Scientists have created the most detailed map to date of the human hypothalamus, a crucial brain region that regulates body weight, appetite, sleep, and stress.
HYPOMAP confirms the critical role of the hypothalamus in body-weight regulation and has already allowed us to identify new genes linked to obesity
Giles Yeo
Published today in Nature, this comprehensive resource, called HYPOMAP, provides an unparalleled view of the brain's appetite centre and promises to accelerate the development of treatments for obesity and diabetes.
The hypothalamus is often described as the brain's 'control centre', orchestrating many of the body's most vital processes. While much of our knowledge of the hypothalamus comes from animal studies, especially in mice, translating these findings to humans has long been a challenge. HYPOMAP bridges this gap by providing an atlas of the individual cells within the human hypothalamus. This resource not only charts over 450 unique cell types but also highlights key differences between the human and mouse hypothalamus - differences that have major implications for drug development.
"This is a game-changer for understanding the human hypothalamus," said Professor Giles Yeo, senior author of the study from the Institute of Metabolic Science-Metabolic Research Laboratories (IMS-MRL) and MRC Metabolic Diseases Unit, University of Cambridge.
"HYPOMAP confirms the critical role of the hypothalamus in body-weight regulation and has already allowed us to identify new genes linked to obesity. It gives us a roadmap to develop more effective, human-specific therapies."
Together with researchers at the Max Planck Institute for Metabolism Research in Cologne, Professor Yeo and colleagues used cutting-edge technologies to analyse over 400,000 cells from 18 human donors. HYPOMAP allows researchers to pinpoint specific cell types, understand their genetic profiles, and explore how they interact with neighbouring cells. This detailed cellular resolution offers invaluable insights into the circuits that regulate appetite and energy balance, as well as other functions such as sleep and stress responses.
Comparison with a mouse hypothalamus atlas revealed both similarities and critical differences. Notably, some neurons in the mouse hypothalamus have receptors for GLP-1 - targets of popular weight-loss drugs like semaglutide - that are absent in humans.
"While drugs like semaglutide have shown success in treating obesity, newer therapies target multiple receptors such as GLP-1R and GIPR. Understanding how these receptors function specifically in the human hypothalamus is now crucial for designing safer and more effective treatments," said Dr Georgina Dowsett from the Max Planck Institute for Metabolism Research and formerly at the IMS-MRL.
"Our map of the human hypothalamus is an essential tool for basic and translational research," added Professor Jens C. Brüning, Director at the Max Planck Institute. "It allows us to pinpoint which mouse nerve cells are most comparable to human cells, enabling more targeted preclinical studies."
HYPOMAP's open-access nature ensures that it will be an invaluable resource for scientists worldwide. By offering insights into the hypothalamus's role in conditions ranging from obesity to cachexia (a wasting condition associated with several illness, which involves extreme loss of muscle and fat), it provides a foundation for tackling some of the most pressing health challenges of our time.
Dr John Tadross, Consultant Pathologist at Addenbrooke's Hospital and lead author from IMS-MRL, said: "This is just the beginning. The atlas itself is a milestone, but what could really make a difference for patients is understanding how the hypothalamus changes in people who are overweight or underweight. This could fundamentally shift our approach to metabolic health and enable more personalised therapies."
With HYPOMAP, researchers have a new tool to unlock the secrets of the human brain's metabolic control centre. By better understanding the human hypothalamus, science takes a significant step toward combating obesity, diabetes, and related conditions.
Reference
Tadross, JA, Steuernagel, L & Dowsett, GKC et al. A comprehensive spatio-cellular map of the human hypothalamus. Nature; 5 Feb 2025; DOI: 10.1038/s41586-024-08504-8
Adapted from a story by the Institute of Metabolic Science-Metabolic Research Laboratories and the Max Planck Institute for Metabolism Research
