The study also identified similar molecular patterns in human tissue, suggesting that important aspects of obesity-related nerve damage may occur in both mice and people. The findings were published in the journal Nature.

Obesity is known to affect much more than body weight and metabolism. It can alter immune activity, disrupt nerve structures, and reshape tissues throughout the body, increasing the risk of conditions such as type 2 diabetes, cardiovascular disease, stroke, neuropathy, and cancer. Despite these widespread effects, scientists have lacked tools capable of studying disease-related changes across an entire intact body in high detail.

To address that challenge, a research team led by Prof. Ali Ertürk, Director of the Institute for Biological Intelligence (iBIO) at Helmholtz Munich and Professor at LMU, developed MouseMapper. The AI framework uses foundation-model-based deep learning algorithms to analyze massive whole-body imaging datasets.

The system can automatically identify and segment 31 organs and tissue types while also mapping nerves and immune cells throughout the body. This allows researchers to examine how diseases affect multiple organ systems at the same time 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.

Transparent Mice and Whole-Body Imaging

To build the body maps, researchers first tagged nerves and immune cells in mice using fluorescent markers that glow under a microscope. They then used tissue-clearing methods to make the mice transparent while preserving the fluorescent signals, allowing scientists to see deep inside the body without cutting tissues apart.

Next, the team used advanced light-sheet microscopy to capture detailed three-dimensional images of entire mice. The process generated enormous datasets containing tens of millions of cellular structures from organs and tissues across the body.

MouseMapper then analyzed the images automatically, identifying anatomical regions, nerve networks, and immune-cell clusters throughout the animals.

This approach allowed the researchers to pinpoint exactly where inflammation and tissue damage appeared in organs such as fat tissue, muscle, liver, and peripheral nerves. Unlike earlier methods, scientists did not need to choose specific regions to study beforehand.

Obesity Linked to Facial Nerve Damage

To explore how obesity changes the body, the researchers fed mice a high-fat diet that produced obesity and metabolic problems similar to those seen in humans.

Using MouseMapper, the team found widespread alterations in immune-cell organization and nerve structures across the body. One of the most surprising discoveries involved the trigeminal nerve, a major facial nerve responsible for facial sensation and certain motor functions.

In obese mice, these sensory nerves showed a major reduction in branches and nerve endings, suggesting impaired nerve function. Behavioral tests supported that conclusion, showing that obese mice were less responsive to sensory stimulation compared to lean mice.

The researchers then focused on the trigeminal ganglion, which contains the cell bodies of facial sensory neurons. Through spatial proteomics analysis, they identified molecular changes linked to inflammation and nerve remodeling.

Importantly, many of the same molecular signatures were also found in trigeminal tissue from people with obesity. This suggests that the nerve-related changes observed in mice may 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 New Tool for Studying Complex Diseases

The researchers believe MouseMapper could become an important tool for studying diseases that affect many organ systems simultaneously, including diabetes, cancer, neurodegenerative diseases, and autoimmune disorders.

Unlike earlier approaches focused on individual tissues or organs, MouseMapper provides an integrated whole-body analysis system that can identify disease hotspots throughout an organism.

The team has also made the whole-body datasets publicly available online so researchers around the world can explore obesity-related changes across organs and tissues.

"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."

The work was supported by the European Research Council (Consolidator Grant CALVARIA to A. Ertürk; grant 949017 to M. Rohm), the German Research Foundation (DFG) under Germany's Excellence Strategy within the Munich Cluster for Systems Neurology (SyNergy, ID 390857198, EXC 2145), DFG SFB 1052 (A9) and TR 296 (P03), the Collaborative Research Centre CRC 1744, the German Federal Ministry of Education and Research (NATON collaboration, 01KX2121, and HIVacToGC), the Vascular Dementia Research Foundation, the Nomis Heart Atlas Project Grant (Nomis Foundation), the Else-Kröner-Fresenius-Stiftung, the Edith-Haberland-Wagner Stiftung, the Helmut Horten Foundation, the EFSD and Novo Nordisk A/S Programme for Diabetes Research in Europe (to D. Kaltenecker), and the China Scholarship Council (to Y. Chen).