Obesity affects far more than metabolism and fat storage. It alters immune activity, nerve structure, and tissue organization across multiple organ systems, increasing the risk of diseases including type 2 diabetes, cardiovascular disease, stroke, neuropathy and cancer. Yet despite these systemic effects, researchers have lacked tools capable of studying disease-associated changes across the entire body in intact organisms and at high resolution.
A team led by Prof. Ali Ertürk, Director of the Institute for Biological Intelligence (iBIO) at Helmholtz Munich and Professor at the LMU, has now developed MouseMapper, a suite of foundation-model-based deep-learning algorithms designed to analyze whole-body biological imaging data. The framework automatically segments 31 organs and tissue types while quantitatively mapping nerves and immune cells throughout the body, enabling comprehensive multi-system analysis in intact mice.
“MouseMapper is built on a foundation model, which means it generalizes far beyond the data it was originally trained on,” says Ying Chen, co-first author of the study.
Looking inside an entire transparent mouse
To create whole-body maps, the researchers labeled nerves and immune cells in mice with fluorescent markers visible under the microscope. They then used tissue-clearing techniques to render the animals transparent while preserving the fluorescent signals, allowing imaging deep inside intact bodies.
Using specialized light-sheet microscopy, the team captured detailed three-dimensional images of entire mice, producing datasets containing tens of millions of cellular structures across organs and tissues. MouseMapper then analyzed these data automatically, identifying nerves, immune-cell clusters, and anatomical regions throughout the body.
This allowed the researchers to determine precisely where inflammation and structural damage occur across different tissues – including fat, muscle, liver, and peripheral nerves – without requiring researchers to preselect specific regions of interest.
New insights into obesity, from mouse to human
To investigate how obesity reshapes the body, the researchers fed mice a high-fat diet that induced obesity and metabolic dysfunction similar to that observed in humans. Applying MouseMapper revealed widespread changes in both immune-cell organization and nerve architecture across the body.
One of the most striking findings was a structural change to part of the trigeminal nerve, a major facial nerve that is responsible for facial sensation and motor functions. In obese mice, these sensory nerves had far fewer endings and branches, suggesting a loss of normal nerve function. Behavioral experiments further showed that the animals responded less to sensory stimulation than lean mice, linking the structural damage to impaired sensory function.
The researchers next examined the trigeminal ganglion, the structure containing the cell bodies of facial sensory neurons. Using spatial proteomics, they identified molecular alterations associated with nerve remodeling and inflammation. Remarkably, many of the same molecular signatures were also detected in trigeminal tissue from people with obesity, suggesting that the obesity-associated nerve alterations observed in mice also occur in humans.
“We revealed previously unknown structural and molecular changes in the trigeminal ganglion and its facial branches, and the same molecular signature was conserved in human tissue. This kind of finding simply cannot emerge from studying one organ at a time” says Dr. Doris Kaltenecker, senior scientist at the Institute for Diabetes and Cancer (IDC) at Helmholtz Munich and first author of the study.
A platform for studying systemic disease
Beyond obesity, the researchers believe MouseMapper could transform the study of complex diseases that affect multiple organs systems simultaneously, including diabetes, cancer, neurodegeneration and autoimmune disorders. Unlike earlier methods focused on selected organs or tissues, MouseMapper provides an integrated whole-body analysis platform capable of identifying disease “hotspots” throughout the organism.
The team has made whole-body datasets publicly available online, allowing scientists worldwide to explore obesity-associated changes across tissues and organ systems.
“Our goal is to create a comprehensive framework for understanding how diseases affect the body as an interconnected system,” says Ali Ertürk. “Our long-term vision is to build truly realistic digital twins of mice in health and disease: cell-level atlases that we can query, perturb and screen in silico computationally. That would let us pinpoint the earliest changes a disease causes, design interventions to prevent them, and accelerate the discovery of new treatments while reducing the number of physical experiments we need to run.”
Original publication:
Kaltenecker, Horvath, Al-Maskari, Chen, Kolabas et al., 2026: A deep-learning framework reveals whole-body perturbations at cell level. Nature. DOI: 10.1038/s41586-026-10535-2
Helmholtz Munich is a leading biomedical research center. Its mission is to develop breakthrough solutions for better health in a rapidly changing world. Interdisciplinary research teams focus on environmentally triggered diseases, especially the therapy and prevention of diabetes, obesity, allergies, and chronic lung diseases. With the power of artificial intelligence and bioengineering, researchers accelerate the translation to patients. Helmholtz Munich has more than 2,550 employees and is headquartered in Munich/Neuherberg. It is a member of the Helmholtz Association, with more than 46,000 employees and 18 research centers the largest scientific organization in Germany. More about Helmholtz Munich (Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt GmbH): www.helmholtz-munich.de/en
The German Center for Diabetes Research (DZD e.V.) is one of the eight German Centers for Health Research. It brings together experts in the field of diabetes research and combines basic research, epidemiology and clinical application. The aim of the DZD is to make a significant contribution to the successful, customized prevention, diagnosis and treatment of diabetes mellitus through a novel, integrative research approach. www.dzd-ev.de/en
