A study published today in Nature reports the creation of the first detailed map of the human hypothalamus, a key part of the brain that contributes to obesity and weight management as part of its critical and diverse role in regulating metabolism, body weight, appetite, sleep and stress. Dr John Tadross, Molecular Pathology Lead for East Genomics and a researcher at the Institute of Metabolic Science-Metabolic Research Laboratories (IMS-MRL), University of Cambridge, played a key role in the research, as the study’s first author.
A map of metabolic regulation
The study presents a research tool called HYPOMAP (opens in a new tab) that is the first comprehensive cellular map of the human hypothalamus – a kind of “Google Maps” for the brain. It was developed in collaboration with the IMS-MRL and Max Planck Institute for Metabolism Research in Cologne and includes analysis of over 400,000 cells, across more than 450 cell types, from 18 human donors. It has the potential to reveal insights into the role of the hypothalamus in metabolic health as well as a range of metabolic diseases.
HYPOMAP represents a valuable new research resource, that incorporates spatial and gene expression data. The team have already used it to investigate the role of the hypothalamus in healthy metabolic regulation and have identified new genes linked to obesity. The hope now is to expand the map to explore how the hypothalamus may be affected by other metabolic conditions.
Read the paper in full (opens in a new tab) and the summary provided by Nature research briefings.
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.
Dr John Tadross, Molecular Pathology Clinical Co-lead at East Genomics
Translating research insights into humans
Much of what we know about the hypothalamus is the result of studies in animals, which are a close but imperfect approximation of human biology. HYPOMAP shows the importance of human-specific data by demonstrating the similarities and differences between humans and common animal models, which could inform future drug development. For example, certain cells that are receptive to popular weight loss drugs in mice, do not have the same sensitivity in humans.
This is a game-changer for understanding the human hypothalamus. 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.
Professor Giles Yeo, Institute of Metabolic Science-Metabolic Research Laboratories (IMS-MRL)
A resource for the scientific community
HYPOMAP has been made openly available as a resource to researchers. The team believe it has a key role to play in addressing several critical health challenges, and could offer key insights into the treatment and management of conditions including obesity and cachexia – also known as wasting syndrome or anorexia cachexia syndrome.
Our map of the human hypothalamus is an essential tool for basic and translational research. It allows us to pinpoint which mouse nerve cells are most comparable to human cells, enabling more targeted preclinical studies.
Professor Jens C. Brüning, Director at the Max Planck Institute
Impact on future healthcare
This research brings together cutting-edge science and patient-centred healthcare which is a key part of the NHS Genomic Medicine Service. By advancing our understanding of metabolic health and its genetic underpinnings, HYPOMAP could inform future clinical strategies, leading to improved therapies and outcomes for patients with obesity and related disorders.