obesity."
The cell atlas will be made available to the research community and will be a valuable resource for drug development and further studies. "This is a huge milestone but we've still got a long way to go. The atlas itself is of great value, the vital next steps are to understand how the hypothalamus changes in individuals who are overweight or underweight," said John A. Tadross, one of the lead researchers from the University of Cambridge. "This knowledge could transform our understanding of metabolic health and help us target therapies more effectively."
